Improving Diabetes Research: Moving Beyond Animal Models. Charu Chandrasekera, Ph.D. Anne Bunner, Ph.D.

Save this PDF as:
 WORD  PNG  TXT  JPG

Size: px
Start display at page:

Download "Improving Diabetes Research: Moving Beyond Animal Models. Charu Chandrasekera, Ph.D. Anne Bunner, Ph.D."

Transcription

1 Improving Diabetes Research: Moving Beyond Animal Models Charu Chandrasekera, Ph.D. Anne Bunner, Ph.D. July 19, 2014

2 From Bench-to-Bedside Sulfonylurea Biguanide Dipeptidyl peptidase-4 inhibitor Glucagon-like peptide-1 receptor agonist

3 From Bench-to-Bedside Januvia DPP- 4 GLP-1 Victoza GLP-1 PI3K Akt Rap Erk1/2 Glyburide Insulin Secretion Pancreatic β-cell

4 Type 2 Diabetes Research 1. Animal models of human type 2 diabetes 2. Limitations of animal models 3. Humanizing type 2 diabetes research

5 1. Animal Models of Type 2 Diabetes in Basic Research

6 Animal Models of Diabetes

7 Deciphering Diabetes The Problem Research Questions: - How? - What? - Why? - Why not? - When? The Solution! - Where? - What else?

8 Rodent Models this is how we do it

9 Rodent Models: Surgical Induction Non-obese diabetic model Partial (10 90%) or Complete pancreatectomy Extent of pancreatectomy governs severity of disease

10 Rodent Models: Chemical Induction Streptozotocin Glucose GLUT2 Irreversible β-cell cytotoxicity Non-obese model Dosage governs severity of disease Alloxan

11 Rodent Models: Dietary Modification Cafeteria Diet

12 Rodent Models: Dietary Modification Pre-Defined High-Fat Diets 30% 20% Fat content 50% 40% 70% 60% Fat types Olive oil Butter Coconut oil Fish oil Lard Beef tallow Vegetable shortening Obese diabetic models Diet type influences disease phenotype Other Components High Sucrose High Fructose Protein Micronutrients

13 Rodent Models: Genetic Models Obese diabetic models Naturally occurring Spontaneous Genetic Models Leptin and leptin receptor mutations e.g., ob/ob mouse, db/db mouse, Zucker fatty rat, Zucker diabetic fatty rat

14 Rodent Models: Genetic Models Knock-out Genetically Engineered Models Obese & non-obese Disease severity depends on genetic alteration Knock-in Transgenic

15 Rodent Models of Diabetes > 50 publications / month Chandrasekera et al. ALTEX 2014; 31: ob/ob db/db ZDF Other Rats Spontaneously Chemical Transgenic Diabetic Dietary Surgical

16 2. Limitations of Animal Models

17 Deciphering Diabetes In order for a rodent model to have relevance to human diabetes, it should display causes natural history pathophysiology manifestations complications drug responses in a manner similar to what is observed in humans.

18 Deciphering Diabetes Human T2DM = multifactorial & complex Type 2 Diabetes

19 Of Rodents and Men 1. Experimental Limitations 2. Biological Limitations 3. Species Differences

20 1. Experimental Limitations: Surgical Induction Sudden pancreatic loss Extent governs disease severity e.g., 80% resection gives mild hyperglycemia β-cell regeneration & full recovery Loss of counter-regulation e.g., glucagon Chandrasekera et al. ALTEX 2014; 31:157-76

21 1. Experimental Limitations: Chemical Induction Dosage dependence Streptozotocin Extrapancreatic cytotoxic effects e.g., disruption of the HPG axis Human β-cells resistant to streptozotocin in rodents, enter cells via GLUT2 GLUT1 GLUT3 Chandrasekera et al. ALTEX 2014; 31:157-76

22 1. Experimental Limitations: Dietary Induction Diet type Diet components Control diet Age of onset of diet Duration of diet Lai et al. Nutr Diabetes, 2014

23 1. Experimental Limitations: Genetic Induction Leptin mutations rare in humans Wang et al. Curr Diab Rev. 2014; 10: Single-gene effect Exaggerated & compensatory effects Developmental defects Bunner et al. World J Diab. 2014; 5:

24 2. Biological Limitations Age young adult old Sex No disease phenotype Prominent disease phenotype Strain C57BL/6J, AKR/J, FVB/N, 129SeVe

25 2. Biological Limitations Heterogeneity among strains 60% weight gain Heterogeneity within one strain 30% weight gain 10% weight gain Control High Fat Diet Weight gain Plasma glucose Plasma insulin Serum lipid Glucose tolerance

26 2. Biological Limitations Health of laboratory animals is poor by human standards Control laboratory rodents are metabolically morbid: why it matters Obese Insulin resistant Hypertesive On a trajectory to premature death profound differences in experimental outcome confound data interpretation and outcomes of human studies Martin et al. PNAS 2010; 107:

27 Chandrasekera et al. ALTEX 2014; 31: Species Differences

28 3. Species Differences

29 3. Species Differences α δ β

30 3. Species Differences

31 Critiques of Rodent Models Of rodents and men: species specificity of glucose regulation and type 2 diabetes research. Chandrasekera et al. ALTEX 2014; 31(2): Leptin- and leptin receptor-deficient rodent models: relevance for human type 2 diabetes. Wang et al. Curr Diab Rev. 2014; 10(2): Knockout mouse models of insuling signaling: relevance past and future. Bunner et al. World J Diabetes. 2014; 5(2): You are what you eat, or are you? The challenges of translating high-fatfed rodents to human obesity and type 2 diabetes. Lai et al. Accepted for publication in Nutrition & Diabetes, 2014 From animal models to clinical practicality: lessons learned from current translational progress of diabetic peripheral neuropathy. Li et al. In: Souayah N, ed. Peripheral Neuropathy - A New Insight into the Mechanism, Evaluation and Management of a Complex Disorder. New York, NY 2013.

32 Limitations of Rodent Models: The Case of ZnT8 Zn 2+ insulin secretory granules ZnT8 zinc transporter Genetic study in a small French population identified novel risk loci for T2D: Sladek et al. Nature 2007; 445: insulin secretory granules

33 Limitations of Rodent Models: The Case of ZnT8 ZnT8 zinc transporter ZnT8 Gene Deletion ZnT8 Knockout

34 Limitations of Rodent Models: The Case of ZnT8

35 Limitations of Rodent Models: The Case of ZnT8 ZnT8 Knockout Variability Age Sex Strain Weight gain Blood glucose Plasma insulin Glucose tolerance Insulin secretion Diet Disease Severity No Change Significant Increase Marked Reduction

36 Limitations of Rodent Models: The Case of ZnT8 Pound et al. PLoS One 2012; 7:e40972

37 Limitations of Rodent Models: The Case of ZnT8 intriguing differences between the phenotypes of the animal models 150,000 humans with protein-truncating mutations loss of ZnT8 increased disease risk loss of ZnT8 reduced disease risk Rutter GA. Islets 2010; 2: Flannnick et al. Nat Genet 2014; 46:

38 Limitations of Rodent Models causes natural history pathophysiology manifestations complications drug responses

39 Deciphering Diabetes NOT The Solution! The Problem

40 3. Human-based Methods

41

42 Human Data Modeling complex interactions in silico Algorithms for pancreas function were used to develop a closedloop insulin pump. Kovatchev B, et al. (2009) J Diabetes Sci Technol 3, Kovatchev B, et al. (2010) J Diabetes Sci Technol 4,

43 Genome-Wide Association Studies Patients Nonpatients Disease-specific markers Patient DNA Compare differences to discover genetic markers associated with diseases Non-patient DNA Non-disease markers

44 Human Populations Population-based studies reveal genetic and environmental factors.

45 Odds Ratio Dietary factors AHS-2 study 41,000 people asked about diets and health Followed for 2 years Diabetes Incidence * * * * 95% CI shown Tonstad S, et al. (2013) Nutr Metab Cardiovasc Dis 23,

46 Human Beings Safe and ethical PET and functional MRI can be used to monitor glucose and insulin in volunteers. Bertoldo A, et al. (2006) Diabetes 55, Tesfaye and Selvarajah (2012) Diab/Metab Res Rev 28, S8-S14. Kullmann, et al. (2012) Human Brain Mapping 33,

47 GLP-1 and insulin secretion Glucagon-like peptide 1 (GLP-1) is a peptide important for normal glucose tolerance Victoza is a GLP-1 agonist Does GLP-1 work the same way in diabetes patients as in healthy volunteers? Drug that temporarily blocks GLP-1 activity drug Healthy volunteers drug Type 2 Diabetes patients GLP-1 GLP-1 Insulin secretion Insulin secretion Salehi M, et al. (2010) Diabetes 59,

48 Human Organs Microfluidic systems mimic architecture of tissues and organs Commercially available liver cells

49 Human Tissues Tissues from: cadavers surgical patients

50 Human islets for drug screening Cultured human islets from cadavers Islets produced insulin in response to glucose Islets exposed to 1,280 compounds Used automated technology to detect changes in insulin secretion Functional cultured islets indicated by white arrowheads Walpita D, et al. (2012) J Biomol Screen 17,

51 Human islets for drug screening Functional cultured islets indicated by white arrowheads Walpita D, et al. (2012) J Biomol Screen 17,

52 Human Cells A human pancreatic β- cell line is now available for insulin secretion studies. Ravassard P, et al. (2011) J Clin Invest 121,

53 Inflammation and insulin resistance in human skeletal muscle How does inflammation contribute to insulin resistance? What genes are involved? Researchers used muscle cells from volunteers Turned off a certain gene in some samples to observe differences in response Stimulus Signaling protein Austin RL, et al. (2008) Diabetes 57, Insulin resistance Bouzakri K and Zierath JR (2007) J Biol Chem 282,

54 Many options for human studies Human studies are: Reliable Relevant Practical

55 Thank you for your attention! Questions?

NIH Public Access Author Manuscript Diabetologia. Author manuscript; available in PMC 2014 February 01.

NIH Public Access Author Manuscript Diabetologia. Author manuscript; available in PMC 2014 February 01. NIH Public Access Author Manuscript Published in final edited form as: Diabetologia. 2013 February ; 56(2): 231 233. doi:10.1007/s00125-012-2788-6. Lipotoxicity impairs incretin signalling V. Poitout 1,2

More information

Personalized therapeutics in diabetes

Personalized therapeutics in diabetes Personalized therapeutics in diabetes Leen M. t Hart Molecular Cell Biology & Molecular Epidemiology Leiden University Medical Center Epidemiology & Biostatistics VU University Medical Center Diabetes

More information

Diabetes: What is the scope of the problem?

Diabetes: What is the scope of the problem? Diabetes: What is the scope of the problem? Elizabeth R. Seaquist MD Division of Endocrinology and Diabetes Department of Medicine Director, General Clinical Research Center Pennock Family Chair in Diabetes

More information

DEVELOPMENT OF NEW ANIMAL MODELS FOR TYPE 2 DIABETES MELLITUS AND PHARMACOLOGICAL SCREENING

DEVELOPMENT OF NEW ANIMAL MODELS FOR TYPE 2 DIABETES MELLITUS AND PHARMACOLOGICAL SCREENING 2) LITERATURE REVIEW 1. Srinivasan et al., (2005) developed a new rat model that replicates the natural history and metabolic characteristics of human type 2 diabetes and is also suitable for pharmacological

More information

The uses of animal models in the evaluation of functional foods

The uses of animal models in the evaluation of functional foods The uses of animal models in the evaluation of functional foods Jane Chao, Ph.D. Taipei Medical University School of Nutrition and Health Sciences November 30, 2006 1 Content Assessments for health claims

More information

My Journey in Endocrinology. Samuel Cataland M.D

My Journey in Endocrinology. Samuel Cataland M.D My Journey in Endocrinology Samuel Cataland M.D. 1968-2015 Drs Berson M.D. Yalow phd Insulin Radioimmunoassay Nobel Prize Physiology or Medicine 1977 Rosalyn Yalow: Radioimmunoassay Technology Andrew Schally

More information

A Central Role of MG53 in Metabolic Syndrome. and Type-2 Diabetes

A Central Role of MG53 in Metabolic Syndrome. and Type-2 Diabetes A Central Role of MG53 in Metabolic Syndrome and Type-2 Diabetes Yan Zhang, Chunmei Cao, Rui-Ping Xiao Institute of Molecular Medicine (IMM) Peking University, Beijing, China Accelerated Aging in China

More information

Animal Models of Diabetes and Insulin Resistance. Masakazu Shiota, D.V.M., Ph.D An Organ System.. Course. July 18, 2012

Animal Models of Diabetes and Insulin Resistance. Masakazu Shiota, D.V.M., Ph.D An Organ System.. Course. July 18, 2012 Animal Models of Diabetes and Insulin Resistance Masakazu Shiota, D.V.M., Ph.D An Organ System.. Course. July 18, 2012 What is different between human and animals? mouse rat dog human What is different

More information

Obese Type 2 Diabetic Model. Rat Model with Early Onset of Diabetic Complications. SDT fatty rats. SDT fatty rats

Obese Type 2 Diabetic Model. Rat Model with Early Onset of Diabetic Complications. SDT fatty rats. SDT fatty rats Obese Type 2 Diabetic Model rats Rat Model with Early Onset of Diabetic Complications rats Background and Origin In 24, Dr. Masuyama and Dr. Shinohara (Research Laboratories of Torii Pharmaceutical Co.,

More information

Obesity in aging: Hormonal contribution

Obesity in aging: Hormonal contribution Obesity in aging: Hormonal contribution Hormonal issues in obesity and aging Hormonal role in regulation of energy balance Genetic component in hormonal regulation Life style contribution to hormonal changes

More information

IDF Regions and global projections of the number of people with diabetes (20-79 years), 2013 and Diabetes Atlas -sixth Edition: IDF 2013

IDF Regions and global projections of the number of people with diabetes (20-79 years), 2013 and Diabetes Atlas -sixth Edition: IDF 2013 IDF Regions and global projections of the number of people with diabetes (20-79 years), 2013 and 2035 Diabetes Atlas -sixth Edition: IDF 2013 Diabetes Atlas -sixth Edition: IDF 2013 Chronic complications

More information

SUPPLEMENTARY INFORMATION

SUPPLEMENTARY INFORMATION SUPPLEMENTARY INFORMATION doi:10.1038/nature11464 Supplemental Figure S1. The expression of Vegfb is increased in obese and diabetic mice as compared to lean mice. a-b, Body weight and postprandial blood

More information

The Atoms of Life. What are other elements would you expect to be on this list? Carbon Hydrogen Nitrogen Oxygen Phosphorous Sulfur (sometimes)

The Atoms of Life. What are other elements would you expect to be on this list? Carbon Hydrogen Nitrogen Oxygen Phosphorous Sulfur (sometimes) Macromolecules The Atoms of Life The most frequently found atoms in the body are Carbon Hydrogen Nitrogen Oxygen Phosphorous Sulfur (sometimes) What are other elements would you expect to be on this list?

More information

Metabolic Disease drug discovery at Evotec

Metabolic Disease drug discovery at Evotec Metabolic Disease drug discovery at Evotec Evotec, Metabolic Disease Drug Discovery, 2016 Evotec, an ideal partner in metabolic disease drug discovery The different ways to work with us On your specific

More information

HOW TO DEFINE GOOD BIOMARKERS OF HEALTH? Suzan Wopereis

HOW TO DEFINE GOOD BIOMARKERS OF HEALTH? Suzan Wopereis HOW TO DEFINE GOOD BIOMARKERS OF HEALTH? Suzan Wopereis My personal objective: identification of biomarkers of (optimal) health Biomarker Definition: a characteristic that is objectively measured and evaluated

More information

Targeting simultaneously GLP-1, GIP and glucagon receptors : a new paradigm for treating obesity and diabetes

Targeting simultaneously GLP-1, GIP and glucagon receptors : a new paradigm for treating obesity and diabetes SHORT COMMENT FOR NATURE REVIEWS ENDOCRINOLOGY Targeting simultaneously GLP-1, GIP and glucagon receptors : a new paradigm for treating obesity and diabetes André J. SCHEEN (1), Nicolas PAQUOT (2) (1)

More information

Week 3, Lecture 5a. Pathophysiology of Diabetes. Simin Liu, MD, ScD

Week 3, Lecture 5a. Pathophysiology of Diabetes. Simin Liu, MD, ScD Week 3, Lecture 5a Pathophysiology of Diabetes Simin Liu, MD, ScD General Model of Peptide Hormone Action Hormone Plasma Membrane Activated Nucleus Cellular Trafficking Enzymes Inhibited Receptor Effector

More information

DIABETES RESEARCH A CLINICIAN S OVERVIEW

DIABETES RESEARCH A CLINICIAN S OVERVIEW DIABETES RESEARCH 2012- A CLINICIAN S OVERVIEW Alan B. Cortez, MD Chief, Pediatrics Pediatric Endocrinology Kaiser-Permanente Orange County January 21, 2012 Research Overview Biotechnology Treatment Pharmaceutical

More information

Insulin resistance and pancreatic b cell failure

Insulin resistance and pancreatic b cell failure Review series introduction Insulin resistance and pancreatic b cell failure Masato Kasuga Department of Clinical Molecular Medicine, Kobe University Graduate School of Medicine, Kobe, Japan. It is now

More information

Unmasking the evidence of efficacy and safety. Cheaper or Better DEBATE (pros) Panagiotis Halvatsiotis

Unmasking the evidence of efficacy and safety. Cheaper or Better DEBATE (pros) Panagiotis Halvatsiotis Unmasking the evidence of efficacy and safety. Cheaper or Better DEBATE (pros) Panagiotis Halvatsiotis 2 nd Department of Internal Medicine Research Unit & Diabetes Center of Athens University Medical

More information

Society for Ambulatory Anesthesia Consensus Statement on Perioperative Blood Glucose Management in Diabetic Patients Undergoing Ambulatory Surgery

Society for Ambulatory Anesthesia Consensus Statement on Perioperative Blood Glucose Management in Diabetic Patients Undergoing Ambulatory Surgery Society for Ambulatory Anesthesia Consensus Statement on Perioperative Blood Glucose Management in Diabetic Patients Undergoing Ambulatory Surgery Girish P. Joshi, MB BS, MD, FFARCSI Anesthesia & Analgesia

More information

FOR REVIEW. BMB Reports - Manuscript Submission. Manuscript Draft. Manuscript Number: BMB

FOR REVIEW. BMB Reports - Manuscript Submission. Manuscript Draft. Manuscript Number: BMB BMB Reports - Manuscript Submission Manuscript Draft Manuscript Number: BMB-18-095 Title: Insulin Receptor Substrate 2:A Bridge between Hippo and AKT Pathways Article Type: Perspective (Invited Only) Keywords:

More information

Body Mass Index Chart = overweight; = obese; >40= extreme obesity

Body Mass Index Chart = overweight; = obese; >40= extreme obesity Pathophysiology of type 2 diabetes mellitus R. Leibel Naomi Berrie Diabetes Center 25 February 2008 Body Mass Index Chart 25-29.9 = overweight; 30-39.9= obese; >40= extreme obesity 5'0" 5'2" Weight (lbs)

More information

DIABETES. Mary Bruskewitz APNP, MS, BC-ADM Clinical Nurse Specialist Diabetes. November 2013

DIABETES. Mary Bruskewitz APNP, MS, BC-ADM Clinical Nurse Specialist Diabetes. November 2013 DIABETES Mary Bruskewitz APNP, MS, BC-ADM Clinical Nurse Specialist Diabetes November 2013 mbruskewitz@outlook.com Objectives Part 1 Overview of Endocrine Physiology Pathophysiology of Diabetes Diabetes

More information

What systems are involved in homeostatic regulation (give an example)?

What systems are involved in homeostatic regulation (give an example)? 1 UNIVERSITY OF PNG SCHOOL OF MEDICINE AND HEALTH SCIENCES DIVISION OF BASIC MEDICAL SCIENCES DISCIPLINE OF BIOCHEMISTRY AND MOLECULAR BIOLOGY GLUCOSE HOMEOSTASIS (Diabetes Mellitus Part 1): An Overview

More information

Multiple Factors Should Be Considered When Setting a Glycemic Goal

Multiple Factors Should Be Considered When Setting a Glycemic Goal Multiple Facts Should Be Considered When Setting a Glycemic Goal Patient attitude and expected treatment effts Risks potentially associated with hypoglycemia, other adverse events Disease duration Me stringent

More information

Journal Club WS 2012/13 Stefanie Nickl

Journal Club WS 2012/13 Stefanie Nickl Journal Club WS 2012/13 Stefanie Nickl Background Mesenchymal Stem Cells First isolation from bone marrow 30 ys ago Isolation from: spleen, heart, skeletal muscle, synovium, amniotic fluid, dental pulp,

More information

Pathogenesis of Type 2 Diabetes

Pathogenesis of Type 2 Diabetes 9/23/215 Multiple, Complex Pathophysiological Abnmalities in T2DM incretin effect gut carbohydrate delivery & absption pancreatic insulin secretion pancreatic glucagon secretion HYPERGLYCEMIA? Pathogenesis

More information

Voglibose, an Alpha-glucosidase Inhibitor, to Increase Active Glucagon-like Peptide-1 Levels

Voglibose, an Alpha-glucosidase Inhibitor, to Increase Active Glucagon-like Peptide-1 Levels PharmSight TM DOI: 10.4255/mcpharmacol.09.22 Molecular and Cellular Pharmacology www.mcpharmacol.com Voglibose, an Alpha-glucosidase Inhibitor, to Increase Active Glucagon-like Peptide-1 Levels Yusuke

More information

Metabolic Syndrome: What s so big about BIG?

Metabolic Syndrome: What s so big about BIG? Tuesday, 10:00 11:30, A2 Objectives: Notes: Metabolic Syndrome: What s so big about BIG? Patrice Conrad pbconrad1@att.net 1. Identify advances in clinical assessment and management of selected healthcare

More information

Clinical Overview of Combination Therapy with Sitagliptin and Metformin

Clinical Overview of Combination Therapy with Sitagliptin and Metformin Clinical Overview of Combination Therapy with Sitagliptin and Metformin 1 Contents Pathophysiology of type 2 diabetes and mechanism of action of sitagliptin Clinical data overview of sitagliptin: Monotherapy

More information

2.3 Carbon Compounds 12/19/2011 BIOLOGY MRS. MICHAELSEN. Lesson Overview. Carbon Compounds The Chemistry of Carbon. Lesson Overview.

2.3 Carbon Compounds 12/19/2011 BIOLOGY MRS. MICHAELSEN. Lesson Overview. Carbon Compounds The Chemistry of Carbon. Lesson Overview. 2.3 The Chemistry of Carbon A. Carbon atoms have four valence electrons 1. Form strong covalent bonds with many other elements: H, O, P, S, N. 2. Living organisms are made up of carbon and these other

More information

GLP-1 (glucagon-like peptide-1) Agonists (Byetta, Bydureon, Tanzeum, Trulicity, Victoza ) Step Therapy and Quantity Limit Criteria Program Summary

GLP-1 (glucagon-like peptide-1) Agonists (Byetta, Bydureon, Tanzeum, Trulicity, Victoza ) Step Therapy and Quantity Limit Criteria Program Summary OBJECTIVE The intent of the GLP-1 (glucagon-like peptide-1) s (Byetta/exenatide, Bydureon/ exenatide extended-release, Tanzeum/albiglutide, Trulicity/dulaglutide, and Victoza/liraglutide) Step Therapy

More information

Diabetes Oral Agents Pharmacology. University of Hawai i Hilo Pre-Nursing Program NURS 203 General Pharmacology Danita Narciso Pharm D

Diabetes Oral Agents Pharmacology. University of Hawai i Hilo Pre-Nursing Program NURS 203 General Pharmacology Danita Narciso Pharm D Diabetes Oral Agents Pharmacology University of Hawai i Hilo Pre-Nursing Program NURS 203 General Pharmacology Danita Narciso Pharm D 1 Learning Objectives Understand the role of the utilization of free

More information

Nutrition and Medicine, 2006 Tufts University School of Medicine Nutrition and Type 2 Diabetes: Learning Objectives

Nutrition and Medicine, 2006 Tufts University School of Medicine Nutrition and Type 2 Diabetes: Learning Objectives Nutrition and Medicine, 2006 Tufts University School of Medicine Nutrition and Type 2 Diabetes: Learning Objectives Margo N. Woods, D.Sc. 1. Discuss the increase in the incidence and prevalence of type

More information

SURGICAL CURES FOR DIABETES

SURGICAL CURES FOR DIABETES SURGICAL CURES FOR DIABETES UCSF Diabetes Update March 12, 2009 Andrew M. Posselt, MD, PhD Transplant Surgery, UCSF Surgical Treatment Options Whole Organ Pancreas Transplant Type 1 and 2 Pancreatic Islet

More information

The role of Hepatitis C Virus in hepatocarcinogenesis

The role of Hepatitis C Virus in hepatocarcinogenesis The role of Hepatitis C Virus in hepatocarcinogenesis Laura Beretta Fred Hutchinson Cancer Research Center l8 Incidence and mortality of the five most common cancers worldwide, 2000 Incidence Lung Breast

More information

Chapter 24 Diabetes Mellitus

Chapter 24 Diabetes Mellitus Chapter 24 Diabetes Mellitus Classification of Diabetes Mellitus Acute Effects of Diabetes Mellitus Chronic Complications of Diabetes Mellitus: Early Stages Chronic Complications of Diabetes Mellitus:

More information

Immunology/ Transplantation. Epidemiology/ Genetics. Mini-Symposium The Future Face of Diabetes Care Beta- Cell Replacement vs. Technology Room: 24

Immunology/ Transplantation. Epidemiology/ Genetics. Mini-Symposium The Future Face of Diabetes Care Beta- Cell Replacement vs. Technology Room: 24 FRIDAY, JUNE 9 Registration Hours: 9:00 a.m.-6:30 p.m. Shop Store Hours: 9:00 a.m.-6:30 p.m. Clinical / 11:30 a.m.- 12:30 p.m. Mini- Clinical Innovation in Vision Mini- Exercise for Type 1 The Stigma of

More information

DM, NAFLD, and conjugated linoleic acid (omega 6); what is the link

DM, NAFLD, and conjugated linoleic acid (omega 6); what is the link DM, NAFLD, and conjugated linoleic acid (omega 6); what is the link Mona Hegazy Professor of Internal Medicine Hepatology Department Cairo University Egypt Agenda Congugated lionleic fatty acid NAFLD

More information

Copy into Note Packet and Return to Teacher Section 3 Chemistry of Cells

Copy into Note Packet and Return to Teacher Section 3 Chemistry of Cells Copy into Note Packet and Return to Teacher Section 3 Chemistry of Cells Objectives Summarize the characteristics of organic compounds. Compare the structures and function of different types of biomolecules.

More information

The Metabolic Syndrome Update The Metabolic Syndrome: Overview. Global Cardiometabolic Risk

The Metabolic Syndrome Update The Metabolic Syndrome: Overview. Global Cardiometabolic Risk Update 2013 Marc Cornier, M.D. Associate Professor of Medicine Division of Endocrinology, Metabolism & Diabetes Anschutz Health and Wellness Center University of Colorado School of Medicine Denver Health

More information

Current evidence on the effect of DPP-4 inhibitor drugs on mortality in type 2 diabetic (T2D) patients: A meta-analysis

Current evidence on the effect of DPP-4 inhibitor drugs on mortality in type 2 diabetic (T2D) patients: A meta-analysis Current evidence on the effect of DPP-4 inhibitor drugs on mortality in type 2 diabetic (T2D) patients: A meta-analysis Raja Chakraverty Assistant Professor in Pharmacology Bengal College of Pharmaceutical

More information

Gene therapy: State of the art. Ramon Gomis MD, PhD, MAE. Hospital Clínic. IDIBAPS. University of Barcelona.

Gene therapy: State of the art. Ramon Gomis MD, PhD, MAE. Hospital Clínic. IDIBAPS. University of Barcelona. Gene therapy: State of the art Ramon Gomis MD, PhD, MAE. Hospital Clínic. IDIBAPS. University of Barcelona. Gene Therapy: First Steps Type 1 diabetes: An islet disease Alpha cell Beta cell Pancreatic

More information

Newer and Expensive treatment of diabetes. Endocrinology Visiting Associate Professor Institute of Medicine TUTH

Newer and Expensive treatment of diabetes. Endocrinology Visiting Associate Professor Institute of Medicine TUTH Newer and Expensive treatment of diabetes Jyoti Bhattarai MD Endocrinology Visiting Associate Professor Institute of Medicine TUTH Four out of every five people with diabetes now live in developing countries.

More information

Hormones. Prof. Dr. Volker Haucke Institut für Chemie-Biochemie Takustrasse 6

Hormones. Prof. Dr. Volker Haucke Institut für Chemie-Biochemie Takustrasse 6 Hormones Prof. Dr. Volker Haucke Institut für Chemie-Biochemie Takustrasse 6 Tel. 030-8385-6920 (Sekret.) 030-8385-6922 (direkt) e-mail: vhaucke@chemie.fu-berlin.de http://userpage.chemie.fu-berlin.de/biochemie/aghaucke/teaching.html

More information

Incretins: Their physiology and application in the treatment of diabetes mellitus

Incretins: Their physiology and application in the treatment of diabetes mellitus DIABETES/METABOLISM RESEARCH AND REVIEWS Diabetes Metab Res Rev 2014; 30: 354 371. Published online in Wiley Online Library (wileyonlinelibrary.com).2501 REVIEW ARTICLE Incretins: Their physiology and

More information

Secondary Negative Effects of Isolation Enzyme (s) On Human Islets. A.N.Balamurugan

Secondary Negative Effects of Isolation Enzyme (s) On Human Islets. A.N.Balamurugan Secondary Negative Effects of Isolation Enzyme (s) On Human Islets A.N.Balamurugan Human Islets Functional Mass Preservation 18-25 min 10 min 8-12 min 10-15 min 45-60 min pancreas in chamber 37º Sub-Optimal

More information

What s New in Diabetes Medications. Jena Torpin, PharmD

What s New in Diabetes Medications. Jena Torpin, PharmD What s New in Diabetes Medications Jena Torpin, PharmD 1 Objectives Discuss new medications in the management of diabetes Understand the mechanism of the medications discussed Understand the side effects

More information

Obesity and the Metabolic Syndrome in Developing Countries: Focus on South Asians

Obesity and the Metabolic Syndrome in Developing Countries: Focus on South Asians Obesity and the Metabolic Syndrome in Developing Countries: Focus on South Asians Anoop Misra Developing countries, particularly South Asian countries, are witnessing a rapid increase in type 2 diabetes

More information

Biomarkers of Pancreatic -cell Mass, Function, and Diabetes Treatment Selection

Biomarkers of Pancreatic -cell Mass, Function, and Diabetes Treatment Selection Biomarkers of Pancreatic -cell Mass, Function, and Diabetes Treatment Selection Creative Partnerships in Biopharmaceutical Research CQDM / Montreal in vivo Meeting 8 June, 2009 1 THE TEAM Marc Prentki

More information

Diabetes mellitus. Treatment

Diabetes mellitus. Treatment Diabetes mellitus Treatment Recommended glycemic targets for the clinical management of diabetes(ada) Fasting glycemia: 80-110 mg/dl Postprandial : 100-145 mg/dl HbA1c: < 6,5 % Total cholesterol: < 200

More information

Islets of Langerhans consist mostly of insulin-producing β cells. They will appear to be densely labeled

Islets of Langerhans consist mostly of insulin-producing β cells. They will appear to be densely labeled Are adult pancreatic beta cells formed by self-duplication or stem cell differentiation? Introduction Researchers have long been interested in how tissues produce and maintain the correct number of cells

More information

Pancreatic Cancer 2012 Report. Keeping the science current. programmes. cancer research and education. World Cancer Research Fund s

Pancreatic Cancer 2012 Report. Keeping the science current. programmes. cancer research and education. World Cancer Research Fund s World Cancer Research Fund American Institute for Cancer Research Continuous Update Project Keeping the science current Join a sponsored walk in your community to raise funds for World Cancer Research

More information

Thursday, September 5. Why are carbohydrates important for us to consume?

Thursday, September 5. Why are carbohydrates important for us to consume? Bell Work: Thursday, September 5 Carbon Video Why are carbohydrates important for us to consume? 1 O 2 CARBON What is it...and WY is it important? Carbon the building block of life, basis for most molecules

More information

Objectives. Insulin Resistance. Understanding the Basic Pharmacology of Medications for Type 2 Diabetes

Objectives. Insulin Resistance. Understanding the Basic Pharmacology of Medications for Type 2 Diabetes Understanding the Basic Pharmacology of Medications for Type 2 Diabetes Alan P. Agins, Ph.D. President, PRN Associates, Ltd Continuing Medical Education Tucson, AZ Objectives Describe the pathogenesis

More information

Hot Topics: The Future of Diabetes Management Cutting Edge Medication and Technology-Based Care

Hot Topics: The Future of Diabetes Management Cutting Edge Medication and Technology-Based Care Hot Topics: The Future of Diabetes Management Cutting Edge Medication and Technology-Based Care Mary Jean Christian, MA, MBA, RD, CDE Diabetes Program Coordinator UC Irvine Health Hot Topics: Diabetes

More information

Diabetes Mellitus in Older Adults. Presenter Disclosure Information

Diabetes Mellitus in Older Adults. Presenter Disclosure Information Diabetes Mellitus in Older Adults Medha Munshi, M.D. Joslin Diabetes Center Beth Israel Deaconess Medical Center Harvard Medical School Presenter Disclosure Information Medha Munshi Research grant from

More information

The most concentrated source of food energy. There are 9 calories in every gram of fat

The most concentrated source of food energy. There are 9 calories in every gram of fat Fat Is The most concentrated source of food energy There are 9 calories in every gram of fat Fats that are liquid at room temperature are called oils. (Examples: vegetable oil, canola oil, olive oil, etc.)

More information

Diabetes Medications: Oral Anti-Hyperglycemic Medications

Diabetes Medications: Oral Anti-Hyperglycemic Medications Diabetes Medications: Oral Anti-Hyperglycemic Medications Medication Types 1. Biguanides 2. Sulfonylureas 3. Thiazolidinediones (TZDs) 4. Alpha-Glucosidase Inhibitors 5. D-Phenylalanine Meglitinides 6.

More information

MLR-1023: A First-in-Class, Clinical Stage Candidate for Type II diabetes

MLR-1023: A First-in-Class, Clinical Stage Candidate for Type II diabetes MLR-1023: A First-in-Class, Clinical Stage Candidate for Type II diabetes» Next generation insulin sensitizer that does not have PPAR activity» Orally bioavailable small molecule» Weight neutral» β-cell

More information

ZL ZDF ZDF + E2 *** Visceral (g) ZDF

ZL ZDF ZDF + E2 *** Visceral (g) ZDF Body Weight (g) 4 3 2 1 ** * ZL ZDF 6 8 1 12 14 16 Age (weeks) B * Sub-cutaneous (g) 16 12 8 4 ZL ZDF Visceral (g) 25 2 15 1 5 ZL ZDF Total fat pad weight (g) 4 3 2 1 ZDF ZL Supplemental Figure 1: Effect

More information

Lesson Two Nutrients and the Body

Lesson Two Nutrients and the Body Lesson Two Nutrients and the Body Objectives After participating in this lesson, students will Be able to identify key nutrients the body needs and describe their function and importance. Understand that

More information

! acts via the autonomic nervous system. ! maintaining body weight within tight limits. ! ventromedial (VMN) ! arcuate (ARC) ! neuropeptide Y (NPY)

! acts via the autonomic nervous system. ! maintaining body weight within tight limits. ! ventromedial (VMN) ! arcuate (ARC) ! neuropeptide Y (NPY) Brain Regulates energy homeostatis Glucose Sensing in the Brain Seminar 2012 Gareth Price! acts in response to circulating signals of nutrient states! acts via the autonomic nervous system Ensures a balance

More information

1.1.1 Protein. 1 Quiz: Protein. 1. The main reason why the body needs protein is for growth, repair and maintenance.

1.1.1 Protein. 1 Quiz: Protein. 1. The main reason why the body needs protein is for growth, repair and maintenance. 1 Quiz: Protein 1.1.1 Protein 1. The main reason why the body needs protein is for growth, repair and maintenance. 2. An example of a protein alternative is mycoprotein, e.g. Quorn. 3. An example of a

More information

METABOLISMO E VITAMINA D

METABOLISMO E VITAMINA D CONVEGNO NAZIONALE GIBIS ROMA 14-15 MAGGIO 2015 METABOLISMO E VITAMINA D Alfredo Scillitani UO Endocrinologia Ospedale Casa Sollievo della Sofferenza Holick MF, NEJM 2007 Sindrome Metabolica E un cluster

More information

CNS Control of Food Intake. Adena Zadourian & Andrea Shelton

CNS Control of Food Intake. Adena Zadourian & Andrea Shelton CNS Control of Food Intake Adena Zadourian & Andrea Shelton Controlling Food Intake Energy Homeostasis (Change in body adiposity + compensatory changes in food intake) Background Information/Review Insulin

More information

Biological Molecules Ch 2: Chemistry Comes to Life

Biological Molecules Ch 2: Chemistry Comes to Life Outline Biological Molecules Ch 2: Chemistry Comes to Life Biol 105 Lecture 3 Reading Chapter 2 (pages 31 39) Biological Molecules Carbohydrates Lipids Amino acids and Proteins Nucleotides and Nucleic

More information

Dr. Hany M. Abo-Haded

Dr. Hany M. Abo-Haded BY Dr. Hany M. Abo-Haded Pediatric Cardiology Unit, Mansoura Universty Children Hospital, Mansoura, Egypt Co-authors: Dina S El-Agamy and Mohamed A Elkablawy Background Doxorubicin (DOX) is an anthracycline

More information

Effective Health Care Program

Effective Health Care Program Comparative Effectiveness Review Number 173 Effective Health Care Program Diabetes Medications for Adults With Type 2 Diabetes: An Update Executive Summary Condition and Therapeutic Strategies Type 2 diabetes

More information

Molecules of Life. Carbohydrates Lipids Proteins Nucleic Acids

Molecules of Life. Carbohydrates Lipids Proteins Nucleic Acids Molecules of Life Carbohydrates Lipids Proteins Nucleic Acids Molecules of Life All living things are composed of the following basic elements: Carbon Hydrogen Oxygen Nitrogen Phosphorous Sulfur Remember

More information

FARXIGA (dapagliflozin) Jardiance (empagliflozin) tablets. Synjardy (empagliflozin and metformin hydrochloride) tablets. GLUCOPHAGE* (metformin)

FARXIGA (dapagliflozin) Jardiance (empagliflozin) tablets. Synjardy (empagliflozin and metformin hydrochloride) tablets. GLUCOPHAGE* (metformin) Type 2 Medications Drug Class How It Works Brand and Generic Names Manufacturers Usual Starting Dose The kidneys filter sugar and either absorb it back into your body for energy or remove it through your

More information

Obesity Facts National Diabetes Fact Sheet. Pediatrics Grand Rounds 15 February 2013

Obesity Facts National Diabetes Fact Sheet. Pediatrics Grand Rounds 15 February 2013 2011 Obesity Prevalence Among Low Income Children Aged 2 to 4 Years New horizons for Therapy in Type 2 Diabetes Ana María Páez, MD Pediatric Endocrinology Obesity Facts During the past 20 years, there

More information

Nutrition Counselling

Nutrition Counselling Nutrition Counselling Frieda Dähler Augustiny, Nutritional Counsellor Preventive Cardiology & Sports Medicine University Clinic of Cardiology Optimal Diet for Prevention of Coronary Heart Disease Diet

More information

Biochemistry. Definition-

Biochemistry. Definition- Biochemistry Notes Biochemistry Definition- the scientific study of the chemical composition of living matter AND of the chemical processes that go on in living organisms. Biochemistry Facts 1. The human

More information

Autoimmunity. Autoimmunity arises because of defects in central or peripheral tolerance of lymphocytes to selfantigens

Autoimmunity. Autoimmunity arises because of defects in central or peripheral tolerance of lymphocytes to selfantigens Autoimmunity Autoimmunity arises because of defects in central or peripheral tolerance of lymphocytes to selfantigens Autoimmune disease can be caused to primary defects in B cells, T cells and possibly

More information

Biochemistry Notes MACROMOLECULES. Organic Compounds and Their Properties

Biochemistry Notes MACROMOLECULES. Organic Compounds and Their Properties Biochemistry Notes MACROMOLECULES Organic Compounds and Their Properties Organic Chemistry Organic chemistry is the study of: molecules containing carbon to carbon bonds. Macromolecules are very large

More information

Obesity and diabetes threaten European quality of life and regional health and social care budgets

Obesity and diabetes threaten European quality of life and regional health and social care budgets Obesity and diabetes threaten European quality of life and regional health and social care budgets Professor Mike Lean 3rd May 2017 Type 2 Diabetes in the 21 st Century A New Treatment Paradigm Professor

More information

α-cell role in β-cell generation and regeneration

α-cell role in β-cell generation and regeneration Islets ISSN: 1938-2014 (Print) 1938-2022 (Online) Journal homepage: http://www.tandfonline.com/loi/kisl20 α-cell role in β-cell generation and regeneration Joel F. Habener & Violeta Stanojevic To cite

More information

Diabetes Mellitus II CPG

Diabetes Mellitus II CPG 1 Diabetes Mellitus II CPG Candidates for Screening Integrated Complex Care Patients: Check Yearly Prediabetes: Check Yearly No Diabetes Mellitus (DM) Risk Factors: Check at Age 45, Repeat Every 3 Years

More information

Get off the SoFAS! Solid Fats and Added Sugars

Get off the SoFAS! Solid Fats and Added Sugars Get off the SoFAS! Solid Fats and Added Sugars Sponsored by: USDA through the Supplemental Nutrition Assistance Program, the School District of Philadelphia and the Department of NutritionSciences, Drexel

More information

A M Metabolics. inventing the future of healthcare

A M Metabolics. inventing the future of healthcare A M Metabolics inventing the future of healthcare Metabolic Disease Control Flavonoid-Based Amelioration of Carbohydrate Dysfunctional Metabolism December 2013 Daryl L. Thompson and M. Joseph Ahrens 2002

More information

1.3.1 Function of Food. Why do we need food?

1.3.1 Function of Food. Why do we need food? 1.3.1 Function of Food Why do we need food? Need to know The Function of Food Three reasons for requiring food 2 Food is needed for: 1.Energy 2.Growth of new cells and Repair of existing cells, tissues,

More information

Div. of Endocrinology and Metabolism Konyang University, School of Medicine. Byung-Joon Kim M.D., Ph.D.

Div. of Endocrinology and Metabolism Konyang University, School of Medicine. Byung-Joon Kim M.D., Ph.D. Diabetes and Thyroid Center Div. of Endocrinology and Metabolism Konyang University, School of Medicine Byung-Joon Kim M.D., Ph.D. Background Incretin effect and GLP 1 Receptor in L cells TGR5 receptor

More information

MULTIPLE CHOICE. Choose the one alternative that best completes the statement or answers the question.

MULTIPLE CHOICE. Choose the one alternative that best completes the statement or answers the question. Exam Name MULTIPLE CHOICE. Choose the one alternative that best completes the statement or answers the question. 1) Which of the following is TRUE about essential fatty acids? 1) A) No vegetables contain

More information

STEIN IN-TERM EXAM -- BIOLOGY APRIL 19, PAGE

STEIN IN-TERM EXAM -- BIOLOGY APRIL 19, PAGE STEIN IN-TERM EXAM -- BIOLOGY 3058 -- APRIL 19, 2018 -- PAGE 1 of 9 There are 25 questions in this Biology 3058 exam. All questions are "A, B, C, D, E, F, G, H" questions worth one point each. There is

More information

Research Article DevelopmentofaNongeneticMouseModelofType2Diabetes

Research Article DevelopmentofaNongeneticMouseModelofType2Diabetes Experimental Diabetes Research Volume, Article ID 65, pages doi:.55//65 Research Article DevelopmentofaNongeneticMouseModelofTypeDiabetes Elizabeth R. Gilbert, Zhuo Fu, and Dongmin Liu Department of Human

More information

Insights into insulin resistance and type 2 diabetes from knockout mouse models

Insights into insulin resistance and type 2 diabetes from knockout mouse models Insights into insulin resistance and type 2 diabetes from knockout mouse models Takashi Kadowaki Department of Metabolic Diseases, Graduate School of Medicine, University of Tokyo, Tokyo 113-8655, Japan.

More information

Learning Objectives. Impact of Diabetes II UPDATES IN TYPE 2 DIABETES. David Doriguzzi, PA-C

Learning Objectives. Impact of Diabetes II UPDATES IN TYPE 2 DIABETES. David Doriguzzi, PA-C UPDATES IN TYPE 2 DIABETES David Doriguzzi, PA-C Learning Objectives Upon completion of this educational activity, the participant should be able to: Overcome barriers and attitudes that limit Clinician/Patient

More information

This program applies to Commercial, GenPlus and Health Insurance Marketplace formularies.

This program applies to Commercial, GenPlus and Health Insurance Marketplace formularies. OBJECTIVE The intent of the GLP-1 (glucagon-like peptide-1) Agonists [Adlyxin (lixisenatide), Byetta (exenatide), Bydureon (exenatide extended-release), Tanzeum (albiglutide), Trulicity (dulaglutide),

More information

8/21/2017 UNRAVELING THE CROWED INSULIN SCENE. A Practical Overview of Insulin Focusing on New Insulin Preparations

8/21/2017 UNRAVELING THE CROWED INSULIN SCENE. A Practical Overview of Insulin Focusing on New Insulin Preparations UNRAVELING THE CROWED INSULIN SCENE A Practical Overview of Insulin Focusing on New Insulin Preparations Patricia Garnica MS, ANP-BC, CDE, CDTC North Shore University Hospital, Manhasset, N.Y. October

More information

Cover Page. The handle holds various files of this Leiden University dissertation.

Cover Page. The handle  holds various files of this Leiden University dissertation. Cover Page The handle http://hdl.handle.net/1887/32608 holds various files of this Leiden University dissertation. Author: Ellenbroek, Johanne Hendrike (Rianne) Title: Pancreatic β- and α-cell adaptation

More information

STEIN IN-TERM EXAM -- BIOLOGY APRIL 21, PAGE

STEIN IN-TERM EXAM -- BIOLOGY APRIL 21, PAGE STEIN IN-TERM EXAM -- BIOLOGY 3058 -- APRIL 21, 2016 -- PAGE 1 of 9 There are 25 questions in this Biology 3058 exam. All questions are "A, B, C, D, E, F, G, H" questions worth one point each. There is

More information

Chapter 3- Organic Molecules

Chapter 3- Organic Molecules Chapter 3- Organic Molecules CHNOPS Six of the most abundant elements of life (make up 95% of the weight of all living things)! What are they used for? Structures, enzymes, energy, hormones, DNA How do

More information