Hormonal regulation of. Physiology Department Medical School, University of Sumatera Utara

Transcription

1 Hormonal regulation of nutrient metabolism Physiology Department Medical School, University of Sumatera Utara

2 Homeostasis & Controls Successful compensation Homeostasis reestablished Failure to compensate Pathophysiology Illness Death

3 Metabolic pathways of nutrients Food intake Dietary protein Dietary carbohydrate Dietary triglyceride fat D I G E S T I O N Absorbable units Amino acids Glucose Fatty acids Monoglycerides A B S O R P T I O N Metabolic pool in body Body proteins (structural or secretory products) Amino acids Urea Urinary excretion (elimination from body) Storage, structural, and functional macromolecules in cells Glycogen storage in liver and muscle Glucose Oxidation to CO 2 + H 2 O + ATP (energy) Expired (elimination from body) Triglycerides in adipose tissue stores (fat) Fatty acids Use as metabolic fuel in cells

4 Summary of Metabolic Conversions of Nutrients

5 Types of Changes in Target Cells plasma membrane permeability changes (opening of protein channels; may change membrane potential) activation of genes for increased protein synthesis, including enzymes activation or deactivation of enzymes already present secretion of cellular products stimulation of cell division (mitosis)

6 Regulation of Glucose Metabolism Under normal conditions, the body maintains a serum glucose concentration that ranges between 70 and 110 mg/dl Three main organic components of food: Carbohydrates Fats Proteins Process of digestion Carbohydrate metabolism Fat metabolism Protein metabolism

7 [Glucose] in blood: control by insulin and glucagon Mechanisms in response to high [glucose] blood Adequate [glucose] blood must be maintained mainly because the brain uses almost exclusively glucose as an energy source. But, high [glucose] can also be dangerous, partly because it leads to downregulation of insulin receptors and possible coma when [glucose] returns to normal, and partly because it leads to long-term tissue damage by abnormal protein glucosylation. Mechanisms in response to high [glucose] blood glucose entry into cells glucose metabolism to glycogen (liver & muscle) or fat (adipose tissue) Mechanisms in response to low [glucose] blood glycogenolysis gluconeogenesis (from pyruvate or lactate) In response to low glucose entry to cells (diabetes): production of fatty acids and ketoacids as alternate energy sources

8 The Endocrine Pancreas The gross anatomy of the pancreas A pancreatic islet surrounded by exocrinesecreting cells

9 Pancreatic Islets Alpha cells produce glucagon (a 51 amino acid peptide hormone) Betacellsproduceinsulin(a29amino acid peptide hormone) Islets heavily invested with capillaries Islets innervated by both sympathetic and parasympathetic neurons The Endocrine Pancreas

10 The Pancreas Secretes Insulin And Glucagon Theendocrinecellsofthepancreasare contained in the pancreatic islets or islets of Langerhans. Thesemakeuponly1-2%ofthemass of the pancreas. They are scattered throughout the pancreas. The Endocrine Pancreas

11 The Insulin-glucagon Ratio Regulates Metabolism Insulin and glucagon act in an antagonistic fashion to keep plasma glucose concentrations within an acceptable range( mg/dl). Botharepresentinthebloodmostof the time. The ratio of the two hormones determines which hormone dominates. The Endocrine Pancreas

12 Insulin (β cells of endocrine pancreas) Insulin Is The Dominant Hormone Of The Fed State Secretion of insulin is affected by the following factors: 1. Increased glucose concentrations 2. Increased amino acid concentrations 3. Feedforward effects of GI hormones 4. Parasympathetic activity 5. Sympathetic activity The Endocrine Pancreas

13 The Endocrine Pancreas

14 The Endocrine Pancreas

15 Insulin Promotes Anabolism Insulin lowers plasma glucose by: 1. Increasing glucose transport into most insulin sensitive cells 2. Enhancing cellular utilization and storage of glucose 3. Enhancing utilization of amino acids 4. Promoting fat synthesis The Endocrine Pancreas

16 Insulin promotes insertion of GLUT 4 in adipocytes and muscle cells The Endocrine Pancreas

17 Insulin promotes glucose uptake by stimulating hexokinase activity The Endocrine Pancreas

18 Factors influencing insulin secretion : blood glucose insulin secretion, glucagon amino acids in blood insulin secretion fatty acids insulin secretion, glucagon parasympathetic activity insulin secretion sympathetic activity insulin secretio glucagon secretion GIP(gastric-inhibiting peptide) insulin secretion glucagon-like peptide 1 (GLP-1) insulin secretion The Endocrine Pancreas

19 Regulation of insulin secretion Gastrointestinal hormones Blood glucose concentration Blood amino acid concentration Food intake Major control Parasympathetic stimulation Islet b cells Sympathetic stimulation (and epinephrine) Insulin secretion Blood glucose Blood fatty acids Blood amino acids Protein synthesis Fuel storage The Endocrine Pancreas

20 Glucagon (α cells of endocrine pancreas) Glucagon Is Dominant In The Fasted State Glucagon prevents hypoglycemia. Glucagon is secreted when plasma glucose levels fall below 100 mg/dl. The liver is the primary target of glucagon. Glucagon stimulates glycogenolysis and gluconeogenesis to increase glucose output by the liver. Glucagon release is also stimulated by plasma amino acids. The Endocrine Pancreas

21 Factors influencing glucagon secretion : Low blood glucose glucagon secretion, insulin High blood glucose glucagon glucagon secretion aa in blood glucagon secretion Sympathetic stimulation The Endocrine Pancreas

22 Functions: blood glucose glycogenesis and glycogenolysis gluconeogenesis in liver cells lipogenesis and lipolysis ketone production little effect on muscle protein The Endocrine Pancreas

23 Glucagon predominates in the fasted state The Endocrine Pancreas

24 The Endocrine Pancreas

25 The Endocrine Pancreas

26 The Endocrine Pancreas

27 Thyroid hormone Synthesized by thyroid gland from storage form thyroglobulin in the colloid within the follicles of the gland.

28 Thyroxine and its precursors: Structure & Synthesis Thyroid hormone

29 Thyroid hormone

30 Regulation of TH secretion Neuronal stimuli (stress, skin temp) -Secreted T 4 : T 3 (20:1) - T 3 is 5X more potent than T 4 T 4 converted to T 3 at the kidneys, liver and heart Thyroid hormone

31 Thyroid Gland: T 4 and T 3 affect metabolic rate of every cell in the body, except brain, spleen, testes, uterus and thyroid gland affect other activities within these organs and glands readily cross membranes (diffuse through plasma membrane to bind to mitochondrial receptors and receptors in nucleus) Thyroid hormone

32 Functions of TH TH is primary determinant of MR BMR (calorigenic effect) Thermogenic heart rate GH secretion Essential for development and normal functioning of the nervous system Concentration-dependent effects on protein, carbohydrates and fat metabolism Modulates the effects of other hormones by exerting a permissive action Thyroid hormone

33 Factors influencing TH secretion : Thyrotropin-releasing hormone (TRH) is tonically secreted Neuronal stimuli (e.g. stress or exposure to cold) stimulates release of TRH from the hypothalamus TRH stimulates release of thyroid-stimulating hormone (TSH) from the anterior pituitary TSH in turn stimulates the release of thyroid hormones (T 4 and T 3 ) THs exerts a negative feedback on their own production Thyroid hormone

34 Adrenal Gland: Regions and Zones Adrenal Gland

35 Adrenal Cortex: Zona Fasciculata glucocorticoids - effects on glucose metabolism main hormone is CORTISOL (hydrocortisone) actions: * Affects glucose, protein, fat metabolism. Inhibits synthesis of protein in tissues. Promotes the use of fatty acids as energy source and decreases the use of glucose. Stimulates liver cells to synthesize glucose from noncarbohydrates (gluconeogenesis) and increases blood glucose concentrations. * Anti-inflammatory decrease immune response * can be used clinically to treat allergic reactions (e.g., poison ivy), rheumatoid arthritis Adrenal Gland

36 Cortisol Regulation Adrenal Gland

37 Regulation Cortisol Adrenal Gland

38 Adrenal Medulla catecholamines - epinephrine (~80%), norepinephrine (NE) control: secretion stimulated by preganglionic fibers of sympathetic nerves during flight-or-fight response Adrenal Gland

39 Epinephrine (adrenal medulla) Functions: Reinforces sympathetic nervous system during stress and exercise Mobilization of stored carbohydrates and fat to provide energy for muscular work Increases blood glucose by hepatic gluconeogenesis and glycogenolysis in liver and muscle insulin secretion, glucagon and ACTH secretion lipolysis Adrenal Gland

40 Adrenal Medulla actions: epinephrine (more potent) - increases HR (beta receptors), bronchodilation (in lungs), increased blood glucose (breakdown of glycogen in liver and skeletal muscle, and breakdown of adipose tissue) NE - peripheral vasoconstriction --> increased BP Adrenal Gland

41 Stress Pathways Adrenal Gland

42 Tissues can be targeted by multiple hormones Hormones can act synergistically, permissively, or antagonistically Synergistic effects of hormones on blood glucose concentration

43 Growth hormone (somatotropin) Synthesized and secreted by the anterior pituitary Secretion under circadian control Stimulates insulin-like growth factors (IGFs) from liver and other tissues Secreted in adults and has metabolic effects unrelated to growth Growth hormone

44 Functions of GH Stimulates IGF secretion protein synthesis and growth uptake of amino acids by liver and muscle lipolysis in adipose tissue fatty acids in blood glucose uptake by muscle blood glucose Growth hormone

45 Factors influencing GH secretion : amino acids in blood GH secretion fatty acids in blood GH secretion blood glucose GH secretion Deep sleep, exercise, stress and hypoglycemia influence GH secretion Growth hormone-releasing hormone (GHRH) stimulates GH secretion Somatostatin inhibits GH secretion Growth hormone

46 Growth hormone pathway Growth hormone

47 Testosterone Steroid Hormone Major function : Reproductive function on sprematogenesis and secondary sex organ development Other reproductive related effect Development of sexual libido of puberty and help maintain the sex drive in the adult male Non reproductive action

48 Testosterone It has a protein anabolic (synthesis) effect Promote bone growth Prevent further growth by sealing the growing ends of the long bone (closing the epiphyseal plate) Contribute to the more muscular physique of male and to pubertal growth spurt