Absorptive (fed) state

1. Absorptive (fed) state Definition: the few hours after a meal, an anabolic state Carbohydrate: glucose to liver, fat & muscle; main energy source in absorptive state forms glycogen (muscle, liver), triglyceride (adipose, liver) Protein: aminoacids to liver ( ketoacids & urea), to muscle ( protein) Triglyceride: chylomicrons to adipose (storage) liver triglyceride  VLDL to adipose (storage)

2. Absorptive (fed) state fig 16-1

3. Postabsorptive (fasted) state Definition: dependent on stored substrate, a catabolic state Carbohydrate: maintenance of blood glucose level critical (brain metabolism) glucose sources: liver glycogen, gluconeogenesis from protein Protein: muscle aminoacids to liver (gluconeogenesis  glucose) Triglyceride: fatty acids main energy source for skeletal muscle & heart fatty acids  ketone bodies (acetoacetate,  OH butyrate) in liver

4. Postabsorptive (fasted) state fig 16-2

5. Insulin, source, structure & release Source:  cells of Islets of Langerhans in pancreas (endocrine pancreas) Structure: 51 aminoacid peptide, 2 chains joined by -S-S- bonds Release stimulated by:  blood glucose concentration (most important)  aminoacid concentration,  GIP (glucose insulinotropic peptide)  parasympathetic NS activity,  sympathetic NS activity

6. Insulin actions fig 16-4 Insulin acts on skeletal & cardiac muscle, fat, & liver Insulin is anabolic (synthesis of glycogen, protein, triglyceride)

7. Insulin actions Green arrows: stimulated by insulin Dotted red arrows: inhibited by insulin fig 16-6

8. Regulation of blood glucose by insulin fig 16-7

9. Mechanism of action of insulin on glucose transport fig 16-5 Reminder: from our signal transduction lectures insulin receptor phosphorylates itself (chap 5 slide 6) similar to mechanism of ADH on renal collecting duct

10. Diabetes mellitus Type I diabetes mellitus: (~10% patients) no insulin is secreted by Islets of Langerhans autoimmune disease, destruction of  cells must be treated by insulin injections Type II diabetes mellitus: (~90% patients) insulin normal or even elevated, tissues resistant to insulin associated with weight gain, middle age but increasing in young treated with insulin or drugs which increase tissue sensitivity to insulin, weight reduction, exercise some genetic link

11. Pathology of type I diabetes mellitus Overview:  plasma [glucose] but  intracellular [glucose]  plasma FA’s  fatty acid metabolism but no Kreb’s intermediates for oxidative phosphorylation FA’s metabolized to acetyl CoA then  ketoacids (ketosis) ketone bodies (acetoacetate,  OH butyrate)  acidosis osmotic diuresis ( filtered glucose)  dehydration Mechanisms: decreased plasma insulin  glucose uptake by muscle, adipose tissue, liver  glycogenolysis by liver  glucose release  triglyceride synthesis (adipose tissue)  fatty acid release  glucose (adipose tissue)   glycerophosphate  TG synthesis  gluconeogenesis from glycerol & AA’s  protein breakdown in muscle

12. Pathology of type I diabetes mellitus fig 16-12

13. Glucagon Source:  cells of Islets of Langerhans in pancreas (endocrine pancreas) Structure: 31 aminoacid peptide Release stimulated by:  blood glucose concentration (most important)  sympathetic NS activity Actions: note-glucagon works on liver & is catabolic  breakdown of liver glycogen  blood glucose  gluconeogenesis (liver)  blood glucose  ketone synthesis (liver)  ketosis

14. Glucagon glucose interplay fig 16-9

15. Sympathetic NS & epinephrine General principles: SNS activity & epinephrine release stimulated by  blood [glucose] SNS/epi is catabolic, acting on liver, adipose tissue, skeletal muscle these actions help mobilize metabolic resources Actions:  glycogen breakdown (skeletal muscle), not glucose release  glycogenolysis (liver)  blood [glucose]  gluconeogenesis (liver)  blood [glucose]  lipolysis (adipose tissue)  blood [fatty acid] &  blood [glycerol]

16. Sympathetic NS & epinephrine Correction: glycogenolysis in skeletal muscle increases the supply of glucose to the muscle cells, but does not release glucose into the blood fig 16-10

17. Cholesterol Source: diet (variable amount absorbed from intestine) synthesis (most cells,  liver,  endocrine cells) Functions: normal component of lipid phase of cell membranes synthesis of steroid hormones aldosterone, cortisol (adrenal cortex) testosterone, estrogen, progesterone (gonads, placenta) synthesis of bile salts (liver) Pathological effects: incorporated into macrophages & smooth muscle cells  foam cells foam cells important components of atherosclerotic plaques

18. Cholesterol Regulation of plasma cholesterol:  dietary cholesterol  plasma cholesterol  liver synthesis & vice versa, hence plasma cholesterol not very responsive to diet Drugs can  synthesis, or  GI absorption fig 16-13

19. Movement of cholesterol around body VLDL (very low density lipoproteins) made in liver, mostly TG, TG taken up by adipose tissue LDL (low density lipoproteins) made from VLDL after TG goes to adipose tissue cholesterol delivered to tissues (& atherosclerotic plaques) “bad” cholesterol HDL (high density lipoproteins) made in liver & GI tract removes excess cholesterol from blood & cells delivers cholesterol to endocrine cells & excretion by liver “good” cholesterol