Glucose homeostasis

Question 1

What is the importance of glucose?

Answer 1

Glucose in an important energy substrate
If blood glucose levels fall below normal levels (4-5mmol/L) then cerebral function is increasingly impaired
If blood glucose falls under 2mmol/L; unconsciousness, coma and ultimately death

Question 2

How is glucose concentration regulated?

Answer 2

When there’s high glucose conc. , insulin is secreted

When there low glucose conc. glucagon, cortisol, GH and catecholamines are secreted

Question 3

What is the most prevalent from of diabetes?

Answer 3

T2DM
then T1DM
Then MODY (maturity onset diabetes of the young)

Question 4

What does persistent hyperglycaemia lead to?

Answer 4

Diabetes mellitus

Question 5

What is important about the pancreas?

Answer 5

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

Remaining 2% are islets of langerhans- endocrine secretion

Question 6

What cells make up the islets of langerhans and what do they secret?

Answer 6

Alpha cells: glucagon
Beta cells: Insulin
Delta cells: Soatostatin

Question 7

What kind of junctions can be found in the islets of langerhans?

Answer 7

Gap junctions: allow small molecules to pass directly between cells
Tight junctions: create small intracellular spaces

Question 8

What is the action of pancreatic hormones?

Answer 8

Glucagon: increase glucose
Insulin: decrease glucose
Somatostatin: regulates insulin and glucose (inhibits then via paracrine action)

Question 9

What is the effect of insulin?

Answer 9

Promotes glycogenesis
Breaks down glucose 
Uptake of glucose
Increases proteogenesis 
Decreases lipolysis

Question 10

How does glucagon increase blood glucose conc.?

Answer 10

Increases amino acid transport into liver for gluconeogenesis
Increases hepatic glucose output
Increases hepatic glycogenolysis
Increases lipolysis

Question 11

What is glucokinase?

Answer 11

GLUT-2 is not insulin sensitive

Glucokinase (hexokinase IV) is thought to be the main glucose sensor

Question 12

How is insulin synthesised?

Answer 12

1. GLUT-2 transports. glucose into beta cells
2. Glucokinase converts glucose to glucose-6- phosphate- rate limiting step
3. G6P leads to ATP production via metabolic pathways
4. ATP- sensitive K+ channel is blocked by ATP
5. Increase in intracellular K+ so depolarisation
6. Opening of VGCC and influx of Ca2+
7. Ca2+ causes insulin vesicles to fuse with cell membrane and causes release of insulin

Question 13

What can pro-insulin be cleaved to?

Answer 13

Can be cleaved to from c-peptide and insulin so there a 1:1 ratio
Insulin is hard to measure in blood so c-peptide is measures

Question 14

What is GLP-1?

Answer 14

Glucagon like peptide-1
Its a gut hormone secreted in response to nutrients in gut
Its a transcription product of pro-glucagon gene, mostly from L-cell
Has a short half-life due to rapid degredation by dipeptyl peptidase-4

Question 15

What is the role of GLP-1?

Answer 15

Stimulates insulin, surpasses glucagon 
Increases satiety (Feeling full)

Question 16

What is first phase insulin release?

Answer 16

Insulin stored in pancreas is released immediately after a meal
Effect lasts for 10-15 mins
People with T2DM don’t have this response

Question 17

What does insulin bind to?

Answer 17

Insulin binds to the extracellular domain of the insulin receptor (alpha subunit)
Once insulin binds to the alpha subunit theres a conformational change in tyrosine kinase domains of the beta subunit

Question 18

How is the insulin receptor structured?

Answer 18

Has 2 alpha and 2 beta subunits

Its tyrosine kinase linked- enzyme linked receptor

Question 19

What is the incretin effect?

Answer 19

Increase stimulation of insulin release after oral digestion of glucose by gut hormones