Fuel Metabolism & Pancreatic Hormones PDF

Endocrine control of fuel metabolism, pancreatic hormones Andrea C. Gore, PhD Professor, Division of Pharmacology and Toxicology [email protected] 1 By the end of this lecture you will understand: Intermediary (fuel) metabolism Pancreatic endocrine hormones Insulin Glucagon Other metabol...

Endocrine control of fuel metabolism, pancreatic hormones Andrea C. Gore, PhD Professor, Division of Pharmacology and Toxicology [email protected] 1 By the end of this lecture you will understand: Intermediary (fuel) metabolism Pancreatic endocrine hormones Insulin Glucagon Other metabolic hormones involved in fuel metabolism 2 Lipogenesis Lipolysis Glycogenolysis Glycogenesis Gluconeogenesis Anabolism Catabolism Hydrolysis Oxidation Ketosis Genesis: generation of something Neogenesis: generating something new from something different Lysis: breakdown 3 Metabolism: all chemical reactions that occur within body cells. Fuel metabolism (= intermediary metabolism) includes reactions involving the degradation, synthesis, and transformation of the three classes of energy-rich organic molecules: 1. Protein -> amino acids 2. Carbohydrate -> monosaccharides (mainly glucose) 3. Fat (triglycerides) -> monoglycerides Digestion is the process of breaking down large nutrient molecules (macromolecules) into smaller absorbable units that are transferred into the blood. 4 ¡ Anabolism: buildup or synthesis of larger organic macromolecules from small organic molecular subunits. § Typically requires adenosine triphosphate (ATP) § Reaction results in: (1) manufacture of materials needed by the cell, or (2) the storage of excess ingested nutrients. ¡ Catabolism: breakdown of large, energy-rich organic molecules within cells. § Two levels: (1) hydrolysis of large cellular macromolecules into smaller units, and (2) oxidation of smaller subunits, such as glucose, to yield energy for ATP 5 Food intake is intermittent, requiring energy storage for use between meals. 3 forms of energy storage: 1. 1st energy source: excess circulating glucose is stored in liver and muscle as glycogen – 1% body energy content 2. Primary energy reservoir: free fatty acids from fat that are stored as triglycerides in adipose tissue – 77% of the body energy content (2 months storage reservoir) 3. Secondary energy reservoir: amino acids are stored in muscle as proteins – 22% of the body energy 6 ¡ Liver § Primary role in maintaining normal blood glucose levels § Principal site for metabolic interconversions such as gluconeogenesis ¡ Adipose tissue § Primary energy storage site § Important in regulating fatty acid levels in the blood ¡ Muscle § Primary site of amino acid storage § Major energy user ¡ Brain § Normally can only use glucose as an energy source § Does not store glycogen 7 Interconversions & Fate of Nutrients Energy Fats Urine Ketones Carbohydrates Plasma fatty acid lipolysis Gluconeogenesis Plasma glucose Fat Stores triglycerides (adipose tissue) Plasma amino acids Protein degradation Glycogenolysis lipogenesis Proteins Ketones Gluconeogenesis Glycerol + Brain Energy Glycogenesis Glycogen Stores (liver, muscle) Protein synthesis Protein Stores (muscle) Ketosis: Ketone bodies (acetoacetate, acetone, beta-hydroxybutyrate) are formed by ketogenesis when liver glycogen is depleted. The substrates are fatty acids and some amino acids 8 ¡ ¡ ¡ ¡ ¡ The brain uses glucose as its sole source of energy except in absolute emergency (ketones). Blood glucose must be maintained within the limits 70 to 120 mg/100 ml. Liver glycogen is the major source of glucose for the brain. When depleted, other sources are used - amino acids can be converted to glucose by gluconeogenesis. Fatty acids (from triglycerides) cannot be used for the brain since they cannot be converted to glucose by gluconeogenesis, but they are used for other tissues to spare brain glucose. 9 ¡ Exocrine functions: 99% of tissue § Enzymes in digestion ¡ Endocrine functions: 1% of tissue - islets § Fuel metabolism § Glucoregulation 10 Endocrine cells – Islets of Langerhans § Highly vascularized, with blood from islets draining into hepatic portal vein. § Pancreatic islet hormones exert major action in the liver prior to entry into the systemic circulation. § Islets are highly innervated by parasympathetic and sympathetic NS – regulate glucose homeostasis during stress 11 Cells and hormones are: Øb (beta) cells (~60%) – insulin Øa (alpha) cells (~30%) – glucagon Ød (delta) cells (~10%) – somatostatin. This is the same molecule as somatastatin in the brain (hypothalamus) that inhibits growth hormone release, but with a different source and function. ØPP cells (also called F cells; 24h), liver glycogen stores are depleted. Glucagon levels rise slightly and insulin declines further. Gluconeogenesis becomes the sole source of hepatic glucose production, using amino acids as a substrate. With starvation, ketones become the primary fuel source (from FAs). 22 ¡ ¡ ¡ ¡ ¡ Ingestion of a carbohydrate load stimulates insulin secretion and suppresses glucagon secretion. Hepatic glucose production and ketogenesis are suppressed. Insulin promotes hepatic glycogen storage. Glucose uptake in muscle is increased, resulting in muscle glycogen synthesis. Fat storage is promoted in adipose tissues. 23 By the end of this lecture you will understand: Intermediary (fuel) metabolism Pancreatic endocrine hormones Insulin Glucagon Other metabolic hormones involved in fuel metabolism 24