endocrinology of insulin

Question 1

What do Islets of Langerhans produce

Answer 1

• insulin: secreted by beta cells
• glucagon: secreted by alpha cells
• somatostatin: secreted by gamma cells
• pancreatic polypeptide secreted by F cells

Question 2

proinsulin to insulin mechanism

Answer 2

Proinsulin
cleaved in the Golgi by peptidases
(carboxypeptidase E)
forms insulin and C peptide

2 peptide chains
A (21 aa); B (30 aa)
linked by disulphide bonds

Released
exocytosis

Question 3

how is insulin released from beta cells

Answer 3

• glucose enters the cells by either the GLUT 1 (Km = 1mM) or GLUT2 (Km =15-20mM)
• once glucose enters the cell it gets phosphorylated by glucokinase and the through respiration and glucolysis ATP is formed which increases eat ATP:ADP ratio
• Due to increased levels of ATP, the KATP channel closes because its sensitive to ATP, ATP binds and closes an.d stops efflux of k+ out of the cell of positive charged ions
• accumulation of positively charged ions in the cell causes a change in membrane potential
• membrane becomes depolarised
• this causes membrane dependent voltage channels to open and this causes calcium entry
• the influx of calcium causes insulin storage vesicles exocytosis

Question 4

when you eat insulin is released and enters the hepatic portal vein where it exerts it effects.
how does it effect liver, systemic and fat cells?

Answer 4

insulin enters the hepatic portal vein where it comes across hepatocytes and here insulin

• increases glycogenesis( converting glucose to glycogen
• decreases gluconeogenesis(formation of glucose from protein)
• decrease glycogenolysis
• inrceases protein formation

In the systemic system it works on skeletal muscles myocytes where it

• increases glucose uptake
• increases glycogenesis
• increase protein synthesis

in adipose it

• increases glycogenesis
• increases glucose uptake
• increases protein syntheses

Question 5

what happens when insulin binds to a body cell eg tyrosine receptor

Answer 5

• when insulin binds to the tyrosine receptor it activates the enzyme tyrosine kinase
• this causes phosphorylation of the insulin substrate
• phosporylated insulin substrate causes activation of a series of second messenger pathways
• it can effect transcription factors that effect certain genes, it can increase or decrease levels of certain enzymes and it also effects transport activity of glucose for example GLUT-4

Question 6

regulation of insulin release: sympathetic and parasympathetic system

Answer 6

islet is innervated by both sides of the autonomic nervous system

• B- adrenergic stimulation causes release of insulin
• alpha adrenergic stimulation causes insulin inhibition
• parasympathetic stumulation stimulates insulin release

exercise:
- exercising stimulated alpha adrenergic system to inhibit insulin because your body uses glucose for energy and if insulin is too high this could cause hypoglycaemia

• also body uses fatty acid stores during exercise so insulin inhibition is needed as insulin inhibits lipolysis that needs to happen to access the fatty stores

Question 7

glucocorticoids in the regulation of insulin release

Answer 7

cortisol is the pain human glucocorticoid which is produced in the adrenal cortex from cholesterol

• in muscle cells it breakdown protein to amino acids which can then be readily used to create new glucose via gluconeogenesis
• in the liver it increases levels of gluconeogenic enzymes that utilise the circulating hormones
• it increases glycogenolysis to convert glycogen to glucose

this is all stimulated by a low blood glucose (hypoglycaemia) which is below 3 mol/l, which can be caused by stress, high protein intake and exercise

Question 8

Glucagon in the regulation of insulin release

Answer 8

glucagon is released from alpha cells in response to amino acids from the ingestion of protein

it is formed from proglucagon and processed by PC2 to form glucagon

glucagon prevents hypoglycaemia by stimulating

• glycogenolysis a
• gluconeogenesis

the liver is the primary target and it is released in reposnse to a blood glucose of 3mM

Question 9

How is glucagon released from alpha cells in low blood glucose situations

Answer 9

on the alpha cells there is GLUT-1 receptor which has a Km of 1mM( when blood glucose is 1mM 50% of receptors are occupied

• in low blood glucose situations glucose enters via GLUT-1 and goes through glycolysis to form ATP
• accumulation of ATP causes the closure of KATP channels which causes an accumulation of k+ within the cell
• this causes a moderate depolarisation within the cell which activated voltage gated calcium channels that cause a large influx of calcium
• the entry of calcium stimulates calcium induced exocytosis and therefore glucagon is released which eventually increase blood glucose levels

Question 10

incretins and the regulation of insulin release

Answer 10

There are three incretins

• From the L cells GLP-1 is preduecs
• I cells in the duodenum and jejunum produce CCK

K cells in the duodenum and jejunum produce GIP

all three are released in the gut in response to feeding and cause a release of insulin

that’s why there’s higher insulin conc in plasma when insulin is given orally vs iv as iv bypasses the git

Question 11

role pf somatostatin in insulin regulation

Answer 11

its produced in
- D cells of the stomach and duodenum

• delta cells of pancreatic islets
• exists as both 24(hypothalamus) aa peptides and 28 (delta cells)peptides