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
