Insulin secretion and intermediary metabolism and diabetes Mellitus

Question 1

What 4 factors increase blood Glucose levels?

Answer 1

Glucagon Catecholamines Somatotrophin Cortisol

Question 2

What do delta cells produce?

Answer 2

somatostatin

Question 3

What proportion of the pancreas is associated with exocrine and endocrine function?

Answer 3

98% exocrine 2% endocrine

Question 4

Briefly describe how insulin produced

Answer 4

1. Synthesised from prohormone 2. Signal sequence cleaved off 3. 3 Disulfide bridges formed 4. C chain is cleaved off

Question 5

Where is GLUT 4 mainly found?

Answer 5

muscle and adipose tissue

Question 6

Draw a diagram to show how insulin is produced from beta cells

Answer 6

Question 7

What’s the role of somatostatin?

Answer 7

reduces secretion of insulin and glucagon

Question 8

What does insulin reduce?

Answer 8

• glycogenolysis in muscle + liver
• gluconeogenesis in liver
• breakdown of amino acids in liver
• lipolysis
• production of ketone bodies from NEFA

Question 9

What does insulin increase?

Answer 9

• glycogenesis in muscle + liver
• glycolysis in liver + adipose tissue
• Amino acid uptake + protein synthesis in muscle, liver + adipose tissue
• Lipogenesis and esterification of FA in liver + adipose tissue
• Glucose uptake via GLUT 4, causes 7 fold increase in muscle + adipose tissue

Question 10

What happens during the fasted state?

Answer 10

Question 11

What happens during the fed state?

Answer 11

Question 12

What happens during increased blood glucose?

Answer 12

Question 13

What happens during decreased blood glucose?

Answer 13

Question 14

How do sulphonylureas work?

Answer 14

Close ATP sensitive K + channel hence initiate insulin secretion

Question 15

How is insulin secretion regulated?

Answer 15

Question 16

What is the incretin effect?

Answer 16

• Different insulin response to oral vs IV glucose
• GLP-1 is a gut hormone
• Secreted in response to nutrients in the gut
• Transcription product of proglucagon gene, mostly from L cell
• Stimulates insulin, suppress glucagon
• Increases satiety
• Short half life due to rapid degradation from enzyme dipeptidyl peptidase-4 (DPPG-4)

Question 17

What are the three main ketone bodies?

Answer 17

Acetone
Acetoacetate
3-hydroxybutyrate

Question 18

What is T1DM?

Answer 18

ABSOLUTE insulin deficiency

Question 19

What causes T1DM?

Answer 19

Autoimmune destruction of pancreatic beta cells

Question 20

What does GLP-1 stand for?

Answer 20

Glucagon like peptide -1

Question 21

What are the symptoms of T1DM ?

Answer 21

• Proteolysis with weight loss
• Hyperglycaemia
• osmotic symptoms
• Ketonuria
• Polyuria
• Polydipsia
• Glycosuria

Question 22

What is hypoglycaemia?

Answer 22

plasma glucose <3.6 mmol/l, consciousness is impaired at <2 mmol/l

Question 23

Where does insulin resistance lie?

Answer 23

liver, muscle and adipose tissue

Question 24

What does omental fat/waist circumference indicate?

Answer 24

an individual’s risk of ischaemic heart disease

Question 26

Define ketone bodies

Answer 26

3 water-soluble molecules that are produced by the liver from fatty acids during periods of low food intake or carbohydrate restriction.

Question 27

What are the symptoms of T2DM?

Answer 27

* 60-80% obese * Dyslipidaemia * Later insulin deficiency ( exhaustion of beta cells ) * hyperglycaemia * fewer osmotic symptoms * T2DM presents often with complications

Question 28

What two pathways does insulin have an effect on?

Answer 28

``` Metabolic Pathway (PI3K-Akt) Mitogenic Pathway (MAPK) - increased affect on this pathway ``` compensatory hyperinsulinaemia

Question 29

How can you differentiate between T1DM and T2DM?

Answer 29

REMEMBER: insulin inhibits the conversion of fatty acids to ketone bodies HIGH glucose + HIGH ketone bodies = T1DM Usually, people with T2DM still produce enough insulin to suppress ketone body production though their blood glucose will be high.

Question 30

What diet changes are recommended to someone with T2DM?

Answer 30

Reduce: * fat * refined carbohydrates * sodium Increase: * complex carbohydrates * soluble fibres

Question 32

Why is First Phase Insulin Release (FPIR) important?

Answer 32

Switches off hepatic gluconeogenesis