Endo 3 - Insulin secretion / intermediary metabolism

Question 1

What is T1DM?

Answer 1

Elevated blood glucose due to complete insulin deficiency. Insulin is required to prevent ketoacidosis.

Question 2

What is T2DM?

Answer 2

Elevated blood glucose due to insulin resistance. Insulin is produced, but the receptors are resistant to its actions. It is related to hypertension and dyslipidaemia (part of the metabolic syndrome).

Question 3

What is normal blood glucose range?

Answer 3

4.0-5.5 Mm

Question 4

General diabetes definition

Answer 4

Blood glucose concentration elevation and lack of controlled physiological feedback loop

Question 5

What is special about the brain?

Answer 5

The brain cannot digest lipids. This is because lipolytic enzymes, are not present in the brain; it is suggested that lipolytic enzymes may degrade brain tissue, which has a high proportion of fat.
So glucose is a very important energy substrate especially for the brain

Question 6

State 4 hormones that increase blood glucose concentration

Answer 6

Glucagon
Catecholamines
Somatotrophin
Cortisol

Question 7

What percentage of pancreatic cells are islets of Langerhans?

Answer 7

2%

The other 98% for exocrine secretions - duct to the small intestine

Question 8

What do aplha cells, beta cells and delta cells produce?

Answer 8

Alpha - Glucagon
Beta - Insulin - decrease BG and stimulate growth and development
Delta - somatostatin - inhibits insulin and glucagon via paracrine actions

Question 9

Other than increased BG, which factors influence insulin secretion by beta cells?

Answer 9

Inhibitory: SS, sympathetic nervous activity
Stimulatory: certain aa, certain GI hormones, glucagon released by alpha cells, parasympathetic activity

Question 10

What are the main effects of insulin?

Answer 10

3 main main;
Increased glycogenesis
Increased glycolysis
Increased glucose transport into cells via GLUT 4

Other also important:
Decreased lipolysis, increased lipogenesis
Increased aa transport and protein synthesis

–> results in overall decreased BG

Question 11

What is the effect of GLP-1?

Answer 11

Amplifies our insulin response - it makes us produce more insulin
GLP-1 is secreted in response to nutrient inthe gut

Question 12

What are the main effects of glucagon?

Answer 12

Increased HEPATIC GLYCOGENOLYSIS
Increased blood glucose

Increased amino acid transport into liver which leads to increased GLUCONEOGENESIS thus leading to increased blood glucose
Increased lipolysis leading to increased gluconeogenesis and thus increased blood glucose

Question 13

What affects glucagon secretion?

Answer 13

Decreased Blood glucose leads to Glucagon release 
Other stimulatory molecules: 
Certain GI hormones 
Certain amino acids 
Sympathetic nervous system

Inhibitory molecules:
Beta cells secrete insulin
Parasympathetic nervous activity
Somatostatin

Question 14

What is the role of glucokinase (=hexokinase IV)?

Answer 14

It is the rate limiting step that regulates insulin secretion in beta cells
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 15

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

Answer 15

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 16

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

Answer 16

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 17

What is the incretin effect?

Answer 17

Oral glucose leads to greater insulin releas compared to IV glucose due to the effects of gut hormones (GLP-1)

Question 18

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

Answer 18

Insulin is secreted in a biphasic manner:
First Phase Insulin: Stored insulin, directly released after a meal. In T2DM, the patients lose their first phase insulin.
Second Phase Insulin: Newly-synthesised Insulin released over a couple of hours.

Question 19

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

Answer 19

Two alpha subunits which detect insulin
Beta subunits cross-membrane have tyrosine kinase domains
insulin does not cross membrane

Question 20

Where does the fault causing insulin resistance lie?

Answer 20

recognition of insulin is fine, it’s the transmembrane portion of the receptor that doesn’t work