Glucose Homeostasis

Question 1

Why is glucose so important?

Answer 1

important energy substrate
If the blood glucose concentration falls much below normal levels of 4-5 mmol/L (hypoglycaemia), then cerebral function is increasingly impaired.
If blood glucose concentration <2 mmol/L, unconsciousness, coma and ultimately death can result.

Question 2

How is glucose regulated?

Answer 2

Feedback system

Question 3

What are the 4 hormones involved in regulation?

Answer 3

Glucagon
Cortisol
GH
Catecholamines

Question 4

What does persistent hyperglycaemia result in?

Answer 4

Diabetes Mellitus

Question 5

What % of people are affected with diabetes mellitus in the UK?

Answer 5

7%

Question 6

What is the % risk increase risk of a person with diabetes mellitus dying relative to an age-matched control without diabetes mellitus?

Answer 6

34%

Question 7

How much of the NHS budget is spent on diabetes mellitus?

Answer 7

10%

Question 8

What are the different diabetes mellitus phenotypes?

Answer 8

Type 1
Maturity onset diabetes of the young (MODY)
Type 2

Question 9

What is the structure of the pancreas gland?

Answer 9

Retroperitoneal

Question 10

What is the majority of the pancreas comprised of?

Answer 10

Most of pancreas (98%) generates exocrine secretions via duct to small intestine

Question 11

What is the remaining 2%?

Answer 11

Small clumps of cells within pancreatic tissue (remaining 2%) are called islets of Langerhans

Question 12

What are the three cells of the islets of langerhans?

Answer 12

Alpha- Glucagon
Beta- Insulin
Delta- Somatostatin

Question 13

What are the cell junctions found in the islets of langerhans?

Answer 13

Gap junctions:
Allow small molecules to pass directly between cells
Tight junctions:
Create small intercellular spaces

Question 14

What are the actions of pancreatic hormones?

Answer 14

Insulin stimulates growth and development and reduces blood glucose
Glucagon increases blood glucose

Question 15

What physiological changes occur in response to an increase in plasma concentration?

Answer 15

Beta cells secrete insulin

Question 16

What does insulin cause?

Answer 16

Build up of glycogen stores
Breakdown of glucose
Uptake of glucose
Increase of protein synthesis
Breakdown of fat??

Question 17

What physiological changes occur in response to an decrease in plasma concentration?

Answer 17

Alpha cells secrete glucagon

Question 18

What does glucagon cause?

Answer 18

Increased 
Lipolysis
Gluconeogenesis
Hepatic glycongenolysis
Amino acid transport into liver 
Glucagon increases blood plasma glucose

Question 19

What is glucokinase?

Answer 19

Main glucose sensor

Converts glucose to glucose-6-P in a RDS

Question 20

How is insulin released?

Answer 20

ATP produced from glucose-6-P
Causes release of K+
Causes Ca2+ channels to open
Stimulates release of insulin

Question 21

What is C-peptide?

Answer 21

Used in Insulin assays, as insulin is difficult to measure
Product of cleavage of Proinsulin to form insulin
More stable
Longer half life than insulin
More accurate representation
Not affected by exogenous insulin

Question 22

After a heavy meal what would expect the levels of. C-peptide to be?

Answer 22

High in normal

Low in Type 1 diabetic

Question 23

What is the incretin effect?

Answer 23

The concept that oral glucose administration promotes a much greater degree of insulin secretion compared to a parenteral isoglycemic glucose infusion underlies the incretin effect
Namely the existence of gut-derived factors that enhance glucose-stimulated insulin secretion from the islet β-cell

Question 24

What are the main features of GLP-1?

Answer 24

Gut hormone
Secreted in response to nutrients in gut
Transcription product of pro-glucagon gene, mostly from L-cell

Question 25

What does Glucagon like peptide 1 do?

Answer 25

Stimulates insulin, suppresses glucagon
↑ satiety (feeling of ‘fullness’)
Short half life due to rapid degradation from enzyme dipeptidyl peptidase-4 (DPPG-4 inhibitor)
Used in treatment of diabetes mellitus

Question 26

What is FPIR?

Answer 26

First Phase Insulin Response
Does not occur in Type 2 diabetes
Far more gradual reduction in blood glucose levels

Question 27

What are the main features of the insulin receptor?

Answer 27

Insulin binds to the extracellular domain of the insulin receptor

Once insulin binds to the a-subunit, there is a conformational change in the tyrosine kinase domains of the b-subunits