insulin production, secretion and action

Question 1

Which organ produces insulin?

Answer 1

The pancreas produces insulin.

Question 2

What are the cells of the endocrine pancreas called?

Answer 2

The cells of the endocrine pancreas are called Islet of Langerhan cells

Question 3

What hormone do beta cells produce?

Answer 3

Beta cells produce insulin.

Question 4

What hormone do alpha cells produce?

Answer 4

Alpha cells produce glucagon.

Question 5

What hormone do delta cells produce?

Answer 5

Delta cells produce somatostatin.

Question 6

What hormone do gamma cells produce?

Answer 6

Gamma cells produce pancreatic polypeptide

Question 7

In which specific part of beta cells is insulin synthesised?

Answer 7

Insulin is specifically synthesised in the rough endoplasmic reticulum of pancreatic beta cells.

Question 8

What is insulin cleaved from?

Answer 8

Insulin is cleaved from a precursor called preroninsulin/

Question 9

What is Connecting Peptide?

Answer 9

Connecting Peptide i.e. C Peptide is a by- product of the cleavage of preproinsulin which has no physiological function

Question 10

What is measuring C-Peptide useful for?

Answer 10

By measuring the assay levels of C-Peptide you can determine the levels of insulin being produced by the pancreas.

Question 11

What is the process involved in the secretion of insulin?

Answer 11

1. Glucose enters the beta cells of the pancreas through the GLUT 2 transporter before being phosphorylated by GLUCOKINASE to become glucose-6-phosphate.
2. The glucose-6-phosphate then undergoes glycolysis which results in the production of acetyl-coA which in turn enters the citric acid cycle and produces 36 ATP
3. The ATP produced then binds to the Potassium ATP channel which results in its blockage causing depolarisation of the beta cell membrane.
4. The depolarisation which occurs activates the voltage activated calcium channels which allows calcium to enter the cell membrane
5. The calcium then binds to calcium receptors on insulin vesicles resulting in the exocytosis of insulin.

Question 12

What is important about the Km of glucokinase?

Answer 12

The Km of glucokinase lies within physiological concentrations of glucose levels, this ensures that at very low concentrations of glucose; glucokinase does not convert glucose to glucose-6-phospahte.

Question 13

1 molecular of glucose produces how many ATP?

Answer 13

36 ATP

Question 14

At which point should insulin be realised?

Answer 14

Insulin should only be released during times when blood glucose levels are rising above 5mM

Question 15

The release of insulin is termed?

Answer 15

• The release of insulin is termed bi-phasic.
• This means that 5% of insulin granules are always available for immediate release during the rapid 1st phase of insulin secretion.
• The second phase of insulin secretion depends on the resultant blood glucose levels after the first phase of release

Question 16

type 1 diabetets

Answer 16

type 4 hypersensitivity reaction which destroys beta cells in the islet of langerhans which results in the production of no insulin

Question 17

type 2 diabetes

Answer 17

initially there is hyperinsulinaemia in response to the hyperglycaemia but the insulin receptors in tissue have reduced sensitivity to the insulin (known as insulin resistance) eventually the beta cells may become unable to produce enough insulin to keep up with the hyperglycaemia

Question 18

drugs used in diabetes

Answer 18

sulfonylurea drugs which mimic the action of ATP by blocking the ATP dependant potassium channel resulting in the depolarisation of the cell membrane and the release of insulin

Question 19

when are sulfonylurea drugs used

Answer 19

2nd line for type 2 diabetes and for MODY

Question 20

examples of sulfonylurea drugs

Answer 20

tolbutamide and glibenclamide

Question 21

structure of potassium ATP channels

Answer 21

consists of 2 proteins: Kir6 and SUR1

Question 22

drugs which have the opposite affect of sulfonylurea drugs

Answer 22

diazoxide which stimulates the potassium ATP channels which inhibits the depolarisation of the cell membrane resulting in the inability to release insulin

Question 23

when is diazoxide used

Answer 23

for insulomas of the pancreas which causes hyperinsulinaemia

Question 24

mutations in kir6.2 protein

Answer 24

causes neonatal diabetes resulting in the potassium ATP channel being constantly activated so no cell membrane depolarisation can occur so no insulin can be released , r

Question 25

treatment of neonatal diabetes

Answer 25

sulfonylurea drugs

Question 26

other type of kir6.2 and SUR1 mutations cause

Answer 26

congenital hyperinsulinaemia as the potassium ATP channels is constantly closed and depolarising the cell membrane resulting in insulin release, management is diazoxide

Question 27

MODY stands for

Answer 27

maturity onset diabetes of the young

Question 28

maturity onset diabetes of the young

Answer 28

monogenic diabetes which causes a genetic defect in beta cell function

Question 29

causes of MODY

Answer 29

various causes which can be caused by one of 6 mutations in various genes

Question 30

most common gene mutation in MODY

Answer 30

is a mutation in glucokinase gene means that blood glucose levels must be much higher to produce insulin, i.e. the kM of glucokinase greatly increases

Question 31

other types of MODY involve

Answer 31

HNF transcription factors which play key roles in pancreatic foetal development and also regulates beta cell differentiation and function

Question 32

whys it extremely important to differentiate between MODY and type 1 diabetes

Answer 32

MODY can be managed by sulfonylurea drugs as there is still some function of the beta cells (IE MODY DOES NOT NEED INSULIN)

Question 33

insulin is

Answer 33

a major anabolic hormone in the body

Question 34

insulin increases

Answer 34

• amino acid uptake in muscle
• DNA and protein synthesis
• growth responses
• glucose uptake in muscle and adipose tissue
• lipogenesis in adipose tissue and liver
• glycogen synthesis in the liver and in the muscle

Question 35

insulin switch off

Answer 35

• lipolysis

- gluconeogenesis in the liver

Question 36

insulin signalling

Answer 36

insulin binds to tyrosine kinase receptor which causes the tyrosinase receptor to autophosphorylae which activates the catalytic activity of the receptor

Question 37

insulin resistance

Answer 37

reduced ability of insulin receptors to respond to insulin it is thought to occur through reduced insulin sensing and/or signalling

Question 38

insulin resistance is

Answer 38

most commonly associated with obesity but can also occur when there is near complete absence of adipose tissue, therefore it is assumed that adipose tissue is a key mediator of insulin sensitivity

Question 39

leprechaunism/ donnohue syndrome

Answer 39

rare autosomal genetic trait which causes mutations in the gene for insulin receptors resulting in severe insulin resistance

Question 40

developmental abnormalities in leprechaunish

Answer 40

• elvish facial appearance
• growth retardation
• absence of subcutaneous fat

Question 41

rabson mendenhall syndrome

Answer 41

rare autosomal recessive genetic trait which causes severe insulin resistance, hyperglycaemia and compensatory hyperinsulinaemia

Question 42

developmental abnormalities in raisin mendenhall syndrome

Answer 42

acanthuses nigricans, fasting hypoglycaemia (due to hyperinsulinaemia), diabetic ketoacidosis