Endocrine Pancrease Flashcards
Pancreas development
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)
Isolated endocrine cells of GI tract
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
Islet distribution
25% in head
25% in uncinate process
20% in body
30% in tail
Histology of pancreas
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
Insulin structure
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
Biosynthesis of insulin
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
Stimulation of insulin release
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
Simulation of insulin release, Paracrine effect
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
Neural control of insulin secretion
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
Glucagon
Peptide hormone 29aa
Synthesised as pro glucagon in islet alpha cells
Release:
Stimulated by low blood glucose appose insulin
Somatostatin
Peptide hormone of 14aa
Synthesised as pro hormones in islet cells
Inhibits glucagon and insulin
Insulin action
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
Physiologically effects of insulin
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
Physiological effects of glucagon
Increase blood glucose
Stimulate hepatic gluconeogensis
Stimulate hepatic gluconeogenlysis
Stimulate lipolyisis