Lecture 9

Question 1

Structure of pancreas:

Answer 1

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

Question 2

Secretory products of pancreatic islet cell types:

Answer 2

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

Question 3

Neural innervation of pancreatic islets:

Answer 3

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

Question 4

% of pancreatic islet cell types:

Answer 4

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

Question 5

Biosynthesis of insulin:

Answer 5

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.

Question 6

Glucose transporters:

Answer 6

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

Question 7

Regulation of insulin release by beta cell:

Answer 7

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.

Question 8

Composition of insulin secretion:

Answer 8

5% proinsulin, equimolar C-peptide and insulin.

Question 9

Factors that stimulate insulin release:

Answer 9

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

Question 10

Factors that inhibit insulin release:

Answer 10

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

Question 11

Insulin response to oral vs IV glucose:

Answer 11

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

Question 12

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

Answer 12

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

Question 13

Insulin receptor structure:

Answer 13

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

Question 14

Where does insulin bind on insulin receptors?

Answer 14

Cysteine-rich region of alpha chains.

Question 15

Factors determining number of insulin receptors on a cell:

Answer 15

Receptor synthesis
Endocytosis of receptors
Endocytosis by degradation

Question 16

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

Answer 16

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

Question 17

Mechanisms of insulin signal transmission:

Answer 17

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).

Question 18

IRS: what are they? what they do?

Answer 18

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

Question 19

IRS: different kinds

Answer 19

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

Question 20

Lipoprotein lipase is a big weirdo:

Answer 20

Breaks down lipids and also enhances reuptake of lipids.

Question 21

Insulin effect in liver: (3)

Answer 21

Promotes glycogenesis.
Promotes lipogenesis.
Promotes protein metabolism.

Question 22

Insulin effect in muscle: (4)

Answer 22

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

Question 23

Insulin effect in adipose tissue: (4)

Answer 23

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

Question 24

Hypoglycemia: manifestations

Answer 24

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

Question 25

Hyperglycemia: manifestations

Answer 25

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

Question 26

Glucagon’s role during hypoglycemia:

Answer 26

Stimulating glycogenolysis, gluconeogenesis, ketogenesis

Question 27

Glucagon vs insulin:

Answer 27

Glucagon usually antagonizes insulin in the liver.

Question 28

Glucagon signalling pathway:

Answer 28

AC.

Question 29

Effects on glucagon on liver:

Answer 29

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

Question 30

Microvascular diabetic complications:

Answer 30

Retinopathy, nephropathy, neuropathy

Question 31

Macrovascular diabetic complication:

Answer 31

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