The endocrine pancreas

Question 1

What type of active transfer does glucose use?

Answer 1

Secondary active transport

Question 2

What glucose transporter is involved with the absorption within the gut?

Answer 2

SGLT1: glucose absorption from gut

Question 3

What glucose transporters are involved with glucose absorption in the kidney?

Answer 3

SGLT1, SGLT2: glucose reabsorption from kidney (PCT)

Question 4

Where is GLUT 1 transporter found and describe its affinity for glucose

Answer 4

GLUT 1 (brain, erythrocytes) – high affinity for glucose: constant uptake of glucose at 2-6 mM

Question 5

Where is GLUT 2 transporter found and describe its affinity for glucose

Answer 5

GLUT 2 (liver, kidney, pancreas, gut) – low affinity: glucose equilibrates across the membrane

Glucose-dependent insulin release in pancreas

Question 6

Where is GLUT 3 transporter found and describe its affinity for glucose

Answer 6

GLUT 3 (brain) – high affinity

Question 7

Where is GLUT 4 transporter found and describe its affinity for glucose?

What recruits these transporters?

Answer 7

GLUT 4 (muscle and adipose tissue) – medium affinity. Insulin recruits transporters

Insulin-dependent uptake of glucose into cells

Question 8

What do alpha cells, beta cells and delta cells in the pancreas secrete?

Are these exocrine or endocrine cells?

Answer 8

α-cells (A cells): glucagon
β-cells (B cells): insulin
δ-cells: somatostatin

Endocrine

Question 9

Describe the arterial and venous drainage of the pancreas

Answer 9

Pancreas supplied by branches of the coeliac, superior mesenteric, and splenic arteries.

The venous drainage of the pancreas is into the portal system.

Question 10

When and where is insulin metabolised?

What is a good index of secretion?

Answer 10

Half of the secreted insulin is metabolized by the liver in it’s first pass; the remainder is diluted in the peripheral circulation

C-peptide is more accurate index of insulin secretion in peripheral circulation (not metabolized by liver)

Question 11

What factors regulate insulin secretion?

Answer 11

1. Plasma glucose
2. AA
3. Glucagon
4. Aloha adregergic (-)
5. PSNS
6. Somatostatin (-)
7. Incretin hormones

Question 12

What factors regulate glucagon secretion?

Answer 12

1. AA
2. Beta-adrenergic
3. PSNS
4. Insulin (-)
5. Somatostatin (-)
6. Plasm glucose (-)

Question 13

How do β cells sense rise in glucose?

Answer 13

Glucose entry to ATP production via glycolysis and TCA. The result is closure of a special kind of K channel, which is ATP-gated (negatively) and consequent membrane depolarization. This in turn leads to increased Ca entry, and intracellular Ca is the signal that triggers insulin exocytosis. If true, it follows that anything that can depolarize the B cell, or otherwise raise intracellular Ca, will also lead to insulin release

Question 14

What type of receptor is insulin and what happens when it binds?

Answer 14

tyrosine kinase

Insulin binds to its receptor (1), which, in turn, starts many protein activation cascades (2). These include translocation of Glut-4 transporter to the plasma membrane and influx of glucose (3), glycogen synthesis (4), glycolysis (5), and fatty acid synthesis (6) (http://en.wikipedia.org/wiki/Insulin_receptor).

Question 15

What happens when glucagon binds to its receptor?

Answer 15

On image

Question 16

How to counter-regulatory hormones mainly act?

Answer 16

Counter-regulatory hormones act principally (not exclusively) through activity of PKA, which phosphorylates key enzymes in metabolic pathways

Insulin action leads to dephosphorylation of these same enzymes

Question 17

How is hyperglycemia central for DM diagnosis?

Answer 17

Random plasma glucose ≥ 11.1 mmol L-1
Fasting plasma glucose ≥ 7.0 mmol L-1
Oral glucose tolerance test (OGT) ≥ 11.1 mmol L-1

Question 18

The incretin effect

Answer 18

They are released in response to food ingestion, they can the release of insulin in beta cells in response to glucose. Causes increased glucose uptake and decreased glucose liver production