Endocrine Pancrease

Question 0

Pancreas development

Answer 0

Develops from dorsal pancreatic bud off future duodenum
Cells differentiate into acinar cells and ducts (exocrine)
Cells adjacent to ducts develope in to islets (endocrine)

Question 1

Isolated endocrine cells of GI tract

Answer 1

Enteroendocrine cells
Peptide and amine hormones are secreted by the gut wall
Regulate activity of GI tract, pancreas, etc
May be located at any level
Responsive to gut contents
Open type->secreted on surface
Closed type->responsive to changes in tissue environment
Cells containing granules in amongst other GI cells
May form enteroendocrine tumour

Question 2

Islet distribution

Answer 2

25% in head
25% in uncinate process
20% in body
30% in tail

Question 3

Histology of pancreas

Answer 3

Groups of cells clumped together surrounded by capillary bed of islet
Paler staining circular groups
Glucagon positive alpha cells-> 18%-> homogenous dense spheres
Somatostatin positive D cells-> 3%-> heterogenous large spheres
Insulin positive beta cells->75%-> homogenous crystals, loose membrane

Question 4

Insulin structure

Answer 4

A chain-> 21aa 
Joined to B by disulphides bridges 
B chain-> 30aa
C chain-> 31aa no biological activity 
Half life 5-9 mins
Initially secreted as proinsulin 86aa

Question 5

Biosynthesis of insulin

Answer 5

RER-> preproinsulin-> cleavage of signal sequence
Golgi-> proinsulin transfer-> secretory granules->proinsulin->cleavage of C peptides-> insulin
Pro converses-> PC
PC 2 cleaves at 65-66 A end
PC 1 cleaves at 32-33 B end
CPH removes 64-65 of C peptide
Carboxypeptidase H removes 31-32
1:1 insulin:C peptide packaged in secretory granule
2Zn2+:6 insulin, crystallised core in secretory granules-> condensation of insulin with Zn-> insoluble so stored
Released by exocytosis-> involves Ca and ATP
Defects in processing enzyme-> hyperproinsulinaemia-> type 2-> secretion of proinsulin in response to increase insulin response

Question 6

Stimulation of insulin release

Answer 6

Nutrient stimulus: 
Blood glucose >5mM 
Rise in ATP:ADP ratio-> closer of ATP sensitive K channels-> membrane depolarisation-> opening of Ca channels-> insulin release
Beta cells take up glucose 
Potentiators: 
Gut hormone GLP1 and GIP 
Incretins
Glucagon inhibits insulin, somatostatin inhibits glucagon

Question 7

Simulation of insulin release, Paracrine effect

Answer 7

Peak of insulin much higher and happens faster with oral glucose than intravenous
60% of post meal insulin secretion due to Incretins
Glucose in gut causes secretion of Incretins in to blood

Question 8

Neural control of insulin secretion

Answer 8

Sympathetic beta adrenoceptors-> increase insulin release
Sympathetic alpha 2 adrenoceptors->decrease insulin release-> more of this so overall decrease caused by sympathetic stimulation
Parasympathetic-> muscarinic-> increases insulin release

Question 9

Glucagon

Answer 9

Peptide hormone 29aa
Synthesised as pro glucagon in islet alpha cells
Release:
Stimulated by low blood glucose appose insulin

Question 10

Somatostatin

Answer 10

Peptide hormone of 14aa
Synthesised as pro hormones in islet cells
Inhibits glucagon and insulin

Question 11

Insulin action

Answer 11

Promote growth and development
Promote cellular uptake of K via Na/K ATPase
Promote uptake and utilisation of glucose in skeletal muscle and adipose
Promote fuel storage
Increase rate of synthesis and storage of glycogen, fat and protein

Question 12

Physiologically effects of insulin

Answer 12

Decrees blood glucose
Liver:
Decrease glycogen synthesis, glycogen breakdown and gluconeogensis
Muscle:
Increase glucose uptake and protein synthesis, decreased protien breakdown
Adipose:
Increase glucose uptake and lipogenesis, decreased lipolyisis

Question 13

Physiological effects of glucagon

Answer 13

Increase blood glucose
Stimulate hepatic gluconeogensis
Stimulate hepatic gluconeogenlysis
Stimulate lipolyisis