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1

3 causes of hyperglycemia

lack of insulin
1. decreased glucose dependent uptake in cells where glucose uptake is insulin-dependent
2. decreased glycogen synthesis
3. increased conversion of amino acids to glucose

2

cause of hyperlipidemia

increased fatty acid mobilization from fat cells
increased fatty acid oxidation (KETOACIDOSIS)

3

cause of ketoacidosis

increased fatty acid oxidation

4

complications of diabetes

cardiovascular - micro and macro angiopathies
neuropathy - increased BG levels lead to increased utilization of the polyol pathway and increased cytosolic water in neural cells
nephropathy - renal vascular changes and changes in the glomerular basement membrane
ocular - cataracts, retinal microaneurysms and hemorrhage
increased susceptibility to infections

5

role of alpha subunits

regulate the insulin receptor
repress the catalytic activity of the beta subunit
repression is relieved by insulin binding

6

insulin effects on liver

inhibits glycogenolysis
inhibits ketogenesis
inhibits gluconeogenesis
stimulates glycogen synthesis
stimulates triglyceride synthesis

7

insulin effects on skeletal muscle

stimulates glucose transport
stimulates AA transport

8

insulin effects of adipose tissue

stimulates TG storage
stimulates glucose transport

9

fasting glucose disposal

75% non-insulin dependent: liver, GI, brain
25% insulin-dependent: skeletal muscle
glucagon secreted to prevent hypoglycemia

10

fed glucose disposal

85% insulin-dependent: skeletal muscle
5% insulin-dependent: adipose tissue
glucagon secretion is inhibited
insulin inhibits release of FFA from adipose tissue

11

GLUT 1

Km 1-2 mM - will pull glucose constantly
constitutive
widely expressed

12

GLUT 2

Km 15-20 mM - requires higher concentrations of glucose to transport
constitutive
B-cells, liver

13

GLUT 3

Km

14

GLUT 4

Km 5 mM - because high enough glucose to require insulin
insulin-induced
skeletal muscle, adipose tissue

15

alpha cells produce...

glucagon: stimulates glycogen breakdown; increases BG

16

delta cells produce...

somatostatin: general inhibitor of secretion of alpha and beta cells

17

beta cells produce...

insulin: stimulates uptake and utilization of glucose
amylin: cosecreted with insulin; slows gastric emptying, decreases food intake; inhibits glucagon secretion

18

proinsulin

cleaved into A and B chains and C (connecting) peptide

19

ultra rapid/very short action insulin

lispro (humalog), aspart (novolog), glulisine (aprida)

20

rapid/short action insulin

regluar

21

intermediate insulin

NPH

22

long acting insulin

glargine (lantus), detemir (levemir) (binds serum albumin extensively)

23

____ leads to covalent modification of proteins

hyperglycemia
loss of normal protein function, acceleration of aging process, theorized to account for may long-term complications of diabetes

24

adverse reactions to insluin

hypoglycemia
lipodystrophy - lump of fat at over used injection site
lipoatrophy - concavities in SC tissue
insulin resistance - immune response to insulin

25

signs of hypoglycemia

weakness, sweating, hunger, tachycardia, increased irritability, tremor, blurred vision, seizures, coma, increased sympathetic output

26

overview of treatment of T1DM and T2DM

T1 - diet + exercise + insulin
T2 - diet + exercise; diet + exercise + oral agents; diet + exercise + insulin

27

T2DM most commonly develops in pts who are

obese and over 35

28

insulin receptor binding stimulates

PDK1: activate protein kinase C to increase amount og glucose transporters to membrane = more glucose uptake
PKB: more glucose transporters; upregulate glycolysis to use glucose
MAPK: cause proliferatin and cell growth to store fatty acids with glycerol

29

drugs that increase BG

catecholamines, GCs, OCs, thyroid hormones, somatotropin

30

drugs that increase risk of hypoglycemia

ethanol, somatostatin, beta-blockers