Insulin Secretion and Intermediary Metabolism

Question 1

State four hormones that increase blood glucose concentration.

Answer 1

Glucagon
Cortisol
Catecholamines
Somatotrophin

Question 2

What is T1DM and T2DM?

Answer 2

T1DM: defined as elevated glucose where insulin is required to prevent ketoacidosis
T2DM is more common and is a considerable health burden. It is defined in terms of glucose but is also related to hypertension and dyslipidaemia (lots of lipids in the blood)

Question 3

State some complications of diabetes.

Answer 3

Diabetic retinopathy
Diabetic ketoacidosis 
Peripheral neuropathy 
Coma 
Heart Attacks 
Stroke

Question 4

What is the normal blood glucose range?

Answer 4

4.0-5.5 mM

Question 5

What percentage of pancreatic cells are islets of Langerhans?

Answer 5

2%

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 (the breakdown of glucose by enzymes)
Increase glucose transport via GLUT-4
Decrease lipolysis and increase lipogenesis
Increased protein synthesis, also prevents breakdown of protein
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 (glucagon-like peptide 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 and increased amino acid transport into liver
Increased gluconeogenesis
Increased hepatic glycogenolysis
Increase blood glucose
INSULIN inhibits glucagon release (via paracrine)

Question 12

What is the role of glucokinase (hexokinase IV)?

Answer 12

It is the rate determining step that regulates insulin secretion

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 pre-proinsulin 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 Intravenous glucose load
This is to do with intestinal hormones

Question 16

What enzyme breaks down GLP-1 (Glucagon-like peptide-1) and where is it found, what does it respond to?

Answer 16

Gut hormone.

• Secreted in response to nutrients in the gut.
• transcription product of the proglucagon gene
• stimulates insulin and suppresses glucagon.
• • Increases satiety (feeling of fullness)
• Dipeptidyl Peptidase-4 (DPPG-4) break down this enzyme rapidly, giving short half life

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

What can DPPG-4 inhibitors be used for?

Answer 20

Treating Type 2 DM