4 - Insulin Secretion

Question 1

What is the structure of insulin and what can be measured to indirectly give an indication of blood insulin concentration?

Answer 1

• synthesised as prohormone with A, B and C chains
• C chain removed in conversion of proinsulin to insulin
• ratio of insulin: C peptide is 1:1
• C peptide measured to give indication of insulin output

Question 2

What is the incretin effect?

Answer 2

• oral glucose load stimulates more insulin release than IV glucose load
• to do with intestinal hormones

Question 3

What hormone decreases blood glucose?

Answer 3

insulin

Question 4

What hormones increases blood glucose?

Answer 4

• glucagon
• catecholamines
• somatotrophin
• cortisol

Question 5

What are the 3 cell types in pancreatic islets of Langerhans and what do they secrete?

Answer 5

• α cells: glucagon
• β cells: insulin
• δ cells: somatostatin

Question 6

What does somatostatin do?

Answer 6

decreases production of insulin and glucagon

Question 7

What are some features of the islets of langerhans?

Answer 7

• small clumps of cells
• 2% of cells in pancreas (not associated with exocrine secretions via duct into small intestine)
• gap junctions between cells allow small molecules to pass directly between cells (paracrine effect)
• tight junctions form intercellular spaces (collections of fluid between cells)

Question 8

What factors increase insulin secretion?

Answer 8

• increased blood glucose
• glucagon
• parasympathetic activity (β receptors)
• some GI hormones
• glucagon like peptide
• certain amino acids

Question 9

What factors decrease insulin secretion?

Answer 9

• somatostatin

- sympathetic activity (α receptors)

Question 10

What can the brain use as an energy supply?

Answer 10

• ketones
• glucose
• NOT fatty acids

Question 11

What are the physiological actions of insulin?

Answer 11

• decreases blood glucose conc. (increases glycogenesis, glycolysis and glucose transport into cell using GLUT-4)
• prevents breakdown of protein
• stops lipolysis
• increases lipogenesis

Question 12

What factors increase glucagon secretion?

Answer 12

• decreased blood glucose
• certain amino acids
• certain GI hormones
• parasympathetic activity
• sympathetic activity

Question 13

What factors decrease glucagon secretion?

Answer 13

• insulin

- somatostatin

Question 14

What are the physiological actions of glucagon?

Answer 14

• increases hepatic glycogenolysis (increasing blood glucose)
• increases lipolysis, increasing gluconeogenesis (increasing blood glucose)
• increases amino acid transport to liver, increasing gluconeogenesis (increasing blood glucose)

Question 15

How is insulin secreted?

Answer 15

• glucokinase is rate determining step regulating secretion
• glucose enters cell through GLUT-2 (not insulin regulated)
• glucose converted to glucose-6-phosphate by glucokinase (important for sensing glucose conc. by β cell)
• ATP produced blocks ATP sensitive potassium channels
• VGCC open, allowing calcium to rush in and insulin to be secreted

Question 16

What are the 2 types of diabetes mellitus and what are their defining features?

Answer 16

• type 1: elevated glucose where insulin is required to prevent ketoacidosis
• type 2: defined in terms of glucose but related to hypertension and dislipidaemia

Question 17

What is glucagon like peptide 1 (GLP-1) and its features?

Answer 17

• gut hormone secreted in response to nutrients in gut
• transcription product of proglucagon gene (most from L cells)
• stimulates insulin and suppresses glucagon
• increases satiety
• short half-life due to rapid degradation from dipeptidyl peptidase 4 (DPPG-4)

Question 18

What are DPPG-4 inhibitors used for?

Answer 18

to treat type 2 diabetes mellitus

Question 19

What is the insulin receptor?

Answer 19

• protein/polypeptide hormone that doesn’t cross membranes
• α subunit recognises 3D shape of insulin and causes conformational change in β subunits which cross membranes
• phosphorylation of β subunits important in recruiting substrates that go on to have effects on metabolic pathway
• provides metabolic effect on glucose, amino acids and fatty acids and affects growth

Question 20

What does and doesn’t cause insulin resistance?

Answer 20

• not caused by receptor not being able to recognise insulin or due to transmembrane portion of receptor not working
• lies in post-receptor cytoplasmic elements of insulin function