Pancreatic hormones and glucose metabolism Dr.Isabel Hwang Department of Physiology Faculty of Medicine University of Hong Kong May 2007 (isabelss@hkucc.hku.hk)
Pancreatic hormones and glucose metabolism Dr. Isabel Hwang Department of Physiology Faculty of Medicine University of Hong Kong May 2007 (isabelss@hkucc.hku.hk)
Hormones important for glucose metabolism Blood glucose Pancreas Insulin ↓ Glucagon 个 Adrenal Cortisol 个 Epinephrine 个 Pituitary Growth hormone 个
Hormones important for glucose metabolism Blood glucose Pancreas Insulin Glucagon ↓ ↑ Adrenal Cortisol Epinephrine ↑ ↑ Pituitary Growth hormone ↑
Structure of the pancreas 2 major types of tissues 1.acini-secretes digestive juices into the duodenum 2.The islets of Langerhans-secretes insulin and glucagon into blood
Structure of the pancreas 2 major types of tissues 1. acini- secretes digestive juices into the duodenum 2. The islets of Langerhans-secretes insulin and glucagon into blood
The human pancreas bears 1 to 2 million islets of Langerhands with 3 different types of cells Alpha cells-25%of total cells,secrete glucagon Beta cells-60%of total cells,secrete insulin and amylin Delta cells-~10%of total cells,secrete somatostatin PP cells-secretes pancreatic polypeptide
The human pancreas bears 1 to 2 million islets of Langerhands with 3 different types of cells Alpha cells- 25% of total cells, secrete glucagon Beta cells- 60% of total cells, secrete insulin and amylin Delta cells- ~10% of total cells, secrete somatostatin PP cells- secretes pancreatic polypeptide
·Islets are richly vascularised Although islets comprise only 1-2%of the mass of the pancreas,they receive about 10 to 15% of the pancreatic blood flow They are innervated by parasympathetic and sympathetic neurons ·In addition to blood glucose changes, nervous signals also modulate secretion of insulin and glucagon
• Islets are richly vascularised • Although islets comprise only 1-2% of the mass of the pancreas, they receive about 10 to 15% of the pancreatic blood flow • They are innervated by parasympathetic and sympathetic neurons • In addition to blood glucose changes, nervous signals also modulate secretion of insulin and glucagon
Structure of insulin Small protein,with a molecular weight(about 6000Da) 2 chains (A-21 a.a.;B- 30a.a.) Amino acid sequence is highly conserved among vertebrates, Bowre Insu many diabetic patients are treated with insulin extracted from pig and cow pancreases
Structure of insulin • Small protein, with a molecular weight (about 6000 Da) • 2 chains (A- 21 a.a.; B- 30 a.a.) • Amino acid sequence is highly conserved among vertebrates, many diabetic patients are treated with insulin extracted from pig and cow pancreases
Insulin and glucagon are critical participants in glucose homeostasis and serve as acute regulators of blood glucose concentration
• Insulin and glucagon are critical participants in glucose homeostasis and serve as acute regulators of blood glucose concentration
Physiological effects 1.Carbohydrate Metabolism Insulin promotes muscle glucose uptake and metabolism Normal resting muscle membrane is not highly permeable to glucose,except when stimulated by insulin Insulin stimulates glycogen storage in muscle Insulin facilitates glucose transport through the muscle cell membrane Insulin promotes liver uptake,liver storage and use of glucose Insulin promotes conversion of excess glucose into fatty acids and inhibits gluconeogenesis in the liver
Physiological effects 1. Carbohydrate Metabolism - Insulin promotes muscle glucose uptake and metabolism - Normal resting muscle membrane is not highly permeable to glucose, except when stimulated by insulin - Insulin stimulates glycogen storage in muscle - Insulin facilitates glucose transport through the muscle cell membrane - Insulin promotes liver uptake, liver storage and use of glucose - Insulin promotes conversion of excess glucose into fatty acids and inhibits gluconeogenesis in the liver
Mechanism of increased glucose uptake and liver storage by insulin 1.Insulin inactivates liver phosphorylase,the enzyme that converts glycogen to glucose 2.Insulin enhanced uptake of glucose from the blood by increasing activity of an enzyme called glucokinase(to phosphorylates glucose after it diffuses into liver cells) 3. Insulin stimulates the activity of glycogen synthase which promotes glycogen synthesis Net effect:To increase amount of glycogen in liver
Mechanism of increased glucose uptake and liver storage by insulin 1. Insulin inactivates liver phosphorylase, the enzyme that converts glycogen to glucose 2. Insulin enhanced uptake of glucose from the blood by increasing activity of an enzyme called glucokinase (to phosphorylates glucose after it diffuses into liver cells) 3. Insulin stimulates the activity of glycogen synthase which promotes glycogen synthesis Net effect: To increase amount of glycogen in liver
Insulin-independent effect The brain cells normally use glucose for energy Therefore,the brain cells are permeable to glucose and can utilize glucose independently of the effect exerted by insulin
Insulin-independent effect • The brain cells normally use glucose for energy • Therefore, the brain cells are permeable to glucose and can utilize glucose independently of the effect exerted by insulin