NUTR 470 1st Edition Lecture 10-The Integrative Regulation of Glucose Homeostasis-Major flux of glucose metabolism in liver cells-In the liver, the NET outcome of glucose fluxes determines glucose production, and thereby plasma levels of glucose• alpha Islet cells produce glucagon; Beta islet cells produce insulin (in the pancreas)-signals that regulate glucose homeostasis— glucagon and insulin--Integrative Regulation of Glucose Homeostasis• At the cellular level— Four major glucose fluxes are cooperatively regulated.• At the whole body level— Multiple tissues/organs are participating in the coordinated regulation to achieve whole body glucose homeostasis.— pancreas, liver-- Feeding• Digestion and absorption of food result in elevations in the levels of glucose.• Under physiological conditions, feeding or fasting triggers the integrative regulation.• Glucose, at high levels, stimulates the secretion of insulin and turns down the secretion of glucagon.-- Fasting• Glucose levels return to the lower levels of normal range.• The reduction in glucose levels stimulates the secretion of glucagon and turns down the secretion of insulin.• Under physiological conditions, feeding or fasting triggers the integrative regulation.- Stimuli• Under physiological conditions, the excitement of sympathetic nervous system is also involved in the integrative regulation.-Nervous, exciting, anxious, stress-Fighting-Emerging reactions• Stimuli cause an increase in epinephrine.- Stressors• In response to acute stress, the pituitary-adrenal axis is participating in the integrative regulation. -Injury, damage, trauma• Loss of blood— leads to the secretion of epinephrine— which is why you need to put pressure on the wound so blood stays in and there is enough pressure to get blood to the brain.-Fever, infection-Angry• Stressors cause an increase in glucagon, glucocorticoid, and etc.- Promoting glucose storage-Changes in nutritional and hormonal factors are to regulate glucose metabolism at the integrative level.-Glucose, insulin-Glucagon, epinephrine, glucocorticoid— provide signals so the brain gets energy-Nutritional and hormonal factors are integrated as changes in the activities of enzymes that are related to glucose metabolism.• Promoting glucose utilization/storage-HK/GK, 6PFK1, GS-HK/GK— think about muscle cells— glucose transport, helping with glycogen synthesis • Promoting glucose production-PEPCK, FBPase, G6Pase, GP-G6Pase— powerful activator for glycogen synthesis• These are driven by the same signals-The integrative regulation of glucose homeostasis is achieved through coordinating glucose metabolic fluxes. • Promoting glucose utilization/storage-Glycolysis and glycogenesis• Promoting glucose production-Gluconeogenesis and glycogenolysis- Coordinated Regulation of Glucose Homeostasis-Key points for coordination• When glucose is in excess, there should be an increase in glucose utilization/storage (glycolysis/glycogenesis).• When glucose is not enough, there should be an increase in gluconeogenesis/glycogenolysis in the liver – producing glucose.• Glucose, at high levels, stimulates the secretion of insulin and inhibits the secretion of glucagon.• Stress and emerging reactions (sympathetic excitement) stimulate the secretion of epinephrine – glucose is needed!-Summary• Glucose metabolic pathways• Integrative regulation• Regulation of a single pathway• Roles of nutritional, hormonal signals• Regulation of two or more