Glucose Homeostasis

Question 1

What should blood glucose levels be?

Answer 1

4-7 mmol/L
- below 4 —> hypoglycaemia
- below 2 —> coma (possibly fatal)

Question 2

What is the main function of glucose?

Answer 2

Energy substrate

Question 3

When does diabetes mellitus occur?

Answer 3

• leading cause of blindness

Question 4

Which 6 hormones regulate blood glucose?

Answer 4

Increase:
1. Glucagon
2. Cortisol
3. GH
4. Catecholamines

Decrease:
5. Insulin

Inhibit others:
6. Somatostatin

Question 5

What is the prevalence of diabetes mellitus?

Answer 5

7% in UK
- 10% NHS budget

Question 6

What is the structure of the pancreas gland?

Answer 6

Four sections:
1. Head
2. Neck
3. Body
4. Tail

Location:
- retroperitonael —> behind peritoneum

Cells:
- 98% —> exocrine acinar cells
- 2% —> endocrine islets of Langerhans
- α - glucagon
β - insulin
γ - polypeptide
δ - somatostatin

Cell Junctions:
- gap —> small molecules pass between cells
- tight —> small intercellular spaces

Question 7

What is MODY

Answer 7

Maturity Onset Diabetes of the Young
- Monogenetic
- Like genetic T2DM

Question 8

What are the 5 stimulants of insulin secretion?

Answer 8

1. Inc blood glucose —> β cells detect
2. Inc amino acids
3. Some GI hormones
4. Inc glucagon (secreted to prevent hypoglycaemia)
5. PNS activity (+ SNS activity for glucagon)

Question 8

What are the 5 actions of insulin?

Answer 8

1. Inc glycogenesis
2. Inc glycolysis
3. Inc glucose transport via GLUT-4
4. Inc lipogenesis, dec lipolysis
5. Inc amino acid transport —> inc protein synthesis

Question 9

What are the 3 stimulants of glucagon secretion?

Answer 9

1. Dec blood glucose
2. Some amino acids
3. SNS activity (+ PNS activity)

Question 10

What are the 4 actions of glucagon?

Answer 10

1. Inc gluconeogenesis
2. Inc glycogenolysis
3. Inc amino acid transport —> inc gluconeogenesis
4. Inc lipolysis —> inc gluconeogenesis
   - overall: inc HPO

Question 11

How do β cells secrete insulin?

Answer 11

1. Glucose in via GLUT-2 (only insulin-independant
   GLUT)
2. Glucose —> G6P via hexokinase IV (RDS)
3. ATP synthesised —> inhibits K+ channels
4. No K+ in —> depolarisation
5. Stimulates Ca2+ channels —> Ca2+ in
6. Exocytosis of proinsulin vesicles

Question 12

How is insulin obtained from proinsulin?

Answer 12

Proteolytic cleavage:
proinsulin —> insulin + C-peptide

Question 13

Why are C-peptide levels used in diabetes diagnosis?

Answer 13

Produced for pancreatic insulin secretion
- proinsulin —> insulin + C-peptide
- should inc after meal
- T1DM —> low
—> not made when insulin given IV ∵ no
proinsulin
- T2DM —> high

Question 14

What is the incretin effect?

Answer 14

Plasma insulin increases much more with oral glucose than IV glucose
- because of GLP-1

Question 15

What is GLP-1?

Answer 15

Glucagon Like Peptide-1 (gut hormone)
- stimulant —> nutrients in gut
- secreted from L-cells
- effects —> inc insulin
—> dec glucagon
—> inc satiety —> used in obesity + T2DM
treatment (inc weight loss)
- short-half ∵ rapid degradation by dipeptidyl
peptidase-4

Question 16

What is FPIR?

Answer 16

First Phase Insulin Release
- non-diabetic —> high insulin inc immediately after
IV glucose
- diabetic —> little insulin inc after glucose IV glucose

Question 17

How does the insulin receptor work?

Answer 17

Enzymatic receptor
1. Insulin binds to extracellular α-subunits
2. Receptor clusters
3. Conformational change in tyrosine kinase domains
of β-subunit
4. GLUT-4 mobilised