Lecture 13

Question 1

Diabetes

Answer 1

Drinking heaps of H2O and urinating heaps. Massive weight loss. Sweet/organic breath.

Question 2

Insulin secretions

Answer 2

B- cells not able to synthesise insulin. In B cells, the disulfide bonds between certain methionine residues in the chain are cleaved off the pro-insulin to form mature insulin. The connecting peptide may also be detectable in the blood and won’t be present when B-cells stop secreting insulin. C- peptide level in serum indicative of secretion. We use C-peptide as it has a longer half-life than insulin which has varying concentrations between body regions. Diabetics also don’t inject C-peptides therefore, good measure of the difference between insulin therapy and insulin made by the body. Growing pancreatic B cells on a dish to measure insulin secreted into the media around it where first peak is from pre-made insulin that has just been exocytosed and 2nd peak from secretion of newly made insulin.

Question 3

Root cause

Answer 3

Autoimmune attack of the B-cells which is shown in serum by the presence of antibodies. Extent and time-course variable.

Question 4

Symptoms

Answer 4

• thirst
• increase toilet use
• increase tiredness
• weight loss

Question 5

function of insulin

Answer 5

Stimulates lipogenesis, protein synthesis, glycogenesis and prevents glycogen and protein degradation.

Question 6

Glucose uptake

Answer 6

Insulin is needed for GLUT-4 translocation. It helps with glucose transport, lipogenesis, glycogenesis and glycolysis. GLUT-2 are insulin independent while white adipose and muscles are insulin dependent.

Question 7

Protein synthesis and proteolysis

Answer 7

Hypoinsulinemia causes widespread proteolysis and lack of protein synthesis. Excess a.a O2 or converted to glucose/fats.

Question 8

Lipolysis

Answer 8

Insulin inhibits lipolysis. Lack of insulin leads to uncontrolled fat breakdown (lots of fatty acids and glycerol released). It builds glucose when it’s not needed. FAs will inhibit Krebs therefore, no ATP generated.

Question 9

Gluconeogenesis

Answer 9

Insulin inhibits enzymes that cause glucose production in liver. That control is taken away in diabetics. You also have an increase in substrate supply. Lots of glycerol (uncontrolled lipolysis), a.a (uncontrolled proteolysis) and lactate (oxidation of FA inhibit PDH)

Question 10

Ketone bodies

Answer 10

Increase ketone body production due to increase proteolysis. Brain starts to use ketone bodies instead of glucose (major decrease in glucose use)

Question 11

Summary

Answer 11

Uncontrolled release of fatty acids, a.a, glycerol, inhibition of glucose storage and O2 everywhere. Hepatic glucose increases production. Ketone body production increases.

Question 12

Acidosis

Answer 12

Ketone bodies, lactate, FAs are acids causing rapid drop in pH all over body. FATAL

Question 13

Drinking and urinating heaps

Answer 13

Hyperglycaemia changes osmotic strength of blood. Draws H2O out of tissue, simulating thirst.

Question 14

Weight loss

Answer 14

Uncontrolled proteolysis and lipolysis

Question 15

Sugar in urine

Answer 15

Kidneys cannot reabsorb glucose when [glucose]>10nM

Question 16

Sweet/organic breath

Answer 16

Spontaneous decarboxylation of ketone bodies to acetone.

Question 17

Aims of control

Answer 17

1) Avoid prolonged hyperglycaemia
2) Glycerated proteins (damage to capillaries, retina and kidneys)
3) Polyol pathway (accumulation of sorbitol in nerve cells)
4) Avoid catabolic meltdown (ketosis and weight loss)

Question 18

Monitoring

Answer 18

Regular blood glucose readings, looking at glycerated Hb to assess medium term diabetic control (aim for <7.5%)