Insulin Secretion and Intermediary Metabolism

Question 1

State four hormones that increase blood glucose concentration.

Answer 1

Glucagon Cortisol Catecholamines Somatotrophin

Question 2

State some complications of diabetes.

Answer 2

Diabetic retinopathy Diabetic ketoacidosis Peripheral neuropathy Coma Heart Attacks Stroke

Question 3

What is the normal blood glucose range?

Answer 3

4.0-5.5 Mm

Question 4

What percentage of pancreatic cells are islets of Langerhans?

Answer 4

2%

Question 5

What do the delta cells in the islets of Langerhans produce?

Answer 5

Somatostatin

Question 6

Why do cells in the islets of Langerhans have gap junctions?

Answer 6

Allow hormones to have a paracrine effect

Question 7

What effect does somatostatin have on glucagon and insulin secretion?

Answer 7

Decreases both insulin and glucagon secretion (it is sometimes called ‘endocrine cyanide’)

Question 8

What are the main effects of insulin?

Answer 8

Increase glycogenesis Increase glycolysis Increase glucose transport via GLUT-4 Decrease lipolysis Increased protein synthesis ( and AA transport) Overall decrease blood glucose

Question 9

State some factors that increase and decrease insulin secretion.

Answer 9

Increase: Certain amino acids Gastrointestinal hormones Parasympathetic activity Decrease: Sympathetic activity Somatostatin

Question 10

What is the effect of GLP-1?

Answer 10

Amplifies our insulin response - it makes us produce more insulin

Question 11

What are the main effects of glucagon?

Answer 11

Increased lipolysis Increased AA transport x Increased hepatic gluconeogenesis Increase blood glucose INSULIN inhibits glucagon release (via paracrine)

Question 12

What is the role of glucokinase?

Answer 12

It is the rate limiting step that regulates insulin secretion It converts glucose to G6P Glucose moves into the beta cell via Glut-2 (which is NOT insulin regulated) It is then converted to G6P by glucokinase (hexokinase IV), which then determines insulin secretion

Question 13

Describe the structure of insulin and what can be measured to indirectly give an indication of blood insulin concentration?

Answer 13

Insulin is synthesised as a prohormone with an A, B and C chains The C chain is removed in the conversion of proinsulin to insulin so the ratio of insulin: C peptide is 1:1 This means that C peptide can be measured to give an indication of insulin output

Question 14

Describe how glucose uptake causes release of insulin from the beta cell.

Answer 14

Glucose enters through Glut-2 and is metabolised to produce ATP There is an increase in intracellular ATP concentration This BLOCKS ATP sensitive potassium channels —> changes membrane potential Leads to opening of voltage dependent Ca2+ channels Ca2+ influx causes insulin exocytosis

Question 15

What is the incretin effect?

Answer 15

Oral glucose load stimulates more insulin release than IV glucose load This is to do with intestinal hormones

Question 16

What enzyme breaks down GLP-1?

Answer 16

Dipeptidyl Peptidase-4 (DPPG-4)

Question 17

Describe the differences in first phase insulin release between a normal person and someone with T2DM.

Answer 17

Administration of glucose causes a sharp increase in insulin in a normal person This surge of insulin (first phase release) is not present in someone with T2DM

Question 18

Describe the structure of the insulin receptor and how it works.

Answer 18

Insulin is a peptide hormone so it doesn’t enter the cell The receptor has two alpha subunits and two transmembrane beta subunits, which have tyrosine kinase domains Insulin binds to the alpha subunits and cause a conformational change in the beta subunits You get phosphorylation of the receptors which recruit other substances that also get phosphorylated and have effects on the metabolic pathway

Question 19

Where does the fault causing insulin resistance lie?

Answer 19

Insulin resistance lies in the post-receptor cytoplasmic elements of insulin function

Question 20

How low would blood glucose need to be to lead to a coma, death and unconsciousness?

Answer 20

2mM

Question 21

What proportion of the pancreas is associated with exocrine secretion?

Answer 21

98%

Question 22

What’s the role of tight junctions in the islet of langerhans?

Answer 22

Form small intracellular spaces. Small collections of fluid between cells are formed by tight junctions.

Question 23

Why is it important that some gastrointestinal hormones increase insulin secretion?

Answer 23

before food we eat effects blood glucose, the food in our gut is making us produce insulin

Question 24

Wheres the main effects of glucagon?

Answer 24

liver - hepatocytes

Question 25

What is pre-proinsulin?

Answer 25

proinsulin plus a signal sequence

Question 26

Whats the other role of the insulin receptor?

Answer 26

growth (mitogenic pathway)

Question 27

Why is First Phase Insulin Release (FPIR) important?

Answer 27

Switches off hepatic gluconeogenesis