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
 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