Insulin storage, synthesis and function

Question 1

In the islets of Langerhans, what are the 4 major cell types and the hormones they secrete?

Answer 1

• α cells (20% of the islet)  Glucagon
• β cells (65% of the islet)  insulin + amylin
• δ cells (10% of the islet)  somatostatin.
• F cells (1-2%) + other  pancreatic polypeptide or other

Question 2

The central core of the pancreatic islets are made up of ?cells and the outer rim is made up of the ? cells.

Answer 2

beta, alpha

Question 3

Which cells are responsible for the regulation of glucose metabolism?

Answer 3

Alpha and beta

Question 4

Describe the biosynthesis of insulin.

Answer 4

1. Insulin mRNA
2. Pre-proinsulin (hydrophobic) ( manufactured in RER (ribosomes of rER)
3. Transfer to the Golgi
4. Enzymatic cleavage
5. pro-insulin molecule Packaged into secretory granules
6. Maturation
7. Storage in cytosol
8. Secretion | split of connecting (C)-peptide, releasing insulin molecule

Question 5

Equimolar amounts of what are released into the circulation when insulin is secreted?

Answer 5

Insulin and C peptide.

Question 6

What are the two pathways of insulin secretion?

Answer 6

Regulated pathway (most of the insulin is secreted via secretory granules) and constitutive pathway (directly from the granule to the circulation.

Question 7

Pro-insulin molecule includes what two parts?

Answer 7

C peptide and insulin

Question 8

An insulin molecule contains an a chain and a b chain, connected by what type of bonds?

Answer 8

Disulphide

Question 9

What stimulates the secretion of insulin? x6

Answer 9

• Increased blood glucose
• Increased blood free fatty acids
• Increased blood amino acids
• GI hormones (gastrin, secretin etc)
• Glucagon, growth hormone, cortisol
• Parasympathetic stimulation, acetylcholine
• β-Adrenergic stimulation
• Obesity

Question 10

Describe the steps of insulin secretion.

Answer 10

1. Transport of glucose into the β cell through GLUT 2
2. Metabolism of glucose inside the β cell to ATP
3. ATP closes ATP-sensitive K + channels, which depolarizes the β cell membrane.
4. Opening of voltage-sensitive Ca 2+ channels, allowing Ca2+ to move into the cell.
5. Insulin secretion (exocytosis of the insulin-containing secretory granules)

Question 11

What inhibits insulin secretion?

Answer 11

• Decreased blood glucose
• Fasting
• Somatostatin (pancreatic secretion)
• α-Adrenergic agonist (adrenaline and noradrenaline)
• Leptin

Question 12

Describe the structure of an insulin receptor.

Answer 12

Dimer (x2 tyrosine kinase molecules, each with a beta subunit) w/ two alpha sub units to form the insulin binding sites. Alpha subunits connected by disulphide bonds.

Question 13

How is Tyrosine kinase activated in an insulin receptor?

Answer 13

Binding of insulin causes beta subunit to auto-phosphorylate that activates TK.

Question 14

Describe the steps of insulin receptor signaling, beginning with insulin binding to the receptors.

Answer 14

1. insulin binds to the receptor
2. Insulin receptor substrate (IRS) is phosphorylated by tyrosine kinase
3. IRS associates with IP3
4. IP3 stimulates AKT (protein kinase B)
5. AKT phosphorylates AS160
6. Phosphorylation of AS160 leads to the translocation of GLUT 4 from storage vesicles to the cell surface.
7. Glucose then transported into cell

Question 15

Apart from glucose transport, what else does the Insulin receptor substrate (IRS) facilitate?

Answer 15

Protein synthesis
Fat synthesis
Glycogen synthesis
Growth and gene expression

Question 16

What is the action of insulin in the liver?

Answer 16

• stimulates glycolysis and glycogen synthesis, synthesis of long-chain fatty acids and lipogenesis
• Suppresses gluconeogenesis

Question 17

What is the action of insulin in the Adipose tissue?

Answer 17

Increased uptake of fatty acids and glycerol and formation of triacylglycerol

Question 18

What is the action of insulin in the Muscle?

Answer 18

• Stimulates glucose transport, glucose metabolism, glycogen synthesis, and uptake of amino acids and protein synthesis.

Question 19

What tissue is the main target tissue for insulin in a fasting state?

Answer 19

Liver

Question 20

What tissue is the main target tissue for insulin after a meal?

Answer 20

Muscle and adipose

Question 21

In a fasting state, what is insulin’s effect on gluconeogensis?Wrong process?

Answer 21

It is inhibited.

Question 22

Is glucose hydrophobic or hydrophilic?

Answer 22

Hydrophilic

Question 23

Which GLUT is almost universal for all tissues?

Answer 23

GLUT 1

Question 24

Which GLUTs are responsible for intestinal absorption of glucose?

Answer 24

GLUT 2 & 5

Question 25

Which GLUT is responsible for glucose uptake in the brain?

Answer 25

GLUT 1 + 3

Question 26

Which GLUT is responsible for glucose uptake in the adipose tissue and muscle?

Answer 26

GLUT 4

Question 27

Which GLUT is insulin-sensitive?

Answer 27

GLUT 4

Question 28

Which GLUT is responsible for glucose uptake in the testis?correct this

Answer 28

GLUT 14

Question 29

What happens to glucose once it enters the cell?

Answer 29

It undergoes glycolysis and enters the mitochondria to undergo the Krebb’s cycle.

Question 30

Which tissues undergo insulin- mediated glucose uptake and which GLUT is utilised?

Answer 30

Muscle and adipose
GLUT 4

Question 31

What molecule has the opposite effect of insulin?

Answer 31

glucagon

Question 32

Describe the transport of glucose across the BBB.

Answer 32

GLUT 1 facilitates uptake of glucose from capillaries in the brain into associated astrocytes. The astrocyte then transfers clucose to the nerve cell via a GLUT 1 on the astrocyte side and a GLUT 3 on the nerve cell side.

Question 33

What form of insulin has 3 x the half-life of insulin?

Answer 33

Proinsulin

Question 34

What is the significance of cysteine residues and insulin?

Answer 34

contains a third disulphide bond on the alpha chain of insulin.