Ch6 Metabolism

• Bioregulation of feeding, digestion, and metabolism involves endocrine regulation of feeding and metabolism.
• Endocrine control of digestion: the gut as an endocrine organ.
• The pancreas and glucose homeostasis.
• Control of appetite: orexic and anorexic peptides and the hypothalamus.
• The POMC mutation is absent from other breeds except related flat-coat retrievers.
• The POMC mutation is associated with weight, adiposity, and food motivation in both breeds.
• A POMC mutation is common in the obesity-prone Labrador retriever breed of dog.
• The POMC mutation disrupts b-MSH and b-endorphin production, both implicated in energy homeostasis.
• The hypothalamus is the central control center for feeding behavior.
• Androgens are protein-anabolic, increasing expression of enzymes involved in protein synthesis.
• Short-term signals are long-term signals are satiety signals are adiposity signals.
• Thyroid hormones have ubiquitous effects on metabolism and contribute to optimal activity of many processes.
• Bioregulation of feeding is regulated by endocrine signals from adipose tissue, digestive tract, and bloodstream.
• Other hormones of the endocrine pancreas include Somatostatin (SST, from D cells), which locally inhibits insulin, glucagon & PP secretion in a paracrine way, and Pancreatic peptide (PP, from PP cells), which has a physiological role not yet clear but may function in postabsorptive metabolism stimulated by protein ingestion.
• Paracrine control: Secretion from A cells is inhibited by both insulin and somatostatin, which are released in high glucose.
• Glucagon, GH and corticosteroids are important during fasting, mobilizing stored nutrients and their conversion to more readily utilizable substrates.
• Main nuclei involved in feeding behavior are the ARC, PVN, VMN, DMN, and lateral hypothalamus.
• Orexic agents are anorexic agents are anabolic agents are catabolic agents.
• Further depolarization through closing K ATP channels leads to Na + channel inactivation, smaller action potentials, and reduced secretion.
• Catecholamines, GH & PRL have more specialized functions in intermediary metabolism, such as sudden needs for energy, rapid growth, and secretion of nutrient milk.
• Insulin plays a central role in metabolism, especially when food is freely available, promoting storage of excess nutrients.
• Insulin induces leptin release by adipocytes, inhibiting feeding.
• Insulin binds to tyrosine kinase receptor, occupied receptor phosphorylates several insulin response proteins.
• Glucagon stimulates lipolysis in adipose tissue, leading to increased gluconeogenesis in liver.
• GIP and GLP-1 (incretins) enhance insulin release.
• Glucagon release is controlled by intrinsic control, as A cells have much more active voltage-gated sodium channels than B cells, so membrane is more depolarized.
• Insulin decreases glycogenolysis & lipolysis.
• Insulin increases glucose oxidation, facilitating lipogenesis (adipose tissue) and protein synthesis (muscle), and increases glycogenesis (muscle & liver).
• Insulin release is stimulated by hyperglycemia and parasympathetic neurons (ACh), and is blocked by sympathetic neurons (NE and E).
• Glucagon is a hyperglycemic hormone that is also a conserved peptide (PACAP family), acts through GPCR (Gs-coupled), and promotes glycogenolysis in liver cells, activating glycogen phosphorylase and inhibiting glycogen synthase.
• Insulin release is inhibited by SST (paracrine action), galanin, and pancreostatin.
• Insulin facilitates uptake of glucose into liver, muscle & fat cells (GLUT4) and uptake of amino acids in muscle cells.
• Insulin is a hypoglycemic hormone that is very conserved and phylogenetically old, even in unicellular organisms.
• Somatostatin (SST) is produced by D cells in the stomach and intestine and acts as a paracrine inhibitor of the release of several other GI peptides.
• Glucagon increases glucose in blood and is a hypoglycemic hormone.
• The endocrine pancreas secretes hormones involved in glucose homeostasis, including insulin and glucagon.
• Large smooth muscles enhance absorption of digested products and relax gastric smooth muscle, slowing down gastric processing.
• Cell types in pancreatic islets include B cells, which produce insulin, A cells, which produce glucagon, F cells, which produce PP, and D cells, which produce SST.
• The exocrine pancreas secretes many important proenzymes into the duodenum, including trypsinogen, chymotrypsinogen, lipase, and amylase.
• Anatomically, endocrine cells are found in Islets of Langerhans.