Lecture 4 - Diabetes & Insulin secretion and intermediary metabolism

Question 1

What are the hormones that induce a reduction of glucose in the blood?

Answer 1

Insulin

Question 2

Which hormones increase blood glucose levels?

Answer 2

Glucagon Catecholamines Somatotrophins Cortisol

Question 3

What is the average value of glucose in the blood?

Answer 3

4-6 mmol/litre

Question 4

What is the definition of T1DM?

Answer 4

Elevated glucose where insulin is required to prevent ketoacidosis

Question 5

What is the definition of T2DM?

Answer 5

In terms of glucose but also related to hypertension and dyslipidaemia (elevated LDLs and decreased HDLs)

Question 6

Which type of DM is more common?

Answer 6

T2

Question 7

What type of diabetes are there?

Answer 7

T1, T2, Maturity onset of diabetes of the Young (MODY)

Question 8

How do we treat diabetes?

Answer 8

Symptomatically, to avoid complications and mortality

Question 9

Treatment for T1DM

Answer 9

Diet is important Insulin can be given physiologically Capillary glucose monitoring - as no physiological feedback loop

Question 10

Hypoglycaemia is caused by..?

Answer 10

An imbalance of diet, exercise and insulin

Question 11

Why is glucose important?

Answer 11

Acts as an energy substrate, especially for CNS (only uses glucose under normal conditions)

Question 12

Definition of hypoglycaemia:

Answer 12

A blood glucose level of less than 4 mmol/litre

Question 13

At what concentration can BGL cause unconciousness, coma and death?

Answer 13

> 2mmol/litre

Question 14

What is most of the pancreas associated with?

Answer 14

Exocrine secretions via ducts

Question 15

What cells are present in the Islets of Langerhans?

Answer 15

Alpha, Beta and Delta cells

Question 16

How are the IoL set out?

Answer 16

3 adjacent cells all have tight junctions - form small intracellular spaces And gap junctions - allowing small molecules to pass between cells

Question 17

What do the alpha cells release?

Answer 17

GLUCAGON

Question 18

What do the beta cells release?

Answer 18

INSULIN

Question 19

What do the delta cells release?

Answer 19

SOMATOSTATIN (all purpose -ve hormone)

Question 20

How does somatostatin influence Growth and Development and BGL?

Answer 20

SS inhibits the release of glucagon and insulin, hence means that growth and development is inhibited and bgl would increase (if insulin inhibited) and bgl would decrease (if glucagon inhibited)

Question 21

How is insulin production regulated by the beta cell’s influences?

Answer 21

Question 22

What is the function of Insulin?

Answer 22

Increases a.a. transport and protein synthesis

Decreases lipolysis Increases lipogenesis

*Increases glycogenesis, glycolysis and glucose transport into cells via GLUT4*

DECREASES BLOOD GLUCOSE

Question 23

How is glucagon release regulated by the alpha cells’s stimulation?

Answer 23

Question 24

What is the function of Glucagon?

Answer 24

Increases lipolysis, a.a. transport into liver

Increased gluconeogenesis and hepatic glycogenolysis

INCREASES BLOOD GLUCOSE

Question 25

What is the mechanism for insulin release?

Answer 25

Glucose enter into cytoplasm via GLUT2 receptor Glucose is phosphorylated via Glucokinase and turned to G6P G6P causes ATP release, closing ATP sensitive K+ channels This causes VGCC to open, causing influx of Ca2+ Ca2+ causes vesicles to move to the membrane surface releasing the insulin out of the beta cell

Question 26

How is insulin synthesised?

Answer 26

Insulin is formed from Proinsulin, which is looks like a C C-peptide insulin is the precursor, and when insulin is formed the C-peptide is cleaved, releasing the A and B chain which forms the insulin molecule

The chains are joined by sulphur bridges

Question 27

What is Glucagon-Like Peptide-1?

Answer 27

Gut hormone which is secreted in response to nutrients in gut Transcription product of proglucagon gene, mostly from L cell Stimulates insulin, inhibits glucagon Increases satiety SHORT HALF LIFE - rapid degradation from dipeptidyl peptidase-4

Question 28

What is the First Phase Insulin Release?

Answer 28

It switches off hepatic output It is a peak at the very beginning, which increases very rapidly and decreases rapidly and then plateaus

Question 29

What kind of energy source is best for diabetics?

Answer 29

Complex carbs are best as it gives them enough time to break it down - 3 hours Diabetics have problems with refined carbs

Question 30

What is the insulin receptor made up of?

Answer 30

It has alpha subunits above the membrane Beta subunits under the membrane The beta subunits have Tyrosine Kinase domains (can auto and cross-phosphorylate) - where phosphorylation of cell protein substrates

Question 31

For glucose to enter RBCs…

Answer 31

No insulin is needed

Question 32

How does T2DM work? - in relation to receptors

Answer 32

The actual receptor is normal in most diabetics The fault is with post-receptor signalling