Lecture 24 2024-03-15 Metabolic Hormones PDF

Outline Learning Objectives: Introduction: anabolism vs. catabolism ✔ Carbohydrate, lipid and protein metabolism ✔ Metabolic rate (MR) ✔ Factors affecting metabolic rate (e.g. size, activity, temperature, hormones) ✔ ✔ Metabolism ✔ 25 Metabolic hormones Insulin and glucagon – Endocrine Pancreas (duc...

Outline Learning Objectives: Introduction: anabolism vs. catabolism ✔ Carbohydrate, lipid and protein metabolism ✔ Metabolic rate (MR) ✔ Factors affecting metabolic rate (e.g. size, activity, temperature, hormones) ✔ ✔ Metabolism ✔ 25 Metabolic hormones Insulin and glucagon – Endocrine Pancreas (duct cell) Fig. 14-15, p683 (duct cell) Metabolism 26 Metabolic hormones Insulin - peptide hormone that is synthesized in the pancreas within β-cells of the islets of Langerhans Functions: ↑ glucose uptake in muscle and adipose tissue ↑ glucose uptake in liver (indirectly) ↑ glycogenesis in liver and muscle ↓ glycogenolysis ↓ gluconeogenesis ↑ uptake of fatty acids and triglycerides (TAGs) by fat cells ↑ lipogenesis (from glucose) ↓ lipolysis ↓ ketone bodies ↑ uptake of amino acids by muscle and liver ↑ protein synthesis and ↓ protein degradation ANABOLIC Metabolism 27 Metabolic hormones Insulin - peptide hormone that is synthesized in the pancreas within β-cells of the islets of Langerhans Functions: ↑ glucose uptake in muscle and adipose tissue ↑ glucose uptake in liver (indirectly) ↑ glycogenesis in liver and muscle ↓ glycogenolysis ↓ gluconeogenesis ↑ uptake of fatty acids and triglycerides (TAGs) by fat cells ↑ lipogenesis (from glucose) ↓ lipolysis ↓ ketone bodies ↑ uptake of amino acids by muscle and liver Controlled indirectly via ↑ protein synthesis and ↓ protein degradation regulation of various enzymes in metabolic pathways Metabolism 28 Metabolic hormones Insulin – Glucose Uptake Action - glucose transporter (GLUT) systems - mediate facilitated diffusion (i.e. transports glucose and closely related monosaccharides down their concentration gradients) - different isoforms of GLUTs are expressed in a tissue-specific pattern (e.g. GLUT1, GLUT3 in brain; GLUT2 in liver, kidney, intestine, pancreatic β-cells; GLUT4 in muscle, adipose) ➥ all cells express at least one isoform Metabolism 29 Metabolic hormones Insulin – Glucose Uptake Action - in resting skeletal muscle and adipose tissue, insulin increases glucose uptake by receptor tyrosine kinase activation ➥ insulin increases the number of GLUT4 on the plasma membrane, thereby increasing glucose uptake in these cells Absence of insulin, glucose does not enter the cell Metabolism (receptor tyrosine kinase) Insulinreceptor binding facilitates glucose to enter the cell GLUT-4 30 Metabolic hormones Insulin – Glucose Uptake Action - in hepatocytes, glucose uptake is indirectly regulated by insulin ➥ liver cells have GLUT2 (instead of GLUT4) transporters - in a fed state, insulin activates hexokinase (HK), the first enzyme in the glycolytic pathway that converts glucose to glucose-6-phosphate ➥ activating HK will keep glucose levels low in the hepatocytes and maintain a concentration gradient for glucose transport Hepatocytes transport glucose out during fasted state Insulin receptor tyrosine kinase Insulin activates HK to convert glucose to G-6-P during fed state Insulin receptor tyrosine kinase HK Metabolism 31 Metabolic hormones Glucagon - peptide hormone that is synthesized in the pancreas within α-cells of the islets of Langerhans Functions: ↑ release of glucose into blood ↓ glycogenesis in liver cells ↑ glycogenolysis in liver cells ↑ gluconeogenesis in liver cells ↑ release of amino acids by ↑ protein degradation and ↓ protein synthesis in liver ↑ release of fatty acids by ↓ lipogenesis and ↑ lipolysis in adipose tissue ↑ ketone production CATABOLIC Metabolism 32 Metabolic hormones Glucagon - peptide hormone that is synthesized in the pancreas within α-cells of the islets of Langerhans Functions: ↑ release of glucose into blood regulated indirectly via activation ↓ glycogenesis in liver cells or deactivation of various ↑ glycogenolysis in liver cells enzymes in metabolic signal ↑ gluconeogenesis in liver cells transduction pathways ↑ release of amino acids by ↑ protein degradation and ↓ protein synthesis in liver ↑ release of fatty acids by ↓ lipogenesis and ↑ lipolysis in adipose tissue ↑ ketone production Metabolism 33 Metabolic hormones Pancreatic Hormones and Metabolism anabolism > catabolism catabolism > anabolism Overall goal: to maintain blood glucose levels Metabolism 34 Metabolic hormones Daily Metabolic Cycle - the body alternates between the fed (absorptive) state and the fasted (post-absorptive) state Fed (absorptive) state: ➨ dominated by insulin ➥ ingested nutrient molecules are absorbed into the blood ➥ glucose is mostly used to supply various energy needs of the body ➥ net synthesis of proteins, glycogen, and fat Metabolism 35 Metabolic hormones Daily Metabolic Cycle Fed (absorptive) state: ➨ dominated by insulin Metabolism 36 Metabolic hormones Daily Metabolic Cycle Post-absorptive (fasted) state: ➨ dominated by glucagon ➥ occurs 3-5 hours after absorptive phase, when digestive tract is empty of nutrients & available pool of nutrients in blood decreases ➥ only brain, nervous system, muscle relies on glucose for energy; most other body cells use fatty acids and ketones for energy ➥ net degradation of proteins, glycogen and fat Metabolism 37 Metabolic hormones Daily Metabolic Cycle Post-absorptive (fasted) state: ➨ dominated by glucagon glycogenolysis provides glucose fuel for skeletal muscle glycogenolysis and gluconeogenesis in the liver provide plasma glucose for nervous tissue lipolysis supplies lipids to fuel all other cells Metabolism 38 Metabolic hormones Daily Metabolic Cycle 24-Hour Human Glucagon and Insulin Levels: Metabolism 39 Metabolic hormones Daily Metabolic Cycle Human Insulin, Glucagon and Nutrient Levels: Absorptive state Metabolism meal 40 Metabolic hormones Daily Metabolic Cycle Human Insulin, Glucagon and Nutrient Levels: Postabsorptive state Metabolism meal 41 Metabolic hormones Daily Metabolic Cycle Human Insulin, Glucagon and Nutrient Levels: Acute starvation Metabolism meal 42 Metabolic hormones Daily Metabolic Cycle Human Insulin, Glucagon and Nutrient Levels: Chronic starvation - well-fed 70 kg human ➥ fuel reserves of about 161,000 kcal ➥ energy needed for a 24 h period about 1,600 – 6,000 kcal ➥ Glycogen reserves are exhausted in 1 day ➥ Sufficient reserves for up to 1 – 3 months of starvation Metabolism meal 43 Metabolic hormones Daily Metabolic Cycle Human Insulin, Glucagon and Nutrient Levels: Chronic starvation - first priority: provide sufficient glucose to brain and other critical tissues - second priority: preserve protein ➥ shift from utilization of glucose to fatty acids and ketone bodies ➥ mobilization of TAGs in adipose + gluconeogenesis by liver to use fatty acids as fuel - after several weeks of starvation ➥ ketone bodies major fuel of brain - after depletion of TAG stores ➥ protein degradation accelerates ➥ death due to loss of heart, liver, and/or kidney function Metabolism 44 Metabolic hormones Daily Metabolic Cycle Factors Influencing Insulin and Glucagon Secretion Fig. 7-26, p321 ↑ blood glucose: ↑ insulin secretion, ↓ glucagon secretion Fed/Absorptive State Metabolism 45 Metabolic hormones Daily Metabolic Cycle Factors Influencing Insulin and Glucagon Secretion Fig. 7-26, p321 ↓ blood glucose: ↓ insulin secretion, ↑ glucagon secretion Fasted/Post-absorptive State Metabolism 46 Metabolic hormones Factors Influencing Insulin and Glucagon Secretion ↑ blood glucose: ↑ insulin secretion, ↓ glucagon secretion ↓ blood glucose: ↓ insulin secretion, ↑ glucagon secretion ↑ amino acids in blood: ↑ insulin secretion ↑ fatty acids: ↑ insulin secretion, ↓ glucagon Fig. 7-25, p319 ↑ parasympathetic activity: ↑ insulin secretion ↑ sympathetic activity: ↓ insulin secretion, ↑ glucagon secretion ↑ Incretins (e.g. GIP, glucose-dependent insulinotropic peptide): ↑ insulin secretion Metabolism 47