Endocrine Pancreas Flashcards
what is secreted in response to CHO- and/or protein ingestion?
insulin
what is the major stimulatory factor of insulin secretion?
glucose
what do the endocrine cells of the pancreas secrete?
insulin, glucagon, and somatostatin
how are the endocrine cells of the pancreas arranged?
in clusters known as islets of langerhans
what are the endocrine cells of the pancreas?
beta-cells, alpha-cells, delta-cells, and F-cells
what do the beta cells secrete?
insulin and C peptide
what do the alpha-cells secrete?
glucagon
what do the delta-cells secrete?
somatostatin
what do the F cells secrete?
pancreatic polypeptide
which cells are destroyed in a type 1 diabetic?
beta cells
what is the role of the F cells and their secretions?
they act like a satiety signal (neuropeptide Y, peptide YY family)
how do the endocrine cells of the pancreas/islets communicate with each other?
via gap junctions and blood supply
how does the arterial supply come into the islets?
it comes into the center and is going to primarily bathe the beta-cells
what kind of hormone is insulin?
peptide hormone
what is secreted at the same time as insulin?
C peptide
what does insulin signal the liver to do?
the liver senses the insulin and will stop producing glucose out into the bloodstream
how does glucose enter the beta-cell?
via GLUT-2
what happens once glucose enters the beta-cell?
it is phosphorylated by glucokinase into glucose-6-phosphate
what happens to the glucose-6-phosphate?
it is oxidized, which promotes ATP generation
what effect do the rising ATP levels have in the beta-cell?
ATP closes the “inward-rectifying” K+ channel (so the plasma membrane is a little more positive on the interior)
what happens when the inward rectifying K+ channels are closed?
the plasma membrane is a little more positive on the interior–> the plasma membrane is depolarized
what happens when the plasma membrane of the beta-cells is depolarized?
there is activation of the voltage-gated Ca2+ channels and Ca2+ enters the cell
what happens when Ca2+ enters the beta-cells?
it initiates mobilization of insulin and C peptide containing vesicles to plasma membrane and exocytosis
what drugs target the ATP-dependent K+ channels to increase insulin secretion?
sulfonylurea receptor drugs
what is a general characteristic of insulin release?
it is biphasic- there is an initial spike within minutes and a further increase half an hour to an hour later
what phase of insulin secretion is lost first in type 2 diabetics?
the first phase
where does insulin resistance primarily occur?
adipose tissue and skeletal muscle
what happens through AKT?
it signals to vesicles containing GLUT-4 to move to the plasma membrane and insert the GLUT-4 into the membrane. It then allows glucose to move into the cell, which will in turn lower the blood glucose levels
what is a hypothesis on why the intracellular signaling gets “mucked up”?
mitochondrial overload- they have byproducts of metabolism that cause of family of stress kinases to inhibit and block what this intracellular signaling should do
what happens to the incretin effect in T2DM?
it is abolished
what are the stimulatory factors of insulin secretion?
increased glucose/amino acid/fatty acid/ketoacid concentration, glucagon, cortisol, GIP, CCK, GLP-1, vagal stimulation (ACh), sulfonylurea drugs
what are the inhibitory factors of insulin secretion?
fasting, exercise, somatostatin, norepinephrine, diazoxide
what effect does insulin have on K+?
there is an increased K+ uptake into the cells and therefore decreased K+ in the blood level
what does muscle contraction activate?
AMP-Kinase (AMPK), which results in GLUT4 translocation to the plasma membrane and then glucose uptake
what is the effect of glucagon?
it increases blood glucose levels
what is the secretion of glucagon stimulated by?
decreased blood glucose (major), increased AAs, fasting, B-adrenergic agonists, ACh
what inhibits glucagon?
insulin and high blood glucose levels and somatostatin
what is the major factor contributing to development of T2DM?
multiple genes coupled with environment
what ethnic group is more at risk for developing T2DM?
african americans, hispanic, and Pima native americans
what happens when adipose tissue becomes inflammed?
they recruit macrophages, which then tell the adipocytes to become more dysfunctional and start releasing more inflammatory factors
what are some pro-inflammatory cytokines?
IL-6, TNF-alpha, CRP
what is the step after systemic insulin resistance?
reactive hyperinsulinemia- after eating a meal, glucose levels are normal but more insulin required
what happens after hyperinsulinemia?
postprandial hyperglycemia
when do symptoms become evident of T1DM?
not until ~80% of Beta cells are destroyed
how do you get diabetic ketoacidosis (DKA)?
if there is decreased utilization of ketoacids
besides inadequate insulin secretion, what else happens in T1DM patients?
hyperkalemia and osmotic diuresis
is a family history more prominent for type 1 or type 2 diabetes?
type 2
what is an example of a gene that is predominantly mutated in cases of T1DM?
DQ2/DQ8 gene
