Lecture 9 Flashcards Preview

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Flashcards in Lecture 9 Deck (31):
1

Structure of pancreas:

Pancreatic cells are found in clusters called acini. Acini are made up of millions of islets of Langerhans. Each islet has 2500 cells.

2

Secretory products of pancreatic islet cell types:

Alpha: glucagon
Beta: insulin
Delta: somatostatin
F: pancreatic polypeptide

3

Neural innervation of pancreatic islets:

Cholinergic to stimulate insulin secretion.
Alpha adrenergic to inhibit.
Beta adrenergic to stimulate.

4

% of pancreatic islet cell types:

Alpha: 20%
Beta: 70%
Delta: 7%
F: 3%

5

Biosynthesis of insulin:

B cells make mRNA.
Ribosomes synthesize preproinsulin.
ER folds preproinsulin into proinsulin and gives it disulfide bonds.
Trans-Golgi packages proinsulin into secretory granules.
Proteases cleave proinsulin to insulin.

6

Glucose transporters:

GLUT1 - RBCs and endothelial cells
GLUT2 - renal tubular cells, hepatic cells, pancreatic beta cells
GLUT4 - adipose, skeletal muscle, cardiac tissue

7

Regulation of insulin release by beta cell:

Glucose enters via GLUT2. Increased glucose metabolism increases ATP concentration. ATP inhibits out K+ channels. Depolarization activates Ca2+ channel. Increased Ca2+ leads to exocytosis of insulin.

8

Composition of insulin secretion:

5% proinsulin, equimolar C-peptide and insulin.

9

Factors that stimulate insulin release:

Increased glucose, AA, fatty acids, ketoacid.
Glucagon, growth hormone, cortisol, ACh, gastric inhibitory peptide.
Obesity.
Drugs that inhibits ATP-dependent K+ channels.

10

Factors that inhibit insulin release:

Decreased glucose.
Fasting, exercise.
Somatostatin.
Alpha-adrenergic agonists.

11

Insulin response to oral vs IV glucose:

Greater response to oral because of GIP's independent stimulatory effect.

12

What kind of receptor is a insulin receptor? (2)

Catalytic: triggers enzymatic activity on cytoplasmic side when bound.
RTK: phosphorylates tyrosine on itself and others.

13

Insulin receptor structure:

Heterotetramer with two extracellular alpha chains and two membrane-spanning beta chains.

14

Where does insulin bind on insulin receptors?

Cysteine-rich region of alpha chains.

15

Factors determining number of insulin receptors on a cell:

Receptor synthesis
Endocytosis of receptors
Endocytosis by degradation

16

Factors determining insulin's ability to act on a target cell:

Number of receptors
Receptors' insulin affinity
Receptors' ability to transduce insulin signal

17

Mechanisms of insulin signal transmission:

SH2 domain proteins bind and (P)ate tyrosines on insulin receptor on lipids.
Insulin receptor (P)ates and activates other proteins.
Insulin receptor (P)ates insulin-receptor substrates (IRS).

18

IRS: what are they? what they do?

Docking proteins for SH2 domains. Use PIP3 cascade to insert GLUT4 into membrane, and enhance glycogen synthesis. Use MAPK to activate glycogen synthase.

19

IRS: different kinds

1, 2, 3, 4.
IRS-1: skeletal muscle.
IRS-2: hepatic insulin action, supporting pancreatic beta cells.
IRS-3 and 4: redundant.

20

Lipoprotein lipase is a big weirdo:

Breaks down lipids and also enhances reuptake of lipids.

21

Insulin effect in liver: (3)

Promotes glycogenesis.
Promotes lipogenesis.
Promotes protein metabolism.

22

Insulin effect in muscle: (4)

Stimulates uptake of glucose (GLUT4).
Slightly promotes glycogenesis.
Promotes glucose breakdown.
Promotes protein synthesis (skeletal).

23

Insulin effect in adipose tissue: (4)

Stimulates uptake of glucose (GLUT4).
Stimulates glucose breakdown.
Promotes triglyceride formation.
Promotes lipoprotein lipase synthesis.

24

Hypoglycemia: manifestations

Early: Palpitations, tachycardia, diaphoresis, anxiety, hyperventilation, shakiness, weakness, hunger, nausea.
Prolonged/severe: confusion, unusual behaviour, hallucinations, seizures, focal neurologic deficits, coma.

25

Hyperglycemia: manifestations

Early: weakness, polyuria, polydipsia, altered vision, weight loss, mild dehydration.
Prolonged/severe: Kussmaul hyperventilation, stupor, coma, hypotension, cardiac arrhythmias.

26

Glucagon's role during hypoglycemia:

Stimulating glycogenolysis, gluconeogenesis, ketogenesis

27

Glucagon vs insulin:

Glucagon usually antagonizes insulin in the liver.

28

Glucagon signalling pathway:

AC.

29

Effects on glucagon on liver:

Promote glycogen breakdown.
Promote gluconeogenesis.
Promote oxidation of fats.

30

Microvascular diabetic complications:

Retinopathy, nephropathy, neuropathy

31

Macrovascular diabetic complication:

Coronary artery disease/heart disease, stroke, peripheral arterial disease