Endocrine Pancreas Flashcards
4 types of cells producing hormones
alpha cells- glucagon
beta cells- insulin
delta cells- somatostatin
F cells- pancreatic polypeptide
insulin
polypeptide hormone produced by beta cells in response to hyperglycemia
it is synthesized as a larger molecule inside of the golgi apparatus and packaged into secretory granules awaiting secretion
protein consisting of 2 chains, alpha and beta, that are connected by 2 disulfide bridges
insulin synthesis and secretion
- messenger RNA on the ribosomes of the ER binds amino acids into a peptide chain called a preprohormone. the chain is directed into the ER lumen by a signal sequence of amino acids
- enzymes in the ER chop off the signal sequence, creating an inactive prohormone
- the prohormone passes from the ER through the golgi apparatus
- secretory vesicles containing enzymes and prohormone bud off the golgi. the enzymes chop the prohormone into one or more active peptides plus additional peptide fragments
- the secretory vesicle releases its contents by exocytosis into the extracellular space
- the hormone moves into the circulation for transport to its target
differences in amino acid sequences between species
cattle, sheep, horses, dogs, and whales differ only in positions 8,9, and 10 of the alpha chain
porcine insulin differs from human insulin by one amino acid
bovine insulin differs from cat insulin by one amino acid
porcine and canine insulin are exactly the same
factors affecting insulin secretion
stimuli: Gi hormones such as gastrin, secretin, GIP, glucagon, acetylcholine
inhibitors: somatostatin, epinephrine, norepinephrine
how is insulin released from beta cells?
beta cells have a glucose transporter, GLUT2, in the membrane surface
this allows glucose to diffuse freely into the cell
extracellular fluid glucose concentration directly affects glucose concentration inside of the beta cell
an increase in blood glucose concentration leads to insulin secretion and synthesis
insulin secretion follows biphasic kinetics
acute phase: involves the release of preformed insulin
chronic phase: involves the synthesis of protein
how does insulin act on target cells?
after release, insulin binds to a specific membrane receptor on target tissues
RECEPTOR TYROSINE KINASE
which tissues have insulin receptors?
liver, muscle, fat
physiological action of insulin
the net effect of insulin is to lower blood concentration of glucose, fatty acids, and amino acids
promoting intracellular conversion of glycogen, triglycerides, and proteins to their storage forms
insulin action on muscle and fat
insulin facilitates glucose entry into cells by increasing the number of specific glucose transporters in the cell membranes
GLUT4 is the only insulin sensitive transporter
insulin action on muscle
smooth, striated, and cardiac muscle
stimulates glycogen synthesis enzymes- promoting storage of glucose molecules in the form of glycogen
promotes the use of glucose as a fuel source- reduces fatty acid oxidation, in the absence of insulin, muscle relies on more fatty acids as a fuel source
enhances amino acid uptake which promotes muscle growth
insulin action on adipose tissue
glucose provided to adipocytes promotes: glycerol formation and glycogen synthesis
insulin inhibits lipolysis and promotes adipose deposition
insulin action on liver
promotes fatty acid synthesis in hepatocytes
stimulates incorporation of those fatty acids and triglycerides into lipoprotein bound vesicles such as VLDL for transport to adipocytes
insulin stimulates glycogen synthesis, decreases gluconeogenesis and glycogenolysis
insulin inactivation
is metabolized mainly by the liver and kidneys
specific enzymes reduce the disulfide bonds
chains are subjected to protease activity- reduce them to peptides and amino acids
half life is about 10 minutes
counterregulatory hormones
epinephrine
glucagon
cortisol
growth hormone
glucagon
polypeptide hormone produced by the alpha cells
close relationship with insulin
considerable homology between species
synthesized in the same way as insulin and released by exocytosis
half life of 5 minutes
physiological action of glucagon
opposite of insulin
main effects centered in the liver and greatly enhance the availability of glucose to the other organs of the body
decrease glycogen synthesis
breakdown of liver glycogen
increase liver gluconeogenesis
glucagon synthesis
stimulated by decreased glucose concentration
works with insulin to maintain blood glucose concentration
is high during insulin deficiency- insulin is required for glucose uptake in alpha cells
it is not an opposite hormone in true carnivores: protein ingestion stimulates both insulin and glucagon release. insulin released in response to increased amino acid levels lowers glucose concentration. glucagon counteracts this through increased hepatic gluconeogenesis
pancreatic somatostatin
produced by delta cells in the same way as other protein hormones
inhibitory actions: decreases motility and secretory activity of the GI tract. inhibits secretion of all endocrine cell types of the islet of langerhand. glucagon is more affected than insulin
pancreatic polypeptide
produced by F or PP cells
secretion is stimulated by GI hormones, vagal stimulation, and protein ingestion
inhibition occurs through somatostatin
effects are directed toward the GI tract
increased gut motility and gastric emptying
inhibits secretion of pancreatic enzymes and the contraction of the gallbladder
insulin deficiency
lack or deficiency of insulin produces a syndrome called diabetes mellitus
can be absolute or relative
absolute- type 1
relative- type 2
what does insulin deficiency cause?
lipolysis of storage fat and release of FFA
protein depletion and increased plasma amino acids
type 1 diabetes
characterized by permanent hypoinsulinemia
absolute deficiency. no increase in endogenous insulin after stimulation. absolute necessity for exogenous insulin to maintain control of glycemia. avoid ketoacidosis and survive
common in dogs
potential factors involved in the etiopathogenesis of type 1 diabetes
genetics immune mediated insulitis pancreatitis obesity concurrent hormonal disease drugs infection concurrent illness hyperlipidemia
cataracts in diabetic dogs
most common long term complication
related with altered osmotic relationships in the lens induced by accumulation of sorbitol and galactitol, which are potent hydrophilic agents causing influx of water, which causes swelling and rupture of the lens fibers
type 2 diabetes
characterized by the resistance to the metabolic effects of insulin
relative deficiency- combination of impaired insulin action in the liver, muscle, adipose tissue, and beta cell failure
most common in cats
potential factors involved in the etiopathogenesis of type 2 diabetes
islet amyloidosis obesity pancreatitis concurrent hormonal disease drugs infection concurrent illness genetic hyperlipidemia immune mediated insulinitis
islet of langerhans amyloidosis
amylin is a polypeptide produced and secreted by beta cells together with insulin secretion. it increases satiety, decreases gastric emptying and reduces glucagon production
only humans and cats have the amyloidogenic amino acid structure with the potential to form amyloid deposits within the islets
when amylin aggregates, it formed the amyloid. deposition is toxic to beta cells and leads to dysfunction
common causes of insulin resistance in cats
glucocorticoids progestines acromegaly cushings obesity infection pancreatitis gingivitis hyperthyroidism renal failure IBD
can clinical remission occur in cats with type 2 diabetes
yes, but not if caused by amyloidosis
diabetic neuropathy in cats
most common chronic complication
hyperglycemia leads to nerve injury
pathogenesis not completely understood
