From 1552 BC to 2015:

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From 1552 BC to 2015: How Science Made Diabetes Treatable Mary Gearing Biological and Biomedical Sciences Program, Harvard University

Outline 1. A (Very!) Short History of Diabetes 2. Diabetes Research and Treatment Today

Diabetes: one of the oldest diseases known to man. First documented in 1552 BC Egyptian physician: Hesy-Ra Symptoms: Rapid weight loss Frequent urination Urine attracted ants Hesy-Ra (public domain)

1st century CE: Arateus A melting down of flesh into urine Coined the term diabetes mellitus Diabetes: siphon, passing through Mellitus: sweet (sugar) Diabetes is a death sentence through the early 20 th century! Scientific lesson: Must understand the disease biology, not just the symptoms! Effects of insulin therapy from Geyelin 1922 (public domain)

1889: Finding a cause for diabetes Minkowski/von Mering Removed pancreas from dogs Rapid onset of diabetes Scientific lesson: Key discoveries are often unexpected! CC BY 3.0 Blausen.com staff. "Blausen gallery 2014". Wikiversity Journal of Medicine. ISSN 20018762 - Own work

1869: Looking closely at the pancreas Paul Langerhans two types of pancreatic structures Islets (??) (Digestion) Are the islets important in diabetes? Diabetes = loss of an islet protein (insulin) Can we isolate insulin and use it to treat patients? CC BY 3.0 Illustration from Anatomy & Physiology, Connexions Website by Openstax College. http://cnx.org/content/col11496/1.6/ Jun 19, 2013.

1921: Banting/Best and Macleod Treated diabetic dogs with pancreatic extract Some success but lots of technical problems Scientific lesson: If at first you don t succeed, try and try again. C. H. Best and F. G. Banting ca. 1924 (public domain)

Banting/Best and Macleod/Collip 1922: Treated diabetic children Scientific lesson: When you find something big, run with it! Nobel Peace Prize (public domain); Effects of insulin therapy from Geyelin 1922 (public domain)

What does insulin do? Insulin (hormone) food signal Energy uptake and storage Breakdown of stored energy (fat, proteins) Good Food Display - NCI Visuals Online (public domain)

Insulin and glucose (sugar) bloodstream inside of the cell Effect of insulin on glucose uptake and metabolism (public domain)

Type 1 vs Type 2 diabetes Type I diabetes (10%, <30 at diagnosis) Type 2 diabetes (90%, assoc. with obesity) Effect of insulin on glucose uptake and metabolism (public domain), Day 94: Earplugs by Quinn Dombrowski (CC BY-SA 2.0)

Recap Insulin is a hormone that controls glucose metabolism. Type 1 diabetes: insulin is absent Type 2 diabetes: the body doesn t respond properly to insulin Questions??

Outline 1. A (Very!) Short History of Diabetes 2. Diabetes Research and Treatment Today

Current diabetes treatments Insulin pumps Synthetic insulin produced by engineered bacteria or yeast Glucoselowering drugs Animas Vibe - insulin pump and CGM system by Alden Chadwick (CC BY 2.0); Generic metformin (public domain) ; Insulin vial (public domain)

What problems remain Today: diabetic life expectancy is 10-13 years lower than for non-diabetics. A cure has remained elusive. does not equal Animas Vibe - insulin pump and CGM system by Alden Chadwick (CC BY 2.0); Blausen.com staff. "Blausen gallery 2014". Wikiversity Journal of Medicine. ISSN 20018762 - Own work (CC BY 3.0)

Insulin is very complicated! Insulin Insulin bloodstream receptor GLUT-4 Glucose inside of the cell Insulin action on the cell process (Figure 1.1.2) by The firesofedition (CC BY-SA 3.0)

Complications: blood vessels Microvascular (small vessels) Macrovascular (large vessels) Kidney disease Nerve death Eye disease Atherosclerosis Heart attack Stroke Pain/suffering Death (>65%)

New research in type I diabetes Stem cells! Stem cells Artificial pancreas Insulin-producing cells Transplantation into diabetic mouse Drawing of a grey mouse by Jan Gilbank (CC BY 3.0); Stem cell figure adapted from Pagliuca et al., 2014

Conclusions Diabetes: a research success story One door opens another Research today aimed at: Decreasing diabetic complications Stem cell therapies (type I) Preventing type 2 diabetes and prediabetes (~30% of population)

What can you do? Lead a healthy lifestyle (diet and exercise) Support biomedical research Foods from plant sources (public domain); World Diabetes Day (public domain)

Thank you! SITN would like to acknowledge the following organizations for their generous support of this event.