Regulation of Energy Metabolism (PDF)

Sumathy Arumugam  SUB-TOPICS ◦ The brain and energy metabolism* ◦ Glucagon and insulin – 22/10/2021 ◦ Creatine phosphate ◦ Creatinine ◦ Glycogen ◦ Gluconeogenesis ◦ Fructose ◦ Fatty acids ◦ The Krebs cycles* ◦ Fermentative and aerobic metabolism*  INTRODUCTION ◦ Insulin and glucagon are ho...

Sumathy Arumugam  SUB-TOPICS ◦ The brain and energy metabolism* ◦ Glucagon and insulin – 22/10/2021 ◦ Creatine phosphate ◦ Creatinine ◦ Glycogen ◦ Gluconeogenesis ◦ Fructose ◦ Fatty acids ◦ The Krebs cycles* ◦ Fermentative and aerobic metabolism*  INTRODUCTION ◦ Insulin and glucagon are hormones that help to regulate the levels of blood glucose, or sugar, in the body. ◦ Glucose, which comes from the food, moves through the bloodstream to help fuel our body. ◦ Insulin and glucagon work together to balance the blood sugar levels, keeping them in the narrow range that our body requires.  LEARNING OUTCOMES On successful completion of the lesson, the student will be able to: ◦ describe the biological actions of insulin and glucagon; ◦ list the major target organs for insulin; ◦ identify the effect of insulin on the target organs; ◦ describe the control of glucagon secretion; ◦ identify the target organ for glucagon.  DESCRIPTION ~ INSULIN ◦ The endocrine cells of the pancreas are located in islets. ◦ The islets contain four distinct cell types, each secreting a different peptide hormone. ◦ Approximately 75% of the islet cells are beta (β) cells which produce insulin. ◦ Another 20% are alpha (α) cells that secrete glucagon. ◦ The delta (δ) cells produce the paracrine, somatostatin (SRIF). Which inhibits both insulin and glucagon secretion.  DESCRIPTION ~ INSULIN ◦ Insulin is secreted from the pancreas by a process called glucose stimulated insulin secretion (GSIS)  DESCRIPTION ~ INSULIN ◦ Insulin is secreted in a biphasic manner. The initial burst reflects the release of preformed secretory vesicles; it lasts 5-15 minutes. The second more gradual and sustained secretion (30min) is due to the release of newly synthesized insulin molecules. ◦ The half life of insulin, like most protein hormones, is short (~ 5 minutes). ◦ Most of secreted insulin is degraded by the liver and kidney. ◦ Insulin secretion is regulated by factors other than glucose. Both an increase in plasma amino acids and the feed forward signaling by glucagon like peptide from the small intestine will lead to secretion of insulin. DESCRIPTION ~ INSULIN Effects of insulin The primary targets for insulin are liver, skeletal muscle and fat. Insulin has multiple actions in each of these tissues, the net result of which is fuel storage (glycogen or fat). Glucose enters the circulation either from the diet or from synthesis in the liver. It enters all cells via the glucose transporter (GLUT). To prevent glucose from leaving the cells via this transporter, the glucose is rapidly phosphorylated to glucose-6-phosphate. DESCRIPTION ~ INSULIN ◦ Effects of insulin (cont.) There is a family of glucose transporters (e.g., GLUT 1, GLUT 2, GLUT 4). In skeletal muscle and fat cells, insulin binds to the insulin receptor which causes the active recruitment of the glucose transporter, GLUT 4, to the cell surface. Once located at the cell surface, GLUT 4 increases the amount of glucose that enters fat and skeletal muscle cells. The GLUT 4 action enables a rapid removal of glucose from the circulation thereby restoring plasma levels to 4.4-5.5 mmol/L (80-100 mg/dL).  DESCRIPTION ~ INSULIN ◦ Insulin deficiency Problems arise from: Reduced glucose uptake into various tissues (energy starvation) Increased release of glucose from the liver (hyperglycemia) The effect of these two deficiencies is simple: Too little glucose inside cells Too much glucose in the blood (hyperglycemia)  DESCRIPTION ~ INSULIN ◦ Insulin deficiency Problems arise from: Reduced glucose uptake into various tissues (energy starvation) Increased release of glucose from the liver (hyperglycemia) The effect of these two deficiencies is simple: Too little glucose inside cells Too much glucose in the blood (hyperglycemia) Positive and negative regulation of secretion by the pancreatic beta cell DESCRIPTION ~ GLUCAGON ◦ Glucagon is a peptide hormone secreted from the pancreatic islet alpha cells when glucose levels are less than 4.4 mmol/L or 80 mg/dL. ◦ Glucagon circulates unbound in the plasma; it has a half- life of 6 minutes. ◦ Glucagon is a peptide hormone. DESCRIPTION ~ GLUCAGON ◦ Glucagon binds a plasma membrane receptor which initiates a second messenger signaling cascade. ◦ The target tissue for glucagon is the liver. ◦ Glucagon causes the liver to secrete glucose leading to a net decrease in stored glycogen and an increase in plasma glucose. ◦ In the absence of insulin, glucagon is secreted. ◦ Glucagon acts in a synergistic manner with cortisol and epinephrine to raise blood glucose levels DESCRIPTION ~ GLUCAGON  SUMMARY ◦ Endocrine pancreas produces insulin and glucagon which regulate fuel homeostasis in the fed and fasted states, respectively. ◦ Insulin is secreted primarily in response to an increased blood glucose level. Glucagon is secreted in response to decreased blood glucose level. ◦ In the fed state, insulin directs the storage of excess nutrients in the form of glycogen, triglycerides, and protein. The targets of insulin are liver, muscle, and adipose tissue. ◦ In the fasting state, glucagon directs the movement of stored nutrients into the blood. Liver is the main physiological target of glucagon. SUMMARY