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

fig 16-6

Green arrows:

stimulated by insulin

Dotted red arrows:

inhibited by insulin

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 lecturesinsulin 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

fig 16-10

Correction:

glycogenolysis in skeletal muscle increases the supply of glucose to the muscle cells, but does not release glucose into the blood

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