7. Insulin

Question 1

What type of hormone is insulin?

Answer 1

Polypeptide

Question 2

Which cells produce insulin?

Answer 2

Beta cells of islet of Langerhans in pancreas

Question 3

What is the primary function of insulin?

Answer 3

Facilitate the uptake of glucose into cells

Question 4

Which organs do not require insulin for glucose uptake?

Answer 4

Brain
Liver
Kidneys

Question 5

What are the functions of somatostatin?

Answer 5

Suppress release of insulin and glucagon
Suppress release of gastrin, CCK
Inhibit the release of GH and TSH

Question 6

What is the function of glucagon?

Answer 6

Raises glucose levels by enhancing gluconeogenesis and glycogenolysis

Question 7

Describe the synthesis of insulin up to proinsulin

Answer 7

mRNA is translated as a single chain precursor, preproinsulin
Signal peptide is removed by endopeptidases in the RER to make proinsulin

Question 8

What are the 3 domains of proinsulin?

Answer 8

Amino-terminal B chain
Carboxy-terminal A chain
Connecting C peptide

Question 9

What is the structure of mature insulin?

Answer 9

51 amino acids

2 unbranched peptide chains linked by 2 disulphides

Question 10

What converts proinsulin into mature insulin?

Answer 10

PC2 and 3

Carboxypeptidase E

Question 11

Describe the events leading up to insulin release

Answer 11

1. Glucose enters through GLUT2
2. Glucose is metabolised via glucokinase
3. ATP is generated
4. ATP-sensitive K+ channels close
5. Depolarisation of cell membrane due to increased intracellular K+
6. Opens voltage-sensitive Ca++ channels, Ca enteres
7. Increased Ca++ triggers release of insulin containing secretory granules

Question 12

What are the causes of hyperinsulinism?

Answer 12

Insulinomas
Congenital
Drug induced
Too much exogenous insulin

Question 13

What are 3 genetic defects that can result in hyperinsulinism?

Answer 13

Katp channel disorders
Glucokinase gain-of-function mutation (beta cell releases insulin at lower glucose levels)
Hyperammonaemic hyperinsulinism

Question 14

What is hyperammonaemic hyperinsulinism?

Answer 14

Gain-of-function mutation of glutamate dehydrogenase
Beta cells secrete insulin in response to an increase in the ATP/ADP ratio caused by AA breakdown and formation of alpha-ketoglutarate
More insulin is secreted

Question 15

What regulates insulin release?

Answer 15

Glucose and amino acids
Glucagon and somatostatin
GIP and GLP

Question 16

Where is glucagon produced?

Answer 16

Pancreatic alpha-cells
Intestinal neuroendocrine L-cells
Brain

Question 17

What stimulates glucagon secretion?

Answer 17

Low blood glucose and low insulin
Rise in amino acids following a protein meal
Adrenaline and noradrenaline

Question 18

What is proglucagon converted to in pancreatic alpha cells?

Answer 18

Glucagon
Glicentin-related pancreatic peptide
MPF

Question 19

What is proglucagon converted to in intestinal neuroendocrine L-cells?

Answer 19

Glucagon-like peptide-1
GLP-2
Glicentin

Question 20

What are the functions of GLP-1?

Answer 20

Stimulates insulin secretion
Stimulates somatostatin release
Inhibits glucagon secretion

Question 21

What are the functions of glicentin?

Answer 21

Stimulates insulin secretion
Inhibits gastric acid secretion
Regulates gut motility

Question 22

What is the short-term function of insulin?

Answer 22

Increased transport of glucose, amino acids and K+ into insulin sensitive cells

Question 23

What are the intermediate functions of insulin?

Answer 23

Stimulate the entry of AAs into cells and protein synthesis
Inhibit protein degradation
Activate glycolysis and glycogen synthesis
Inhibit glycogenolysis and gluconoegenic enzymes

Question 24

What is the delayed function of insulin?

Answer 24

Increase in mRNAs for lipogenic and other enzymes

Question 25

What type of receptor is an insulin receptor?

Answer 25

Tyrosine kinase

Question 26

What domains are in the alpha subunit of an insulin receptor?

Answer 26

Insulin binding domain

Question 27

What domains are in the beta subunit of an insulin receptor?

Answer 27

ATP-binding | Tyrosine kinase

Question 28

What are the events following insulin binding to its receptor?

Answer 28

1. Binding causes autophosphorylation of tyrosines in beta subunits 2. Activated receptor phosphorylates intracellular proteins 3. Activation of signalling pathways

Question 29

How is the insulin receptor regulated?

Answer 29

After binding the receptor is internalised | Insulin is degraded in lysosomes

Question 30

Which glucose transporter is insulin responsive?

Answer 30

GLUT 4

Question 31

Which glucose transporter is used by the liver?

Answer 31

GLUT 2

Question 32

Which glucose transporter is used by the brain?

Answer 32

GLUT 3

Question 33

What is the half life of circulating insulin?

Answer 33

4-6 minutes

Question 34

Besides diabetes mellitus, what are other reasons for hyperglycaemia?

Answer 34

``` Genetic defects of beta function of insulin action Diseases of exocrine pancreas Endocrinopathies Drug/chemical induced Infections ```

Question 35

What are the symptoms of type 1 diabetes mellitus?

Answer 35

``` Polydipsia Polyuria Glycosuria Weight loss with increased appetite Fatigue Nausea Vomiting Diabetic ketoacidosis ```

Question 36

What are the symptoms of type 2 diabetes mellitus?

Answer 36

``` Polydipsia Polyuria Glycosuria Increased appetite Fatigue Blurred vision Slow-healing infections Impotence in men ```

Question 37

What is diabetic ketoacidosis?

Answer 37

Without insulin the body can't use glucose and breaks down fat to use for energy When fats are broken down, ketones are produced in the liver If levels of ketones can't be excreted in urine they build up in the blood, leading to ketoacidosis

Question 38

What are the symptoms of ketoacidosis?

Answer 38

Shortness of breath Breath that smells sweet Nausea, vomiting Dry mouth