Ch. 4.4 Hormonal Regulation of Carbohydrate Metabolism & Hunger - Slides PDF

Hormonal Reg. of Carbohydrates  Endocrine Regulation of Metabolism Glucose must be available to tissues. Glycogenolysis (glycogen  glucose or G6P) Gluconeogenesis (FFAs, AAs, lactate pyruvate  glucose) Insulin: Lowers blood glucose.  Counters hyperglycemia, opposes glucagon. ...

Hormonal Reg. of Carbohydrates  Endocrine Regulation of Metabolism Glucose must be available to tissues. Glycogenolysis (glycogen  glucose or G6P) Gluconeogenesis (FFAs, AAs, lactate pyruvate  glucose) Insulin: Lowers blood glucose.  Counters hyperglycemia, opposes glucagon.  Facilitates glucose transport into cells.  Enhances synthesis of glycogen, protein, fat.  Inhibits gluconeogenesis. Glucagon: Raises blood glucose.  Countershypoglycemia, opposes insulin.  Promotes glycogenolysis, gluconeogenesis. 2  Pancreatic Hormones Two different types of tissues, acini and islets of Langerhans compose the pancreas  The islets are comprised of about 20% α-cells that secrete glucagon and 75% β-cells that secrete insulin  Glucagon & insulin are both peptide hormones  The acini serve an exocrine function and secrete digestive enzymes Fig. 20.16. McArdle et al. 2010. Exercise Physiology… LWW  Glucagon The α-cells of the islets of Langerhans secrete glucagon, the “insulin antagonist” hormone, in response to low [glucose] Primarily stimulates both glycogenolysis and gluconeogenesis by the liver and increases lipid catabolism Plasma glucose concentration controls glucagon output by the pancreas Fig. 20.16. McArdle et al. 2010. Exercise Physiology… LWW  Glucagon & cAMP Pathway  Glucagon binds to receptor  Stimulates adenylate cyclase to convert ATP to cAMP  cAMP activates PKA (protein kinase A)  PKA phosphorylates (and thus Adenylate activates) glycogen LIVER CELL Cyclase phosphorylase (hepatocyte)  Glycogen phosphorylase initiates glycogenolysis and cleaves a G6P from glycogen  G6P converted back to glucose (only in liver) Inactive glycogen Glycogen  Glucose can leave liver to phospohorylase phospohorylase restore blood [glu] Blood Glucose Glucose-6 Glucose-6- Glycogen phosphatase phosphate Glucose 5  Insulin decreases glucose Insulin regulates glucose entry into all tissues (primarily muscle and adipose) except the brain Insulin exerts a hypoglycemic effect by reducing blood glucose concentration 2nd messengers (PI-3 kinase pathway) stimulate GLUT transporters (GLUT4 in muscle) to translocate to the plasma membrane  Glucose then enters via facilitated diffusion  http://www.youtube.com/watch?v=OlHez8gwMgw (1:40)  Insulin’s anabolic effects Insulin is also considered an anabolic hormone because it also triggers a different 2nd messenger system (mTOR pathway) to stimulate protein synthesis Importanceof post-exercise CHO consumption In addition to glycogen replenishment Insulin-Mediated Glucose Uptake PI-3 Kinase Pathway *You do NOT need to know 8 these details!  Impaired Glucose Homeostasis A defect anywhere along the pathway for glucose uptake signals diabetes; possible causes include: Destructionof β -cells (Type 1 Diabetes) Type 2 Diabetes (insulin resistant) includes: Altered insulin receptors or a decreased number of receptors on peripheral cells Defective processing of the insulin message or an interruption in that PI-3 kinase signaling pathway Abnormal insulin synthesis or depressed insulin release https://www.youtube.com/watch?v=HJGjNTJgf48 (to 7 min)  Regulation of Carbohydrate Metabolism During Exercise Adequate glucose during exercise requires glucose release by liver and glucose uptake by muscles  Amount of glucose released from liver depends on exercise intensity and duration. Some hormones increase circulating glucose:  Glucagon  Epinephrine  Norepinephrine  Cortisol Circulating glucose during exercise is also affected by the following:  GH: FFA mobilization, cellular glucose uptake  T3, T4: glucose catabolism and fat metabolism 10  Regulation of Carbohydrate Metabolism During Exercise As exercise intensity increases, catecholamine release increases which increases glycogenolysis rate (liver & muscles)  Muscle glycogen is used before liver glycogen As exercise duration increases, more liver glycogen is used muscle glucose uptake  liver glucose release  as glycogen stores , glucagon levels 11  Hormonal & Glucose Changes Fig. 4.4. Kenney et al. 2019. Physiology of 12 Sport & Exercise. Hum.Kin.  Changes in Glucose & Insulin Fig. 4.5. Kenney et al. 2019. Physiology of 13 Sport & Exercise. Hum.Kin.  Regulation of Carbohydrate Metabolism During Exercise Glucose mobilization is only half the story. At rest, insulin enables glucose uptake in muscle. During exercise,  insulin concentrations decrease;  cellular insulin sensitivity increases; and  more glucose is taken up into cells utilizing the AMPK pathway (AMP-activated protein kinase) AMPK does NOT require insulin to move GLUT4 14 Exercise-Mediated Glucose Uptake 15  Glycemic Control During Exercise Skeletal muscle consumes the major amount of glucose transported in blood A single bout of moderate or intense physical activity abruptly decreases plasma glucose levels, an effect that persists for up to several days The immediate effects of each exercise session on increasing the active muscles’ insulin sensitivity causes long-term improvement in glycemic control Improved insulin sensitivity with regular physical activity provides type 2 diabetics with important “therapy” that ultimately lowers their insulin requirement  Glycemic Control During Exercise Factors account for the improved insulin sensitivity for glucose transport in skeletal muscle and adipose tissue after a bout of physical activity:  Translocation of GLUT-4 from the endoplasmic reticulum to the cell surface  Increase in total quantity of GLUT-4  Increase in glycogen synthase activity and subsequent glycogen storage Combining resistance exercise and endurance training improves markers of insulin resistance and body composition for insulin- resistant individuals more than endurance training Hunger Hormones  Regulating Caloric Intake The hypothalamus is the brain’s appetite control center.  Satiety center in ventromedial nucleus Leptin  Hunger center in lateral hypothalamus Ghrelin  Leptin and ghrelin act in opposing ways to aid in energy balance. 19  Leptin & Satiety Peptide hormone secreted by adipose tissue to signal satiety  Utilizes JAK/STAT pathway to signal hypothalamus to ↓ appetite Leptin level proportional to body fat (~4x higher in obese)  Why do obese individuals struggle with overeating? Leptin resistance? Fig. 30.6. McArdle et al. 2010. Exercise No Ob gene Physiology… LWW  GI Tract Hormones GI tract releases hormones that affect hunger signals. Ghrelin: Peptide hormone that Increases appetite. Cholecystokinin (CCK): Is stimulated when stomach is full; Peptide hormone that decreases appetite. Glucagon-like peptide 1 (GLP-1): Is released in small intestine; decreases appetite. Peptide YY (PYY): Is released in small intestine; decreases appetite. Exercise affects hunger and satiety hormones. Acute, vigorous exercise increases PYY and GLP-1, reducing hunger. 21  Review Questions Explain glucagon’s role in regulating blood glucose.  Create a negative feedback diagram to explain it  Include steps of cAMP signaling Explain insulin’s role in regulating blood glucose using negative feedback and the PI3-kinase pathway Discuss how exercise is beneficial for diabetics by explaining the AMPK pathway Compare & contrast the roles of leptin & ghrelin in regulating hunger. 22  Figure & Notes References Kenney, Wilmore, Costill. Physiology of Sport and Exercise (7th ed). Human Kinetics, 2018. McCardle, Katch, Katch. Exercise Physiology: Nutrition, Energy, and Human Performance, 8th Edition. Wolters Kluwer Health, 2014. Baechle & Earle. Essentials of Strength & Conditioning, 4th Edition. Human Kinetics, 2016. 23