Pancreatic Hormones

Question 1

Insulin & Glucagon are synthesized as large ________.

Answer 1

preprohormones

Question 2

Connecting (C) peptide

Answer 2

• aka disulfide bridges
• connects the 2 peptide chains of insulin
• in the case of the beta cells, inuslin & connecting (C) peptide are released into the circulating blood in equimolar amounts
• can be measured with a radioimmunoassay & is a measure of beta cell function in diabetic patients treated with insulin.

Question 3

In the case of the beta cells, _______ & ________ ________ are released into the circulating blood in ________ amounts.

Answer 3

insulin, connecting (C) peptide, equimolar.

Question 4

Insulin is a polypeptide…

Answer 4

containing 2 amino acid chains (21 & 30 a.a) connected by disulfide bridges.
- polypeptide chains = A & B

Question 5

GLucagon is a…

Answer 5

straight-chain polypeptide of 29 amino acid residues.

Question 6

Insulin & glucagon circulate…

Answer 6

unbound to carrier proteins

Question 7

Insulin & glucagon - short half-lives of…

Answer 7

5 - 10 mins

Question 8

Insulin has actions on carbohydrate, fat, & protein metabolism that occurs within seconds, minutes & hours.

Answer 8

A. Rapid = increased:
- glucose,
- amino acid,
- & potassium uptake into cells.

B. Intermediate
- stimulation of protein synthesis
- inhibition of protein degradation
- activation & inactivation of enzymes

C. Delayed
- increased transcription

Question 9

The insulin receptor is a ______ made up of ___ ____ subunits that lie outside the cell membrane & ___ ______ subunits that penetrate the cell membrane & protrude into the cytoplasm.

Answer 9

tetramer, 2 alpha, 2 beta.

Question 10

Metabolic effect of Insulin

Answer 10

The binding of insulin to the alpha subunit of the receptor triggers tyrosine kinase activity of the beta subunits, producing autophosphorylation of the beta subunits on tyrosine residues.
This results in the phosphorylation of other intracellular proteins & enzymes, which mediates a multitude of responses.

Question 11

Glucose transporters

Answer 11

A large family of structurally related transport proteins

Question 12

2 main types of Glucose Transporters

Answer 12

1. Sodium-glucose linked transporters (SGLTs)
2. Facilitated diffusion glucose transporters (GLUTs)

Question 13

Transporters differ in terms of…

Answer 13

their substrate specificity, distribution & regulatory mechanisms.

Question 14

The primary regulatory mechanism by which glucose uptake takes place is…

Answer 14

via insulin-stimulated transport of glucose into skeletal muscle & adipose tissue, primarily mediated by glucose transporter protein type-4 (GLUT4)

Question 15

CLASS 1 =

Answer 15

GLUT 1 - 4

Question 16

CLASS 2 =

Answer 16

GLUT 5 - 11

Question 17

CLASS 3 =

Answer 17

GLUT 6 - 13

Question 18

The function of glucose sensing has 2 components:

Answer 18

1. Entry of glucose into the cell mediated by GLUTs
2. Metabolism of glucose through phosphorylation by glucokinase

Question 19

GLUT 1

Answer 19

• expressed mainly on human beta cells
• in hepatocytes, GLUT1 is associated with the bidirectional transport of glucose controlled by hormones such as thyroid hormone.

Question 20

GLUT 2

Answer 20

• expressed mainly in beta cells of the pancreas, liver & kidney.
• acts as a glucose sensor in the beta cells of marine organisms.

Question 21

In vitro animal & clinical studies have shown that…

Answer 21

the primary pancreatic beta cell sensor is glucokinase & not GLUT1 or GLUT2.

Question 22

GLUT 3

Answer 22

• mainly present in the brain
• has a high infinity for glucose, a property which is consistent with its function to transfer glucose into cells having a higher requirement of glucose.

Question 23

GLUT 4

Answer 23

• is an insulin-responsive glucose transporter that is found in the heart, skeletal muscle, adipose tissue, & brain. (Primarily in skeletal muscle & adipose tissue)
• present in the cytoplasm of cells in vesicles from which it is translocated to the plasma membrane under the influence of insulin.

Question 24

Insulin
- plasma half-life
- clearance from the circulation

Answer 24

Plasma 1/2 life = approx. 5 - 10mins
Clearance = within 10 - 15mins

Question 25

Insulin is degraded by the enzyme?

Answer 25

Insulinase mainly in the liver

Question 26

4 effects of insulin on the liver

Answer 26

1. Increases the flux of glucose into cells = by inducing glucokinase which increases the phosphorylation of glucose to glucose-6-phosphate (readily utilized for the synthesis & storage of glycogen).
2. Increases glycogen synthesis = by activating glycogen synthase & increasing glucose uptake.
3. Directs the flow of glucose through glycolysis = by increasing the activity of key glycolytic enzymes.
4. Decreases the hepatic output of glucose