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Transcript
The Endocrine Pancreas Regulation of Carbohydrate Metabolism Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Nutritional Requirements Living tissue is maintained by constant expenditure of energy (ATP). Energy of food is commonly measured in kilocalories. Indirectly from glucose, fatty acids, ketones, amino acids, and other organic molecules. One kilocalorie is = 1000 calories. One calorie = amount of heat required to raise the temperature of 1 cm3 of H20 from 14.5o to 15.5o C. The amount of energy released as heat when food is combusted in vitro = amount of energy released within cells through aerobic respiration. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Metabolic Rate and Caloric Requirements Metabolic rate is the total rate of body metabolism. BMR: Metabolic rate measured by the amount of oxygen consumed by the body/min. Oxygen consumption of an awake relaxed person 12–14 hours after eating and at a comfortable temperature. BMR determined by: Age. Gender. Body surface area. Thyroid secretion. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Anabolic Requirements Anabolism: Synthesize: Food supplies raw materials for synthesis reactions. DNA and RNA. Proteins. Triglycerides. Glycogen. Must occur constantly to replace molecules that are hydrolyzed. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Aerobic Requirements (continued) Catabolism: Hydrolysis (break down monomers down to CO2 and H2O.): Hydrolysis reactions and cellular respiration. Gluconeogenesis. Glycogenolysis. Lipolysis. How do we use food components in catabolic and anabolic pathways? Involves specific chemical reactions: - Each reaction is catalyzed by a specific enzyme. - Other compounds, besides those being directly metabolized, are required as intermediates or catalysts in metabolic reactions - adenosine triphosphate (ATP) - nicotinamide adenine dinucleotide (NAD+) - flavin adenine dinucleotide (FAD+) - Coenzyme A ATP ATP is the energy currency of the cell The structure of ATP is similar to that of nucleic acids The energy in ATP is “carried” in the phosphate groups - to convert ADP into ATP requires energy - the energy is stored as potential energy in the phosphate group bond - removal of the third phosphate releases that energy NADH, FADH2 NAD+ can accept a hydrogen ion and become reduced to NADH: NAD+ + 2[H+] + 2e- NADH + H+ The added hydrogen ion (and electrons) can be carried to and used in other reactions in the body. FAD+ is similarly reduced to FADH2. NADH and FADH carry hydrogen ions and electrons to the enzymes in the electron transport chain of the mitochondria, allowing ATP production there. Coenzyme A The enzyme coenzyme A converts acetyl groups (2-carbon structures) into acetyl CoA, which can then be used in metabolic reactions During the course of acetyl CoA production, energy is released and is used to convert NAD+ to NADH Cellular Respiration Generating ATP from food requires glycolysis, the Krebs Cycle, and the electron transport chain. Overall reaction: C6H12O6 + 6 O2----> 6 CO2 + 6 H2O + 38 ATP + heat The Main point: the break down of glucose releases LOTS of energy: - about 40% in usable form (ATP) - about 60% as heat Glycolysis Glycolysis is the breakdown of glucose into pyruvic acid Two main steps are involved, occurring in the cytoplasm of cells (no organelles involved). The two main steps of glycolysis: Step one: glucose glucose 6-phosphate ATP ATP fructose 1,6diphosphate Step two: fructose 1,6diphosphate 2 pyruvic acid 2 NADH 2 ATP 2 ATP What happens to pyruvic acid? In aerobic respiration (oxygen present): - pyruvic acid moves from cytoplasm to mitochondria - pyruvic acid (3 carbons) is converted to acetyl group (2 carbons), producing CO2 in the process - acetyl group is converted to acetyl CoA by coenzyme A - acetyl CoA is used in the Krebs cycle. Krebs Cycle Acetyl CoA combines with oxaloacetic acid, forming citric acid A series of reactions then occurs resulting in: - one ATP produced - three NADH and one FADH2 produced (go to electron transport chain) - two CO2 molecules produced Electron-transport Chain The main point: NADH and FADH2 carry H+ ions to the electron-transport chain, resulting in production of ATP To do this, the H+ ions are moved along the transport chain, eventually accumulating in the outer mitochondrial compartment The H+ ions move back into the inner mitochondrial compartment via hydrogen channels, which are coupled to ATP production. At the end of the transport chain, four hydrogen ions join with two oxygen molecules to form water: 4 H+ + O2 ----> 2 H2O In the absence of oxygen, the transport chain stalls (no ATP production) Net Result of Glycolysis, Citric Acid Cycle, and Electron Transport Chain: Production of ATP (stored, potential energy for chemical reactions in the body; 40% of energy released). Production of heat (maintains body temperature; 60% of energy released). Also, production of CO2 and H2O. Storage and Utilization of Glycogen Excess glucose can be stored as glycogen. glucose glucose glucose glycogen 6-phosphate 1-phosphate Stored glycogen can be utilized, by glycogenolysis. Glycogenolysis: -glycogen is broken down into glucose 6phosphate - liver transforms glucose 6-phosphate to glucose, maintaining blood glucose levels Lipid Metabolism Over 95% of stored energy in the body is in the form of triacylglycerol During lipid catabolism (lipolysis), triacylglycerol is broken down into free fatty acids and glycerol Free fatty acids are metabolized by betaoxidation: 1) fatty acid (18 C) + coenzyme A 2) fatty acid (18 C)-coA 3) fatty acid (16 C) and acetyl-coA Acetyl-CoA used in citric acid cycle This reaction also yields NADH => electron transport chain Excess acetyl-CoA forms ketone bodies Lipid Metabolism (cont.) The glycerol is converted into glyceraldehyde 3-phosphate, which is converted to pyruvic acid Pyruvic acid is metabolized under aerobic conditions into acetyl-coA While lipids are major storage form of energy, accessing lipids for metabolism takes time - water insoluble - less efficient energy source - potential for keto-acidosis Protein Metabolism Amino acids are NOT stored for energy However, protein can be broken down, and amino acids can be modified and utilized to create glucose or for metabolism Modification of amino acids to produce substrate for energy involves oxidative deamination Oxidative Deamination Oxidative deamination removes the amino group from the amino acid, forming ammonia, NADH, and a keto acid: NADH => electron transport chain ammonia => liver, converted to urea keto acid => acetyl-coA => citric acid cycle Proteins and Energy Utilization of proteins for quick energy is not very efficient: - more difficult to break apart (multiple proteases) - toxic byproduct (ammonia) - can get accumulation of keto acids - proteins are important structural and functional components of cells Interconversion of Nutrients Lipogenesis: once glycogen stores are filled, glucose and amino acids are converted to lipids Rate limiting enzyme: acetyl CoA carboxylase glucose glucose 6-phosphate glyceraldehyde glycerol 3-phosphate acetyl CoA carboxylase amino acids acetyl CoA fatty acids triglycerides Interconversion of Nutrients (cont.) Gluconeogenesis: amino acids and glycerol can be used to produce glucose (liver) More glucose is produced via gluconeogenesis than glycogenolysis Rate-limiting enzyme: phosphoenolpyruvate carboxykinase Glycerol glyceraldehyde 3- phosphate glucose 6-phosphate phosphoenol pyruvate PEPCK oxaloacetate Amino acids pyruvic acid glucose Importance of Blood Glucose Homeostasis Blood glucose levels must be maintained as a nutrient source for nervous tissue (no glucose stores) What mechanisms regulate blood nutrient levels in tissues and blood glucose levels? The Endocrine Pancreas: Regulation of Nutrient Metabolism Located on the posterior abdominal wall, retroperitoneal. Exocrine portion: secretes digestive enzymes via pancreatic duct, to small intestine. Endocrine portion: pancreatic islets (of Langerhans), involved in regulation of blood glucose levels. Production of Pancreatic Hormones by Three Cell Types Alpha cells produce glucagon. Beta cells produce insulin. Delta cells produce somatostatin. Structure of Insulin Insulin is a polypeptide hormone, composed of two chains (A and B) BOTH chains are derived from proinsulin, a prohormone. The two chains are joined by disulfide bonds. Roles of Insulin Acts on tissues (especially liver, skeletal muscle, adipose) to increase uptake of glucose and amino acids. - without insulin, most tissues do not take in glucose and amino acids well (except brain). Increases glycogen production (glucose storage) in the liver and muscle. Stimulates lipid synthesis from free fatty acids and triglycerides in adipose tissue. Also stimulates potassium uptake by cells (role in potassium homeostasis). The Insulin Receptor As we previously saw, the insulin receptor is composed of two subunits, and has intrinsic tyrosine kinase activity. Activation of the receptor results in a cascade of phosphorylation events: phosphorylation of insulin responsive substrates (IRS) RAS RAF-1 MAP-K MAP-KK Final actions Specific Targets of Insulin Action: Carbohydrates Increased activity of glucose transporters. Moves glucose into cells. Activation of glycogen synthetase. Converts glucose to glycogen. Inhibition of phosphoenolpyruvate carboxykinase. Inhibits gluconeogenesis. Specific Targets of Insulin Action: Lipids Activation of acetyl CoA carboxylase. Stimulates production of free fatty acids from acetyl CoA. Activation of lipoprotein lipase (increases breakdown of triacylglycerol in the circulation). Fatty acids are then taken up by adipocytes, and triacylglycerol is made and stored in the cell. lipoprotein lipase Regulation of Insulin Release Major stimulus: increased blood glucose levels - after a meal, blood glucose increases - in response to increased glucose, insulin is released - insulin causes uptake of glucose into tissues, so blood glucose levels decrease. - insulin levels decline as blood glucose declines FOOD Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Storage In Fat Depots Inhibition of Lipolysis I Insulin Secretion I Insulin Pancreas Restrain of HGO I Insulin Effects Uptake of glucose Effect of Glucose on Insulin Release Glucose enters beta cell through a glucose transporter. Glucose is utilized to generate ATP. ATP closes a potassium channel, depolarizing the beta cell membrane (normally, K+ leaks out of cell). Depolarization activates a voltage-dependent calcium channel, increasing intracellular calcium levels. Increased calcium triggers insulin release. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. The synthesis and release of insulin is modulated by: 1. Glucose (most important), AAs, FAs and ketone bodies stimulate release. 2. Glucagon and somatostation inhibit relases 3. α-Adrenergic stimulation inhibits release (most important). 4. β-Adrenergic stimulation promotes release. 5. Elevated intracellular Ca2+ promotes release. Insulin secretion - Insulin secretion in beta cells is triggered by rising blood glucose levels. Starting with the uptake of glucose by the GLUT2 transporter, the glycolytic phosphorylation of glucose causes a rise in the ATP:ADP ratio. This rise inactivates the potassium channel that depolarizes the membrane, causing the calcium channel to open up allowing calcium ions to flow inward. The ensuing rise in levels of calcium leads to the exocytotic release of insulin from their storage granule. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Mechanism of Insulin Action Insulin binds to specific high affinity membrane receptors with tyrosine kinase activity Phosphorylation cascade results in translocation of Glut4 (and some Glut-1) transport proteins into the plasma membrane. It induces the transcription of several genes resulting in increased glucose catabolism and inhibits the transcription of genes involved in gluconeogenesis. Insulin promotes the uptake of K+ into cells. Other Factors Regulating Insulin Release Amino acids stimulate insulin release (increased uptake into cells, increased protein synthesis). Keto acids stimulate insulin release (increased glucose uptake to prevent lipid and protein utilization). Insulin release is inhibited by stress-induced increase in adrenal epinephrine - epinephrine binds to alpha adrenergic receptors on beta cells - maintains blood glucose levels Glucagon stimulates insulin secretion (glucagon has opposite actions). Structure and Actions of Glucagon Peptide hormone, 29 amino acids Acts on the liver to cause breakdown of glycogen (glycogenolysis), releasing glucose into the bloodstream. Inhibits glycolysis Increases production of glucose from amino acids (gluconeogenesis). Also increases lipolysis, to free fatty acids for metabolism. Result: maintenance of blood glucose levels during fasting. Mechanism of Action of Glucagon Main target tissues: liver, muscle, and adipose tissue Binds to a Gs-coupled receptor, resulting in increased cyclic AMP and increased PKA activity. Also activates IP3 pathway (increasing Ca++) Targets of Glucagon Action Activates a phosphorylase, which cleaves off a glucose 1-phosphate molecule off of glycogen. Inactivates glycogen synthase by phosphorylation (less glycogen synthesis). Increases phosphoenolpyruvate carboxykinase, stimulating gluconeogenesis Activates lipases, breaking down triglycerides. Inhibits acetyl CoA carboxylase, decreasing free fatty acid formation from acetyl CoA Result: more production of glucose and substrates for metabolism Regulation of Glucagon Release Increased blood glucose levels inhibit glucagon release. Amino acids stimulate glucagon release (high protein, low carbohydrate meal). Stress: epinephrine acts on beta-adrenergic receptors on alpha cells, increasing glucagon release (increases availability of glucose for energy). Insulin inhibits glucagon secretion. Other Factors Regulating Glucose Homeostasis Glucocorticoids (cortisol): stimulate gluconeogenesis and lipolysis, and increase breakdown of proteins. Epinephrine/norepinephrine: stimulates glycogenolysis and lipolysis. Growth hormone: stimulates glycogenolysis and lipolysis. Note that these factors would complement the effects of glucagon, increasing blood glucose levels. Hormonal Regulation of Nutrients Right after a meal (resting): - blood glucose elevated - glucagon, cortisol, GH, epinephrine low - insulin increases (due to increased glucose) - Cells uptake glucose, amino acids. - Glucose converted to glycogen, amino acids into protein, lipids stored as triacylglycerol. - Blood glucose maintained at moderate levels. Hormonal Regulation of Nutrients A few hours after a meal (active): - blood glucose levels decrease - insulin secretion decreases - increased secretion of glucagon, cortisol, GH, epinephrine - glucose is released from glycogen stores (glycogenolysis) - increased lipolysis (beta oxidation) - glucose production from amino acids increases (oxidative deamination; gluconeogenesis) - decreased uptake of glucose by tissues - blood glucose levels maintained Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Turnover Rate Rate at which a molecule is broken down and resynthesized. Average daily turnover for carbohydrates is 250 g/day. Some glucose is reused to form glycogen. Only need about 150 g/day. Average daily turnover for protein is 150 g/day. Some protein may be reused for protein synthesis. Only need 35 g/day. 9 essential amino acids. Average daily turnover for fats is 100 g/day. Little is actually required in the diet. Fat can be produced from excess carbohydrates. Essential fatty acids: Linoleic and linolenic acids. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Regulation of Energy Metabolism Energy reserves: Molecules that can be oxidized for energy are derived from storage molecules (glycogen, protein, and fat). Circulating substrates: Molecules absorbed through small intestine and carried to the cell for use in cell respiration. Insert fig. 19.2 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Eating Eating behaviors partially controlled by hypothalamus. Lesions in vetromedial area produce hyperphagia (obesity). Lesions in lateral hypothalamus produces hypophagia (weight loss). Endorphins, NE, serotonin, and CCK affect hunger and satiety. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Regulatory Functions of Adipose Tissue Adipostat regulatory system (negative feedback loops) to defend amount of adipose tissue. Differentiation of adipocytes require nuclear receptor protein (PPARg) which is activated when bound to 15-D PGJ2: Number of adipocytes increase after birth. Stimulates adipogenesis by promoting development of preadipocytes into mature adipocytes. Differentiation promoted by high [fatty acids]. Adipocytes store fat within large vacuoles. May secrete hormones involved in regulation of metabolism. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Regulatory Functions of Adipose Tissue (continued) Leptin: Hormone that signals the hypothalamus to indicate the level of fat storage. Involved in long-term regulation of eating. Neuropeptide Y: Potent stimulator of appetite. Functions as a NT within the hypothalamus. Satiety factor in obese have decreased sensitivity to leptin in the brain. These neurons are inhibited by leptin. TNFa: Acts to reduce the sensitivity of cells to insulin. Increased in obesity. May contribute to insulin resistance. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Regulation of Hunger Adipose tissue secrete satiety factor: Acts through its regulation of hunger centers in hypothalamus. Ghrelin: Secreted by stomach. CCK: Secretions rise during and immediately after a meal. Secretions rise between meals and stimulate hunger. Produce satiety. PYY3-36: Acts within the hypothalamus. Decreases neuropeptide Y. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Obesity Obesity is often diagnosed by using using a body mass index (BMI). BMI = w h2 w = weight in kilograms h = height in meters Healthy weight as BMI between 19 – 25. Obesity defined as BMI > 30. Obesity in childhood is due to an increase in both the size and the # of adipocytes. Weight gains in adulthood is due to increase in adipocyte size in intra-abdominal fat. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Calorie Expenditures 3 components: Basal metabolic rate (BMR): Adaptive thermogenesis: 60% total calorie expenditure. 10% total calorie expenditure. Physical activity: Contribution variable. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Balance Between Anabolism and Catabolism The rate of deposit and withdrawal of energy substrates, and the conversion of 1 type of energy substrate into another; are regulated by hormones. Antagonistic effects of insulin, glucagon, GH, T3, cortisol, and Epi balance anabolism and catabolism. Insert fig. 19.4 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Pancreatic Islets (Islets of Langerhans) Alpha cells secrete glucagon. Stimulus is decrease in blood [glucose]. Stimulates glycogenolysis and lipolysis. Stimulates conversion of fatty acids to ketones. Beta cells secrete insulin. Stimulus is increase in blood [glucose]. Promotes entry of glucose into cells. Converts glucose to glycogen and fat. Aids entry of amino acids into cells. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Energy Regulation of Pancreas Islets of Langerhans contain 3 distinct cell types: a cells: b cells: Secrete glucagon. Secrete insulin. D cells: Secrete somatostatin. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Regulation of Insulin and Glucagon Mainly regulated by blood [glucose]. Lesser effect: blood [amino acid]. Regulated by negative feedback. Glucose enters the brain by facilitated diffusion. Normal fasting [glucose] is 65–105 mg/dl. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Regulation of Insulin and Glucagon (continued) When blood [glucose] increases: Glucose binds to GLUT2 receptor protein in b cells, stimulating the production and release of insulin. Insulin: Stimulates skeletal muscle cells and adipocytes to incorporate GLUT4 (glucose facilitated diffusion carrier) into plasma membranes. Promotes anabolism. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Oral Glucose Tolerance Test Measurement of the ability of b cells to secrete insulin. Ability of insulin to lower blood glucose. Normal person’s rise in blood [glucose] after drinking solution is reversed to normal in 2 hrs. Insert fig. 19.8 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Regulation of Insulin and Glucagon Parasympathetic nervous system: Sympathetic nervous system: Stimulates insulin secretion. GLP-1: Stimulates glucagon secretion. GIP: Stimulates insulin secretion. Stimulates insulin secretion. CCK: Stimulates insulin secretion. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Regulation of Insulin and Glucagon Secretion (continued) Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Glucose homeostasis Insulin Beta cells of pancreas stimulated to release insulin into the blood High blood glucose level STIMULUS: Rising blood glucose level (e.g., after eating a carbohydrate-rich meal) Body cells take up more glucose Liver takes up glucose and stores it as glycogen Homeostasis: Normal blood glucose level (about 90 mg/100 mL) Blood glucose level rises to set point; stimulus for glucagon release diminishes Figure 26.8 Blood glucose level declines to a set point; stimulus for insulin release diminishes Liver breaks down glycogen and releases glucose to the blood STIMULUS: Declining blood glucose level (e.g., after skipping a meal) Alpha cells of pancreas stimulated to release glucagon into the blood Glucagon Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Hormonal Regulation of Metabolism Absorptive state: Absorption of energy. 4 hour period after eating. Increase in insulin secretion. Postabsorptive state: Fasting state. At least 4 hours after the meal. Increase in glucagon secretion. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Absorptive State Insulin is the major hormone that promotes anabolism in the body. When blood [insulin] increases: Promotes cellular uptake of glucose. Stimulates glycogen storage in the liver and muscles. Stimulates triglyceride storage in adipose cells. Promotes cellular uptake of amino acids and synthesis of proteins. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Postabsorptive State Maintains blood glucose concentration. When blood [glucagon] increased: Stimulates glycogenolysis in the liver (glucose-6-phosphatase). Stimulates gluconeogenesis. Skeletal muscle, heart, liver, and kidneys use fatty acids as major source of fuel (hormone-sensitive lipase). Stimulates lipolysis and ketogenesis. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Effect of Feeding and Fasting on Metabolism Insert fig. 19.10 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Diabetes Mellitus Chronic high blood [glucose]. 2 forms of diabetes mellitus: Type I: insulin dependent diabetes (IDDM). Type II: non-insulin dependent diabetes (NIDDM). Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Comparison of Type I and Type II Diabetes Mellitus Insert table 19.6 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Type I Diabetes Mellitus b cells of the islets of Langerhans are destroyed by autoimmune attack which may be provoked by environmental agent. Killer T cells target glutamate decarboxylase in the b cells (see next slide). Glucose cannot enter the adipose cells. Rate of fat synthesis lags behind the rate of lipolysis. Fatty acids converted to ketone bodies, producing ketoacidosis. Increased blood [glucagon]. Stimulates glycogenolysis in liver. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Virus β cells express p69 GAD (expressed by β cells) GABA which regulates glucagon secretion from α cells Without GAD Killer T cells GAD epitope (in β cells) ~ p69 epitope Glucagon secretion from α cells Glc in blood and insulin release Glucagon secretion and blood glc, but no increased insulin because β cells are destroyed. So, glc accumulates. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Consequences of Uncorrected Deficiency in Type I Diabetes Mellitus Insert fig. 19.11 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Type II Diabetes Mellitus Slow to develop. Genetic factors are significant. Occurs most often in people who are overweight. Decreased sensitivity to insulin or an insulin resistance. Obesity. Do not usually develop ketoacidosis. May have high blood [insulin] or normal [insulin]. Insert fig. 19.12 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Treatment in Diabetes Change in lifestyle: Increase exercise: Increases the amount of membrane GLUT-4 carriers in the skeletal muscle cells. Weight reduction. Increased fiber in diet. Reduce saturated fat. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Hypoglycemia Over secretion of insulin. Reactive hypoglycemia: Caused by an exaggerated response to a rise in blood glucose. Occurs in people who are genetically predisposed to type II diabetes. Insert fig. 19.13 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Metabolic Regulation Anabolic effects of insulin are antagonized by the hormones of the adrenals, thyroid, and anterior pituitary. Insulin, T3, and GH can act synergistically to stimulate protein synthesis. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Metabolic Effects of Catecholamines Metabolic effects similar to glucagon. Stimulate glycogenolysis. Stimulate release of glucose from the liver. Stimulate lipolysis and release of fatty acids. NE stimulates b3 receptors in brown fat. Contains uncoupling protein that dissociates electron transport from ATP production. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Metabolic Effects of Catecholamines (continued) Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Metabolic Effects of Glucocorticoids Glucocorticoids secreted in response to release of ACTH. Support the effects of increased glucagon. Promote lipolysis and ketogenesis. Promote protein breakdown in the muscles. Increases blood [amino acids]. Promote liver gluconeogenesis.