Section V. Carbohydrate metabolismSection V cont.Insulin vs. glucagon V.10Chapt. 26 hormone regulationInsulin vs glucagon and othersGlucagon mobilizes glucose from tissuesFuel homeostasishomoeostatisInsulin is anabolicGlucagon is fuel metabolismPancreasHigh-carbohydrate mealTable 1 Insulin and counterregulatory hormonesInsulin counterregulatory hormonesIII. Synthesis and release of insulin and glucagonRelease of insulin by b-cellsTable 26.2 Regulators of insulin releaseTable 26.3 Regulators of Glucagon releaseEffect of high-protein mealMechanisms of hormone actionsPlasma membrane hormone receptorsRTK Insulin receptor has several signaling pathsSignal transduction by insulinSignal transduction by glucagonSignal transduction by cortisol, intracellular receptorsSignal transduction by epinephrine, norepinephrineKey conceptsReview questionsSection V. Carbohydrate metabolismV. Glucose is central to all metabolism•3 major paths: glycolysis, glycogen synthesis and pentose phosphate (generates NADPH, 5-C sugars) (V.2)•Major diet carbohydrates (starch, sucrose, lactose) are digested to glucose, fructose and galactose (V.1)•Fructose and galactose are converted to intermediates in glucose metabolism (V.3)•Glycolysis plus TCA, ETC; anerobic glycolysis (V.4)•Intermediates in glycolysis, TCA serve biosynthesis of amino acids, fatty acids, glycerol (V.5)Section V cont.•Pentose phosphate path takes glucose to pyruvate: forms NADPH (use for biosynthesis, antioxidant) forms 5-C sugars used for nucleotides (v.6)•UDP-glucose is used in synthesis of glycogen, UDP-galactose, also glycoproteins, glycolipids (V.7)•Glycogenolysis degrades glycogen → glucose•Gluconeogenesis → glucose from glycerol (V.8)•Overview of major paths of glucose metabolism (V.9)•Hormonal control: glucagon vs. insulin to maintain glucose homeostasis (V.10)Insulin vs. glucagon V.10V.10 Pathways regulated by glucagon vs. insulin in response to blood glucose (tissue-specific also)Blood glucose decrease → Glucagon release → ↑glycogenolysis ↑gluconeogenesis ↑lipolysis ↓liver glycolysis Blood glucose increase → Insulin release → ↑glycogen synthesis ↑fatty acid synthesis ↑triglyceride synthesis ↑liver glycolysisChapt. 26 hormone regulationCh. 26 Regulation by Insulin, glucagon and other hormonesStudent Learning Outcomes:•Describe mechanisms of major hormones insulin and glucagon to control glucose homeostasis•Explain that Homeostasis is balance of fuel mobility and storage: keep glucose 80-100 mg/dL (~5 mM)•Regulate carbohydrate, lipid, aa metabolism•Describe counteracting influences of insulin and glucagon and other counter-regulatory hormonesInsulin vs glucagon and othersFig. 2 Homeostasis requires glucose control:Insulin is anabolic hormone:•from -cells of pancreas•Glucose entry into tissues•Glucose storage, growthGlucagon counters:•Degradation of glycogen•Gluconeogeneis•Mobilize fatty acids•Stress hormones counter:•Epinephrine, •Cortisol (glucocorticoid)Glucagon mobilizes glucose from tissuesFig. 1, 3 Glucagon activates pathways for glucose mobilization:•Counteracts insulin•Pancreas -cell•Acts via G-protein-coupled receptor,cAMP, PKAFuel homeostasisFig. 4 Fuel homeostasis requires balance:•Substrate availability and need•Concentration nutrients in blood affects storage•Hormonal messages to target tissue•Neuronal signalshomoeostatisGlucose homeostasis is critical:•Multiple signals•Insulin vs. glucagon•Stress hormones•Epinephrine•CortisolFig. 5Insulin is anabolicFig. 6; + stimulated by insulin; -, inhibited Insulin is major anabolic hormone for fuel storage:•Storage as glycogen•Synthesis of fatty acids•Triacylglycerol storage•Protein synthesis•Tissues of actionGlucagon is fuel metabolismGlucagon is major hormone for fuel metabolism:•Maintain fuel in absence of dietary glucose•Glycogenolysis in liver•Gluconeogenesis in liver•Fatty acids from adipocytes•Tissues of actionFig. 7; + stimulated by glucagon; -, inhibitedPancreas Pancreas has  and  cells cells make insulin;  cells make glucagonHigh-carbohydrate mealHigh-carbohydrate meal:•Rapid increase of glucose•80 → >120 mg/dL •Rapid increase of insulin•5 → >120 U/mL•Decrease of glucagon•110 → 90 pg/mLFig. 8 Blood levels after mealTable 1 Insulin and counterregulatory hormonesHormone functions major metabolic pathsInsulin promotes storage stimulate glucose storage inmuscle, liverpromotes growth stimulates protein synthesis, fatty acid synthesisGlucagon mobilizes fuels activates gluconeogenesis and glycogenolysismaintains blood activates fatty acid release glucose in fastingEpinphrine mobilizes fuels stimulate glycogenolysis in acute stress stimulate fatty acid releaseCortisol changing long term amino acid mobilizationgluconeogenesisInsulin counterregulatory hormonesFig. 9 Major insulin counterregulatory hormones:Stress of low glucose:•Neuronal signals release hormones:•ACTH from pituitary→•Cortisol from adrenal cortex•Epinephrine from adrenal medulla•Norepinephrine from nerves•Minor role release glucagonIII. Synthesis and release of insulin and glucagonFig. 10insulin Insulin is polypeptide of 51 amino acids:•  and chains, cross-linked•Synthesized as preproinsulin, cleaved in RER to proinsulin•Passed through Golgi, into storage vesicles (also Zinc)•Final protease cleavages forms active insulin•Exocytosis into blood is stimulated by increased glucose in blood around -cellsRelease of insulin by  -cellsRelease of insulin by -cells:•Stimulated by increased glucose in blood around -cells•Glucose enters through transporters (GLUT 2)•Hexokinase phosphorylates, TCA, ETC•ATP ↑; inhibit ATP-dep K+ channel•Membrane depolarization •Ca2+ channel opens•[Ca2+] stimulate vesicle fusionFig. 11 release of insulin in response to increased blood glucoseTable 26.2 Regulators of insulin releaseRegulators of insulin release:Major regulators: Effect: Glucose + threshhold ~80 mg/dL, increase proportional to ~300 mg/dL Insulin is removed from blood and degraded in liver New synthesis of insulin occurs in -cells after release Minor regulators: Amino acids + Neural input + Gut hormones + (chapt. 43)Table 26.3 Regulators of Glucagon releaseRegulators of glucagon release:Major regulators: Effect: Glucose - Insulin -Amino acids +Minor regulators: Cortisol +