Insulin, Glucagon, GLP-1, and Counter-Regulatory hormones Flashcards
There are three types of endocrine cells in the pancreatic islets: _________________.
beta cells: insulin
alpha cells: glucagon
delta cells: somatostatin
There are two kinds of hormones: _________________.
(1) Water-soluble molecules that associate with membrane receptors; these work quickly by acting through membrane receptors.
(2) Lipid-soluble molecules that circulate bound to proteins and pass freely through the membrane; these work slowly, because they alter transcription.
Insulin is secreted as _________ and gets ______________.
proinsulin; cleaved by proteases such that the C-peptide is removed (this can be measured as an indicator of endogenous insulin creation, because pharmacologic insulin will not have this)
Glucose enters beta cells through the _________ transporter.
GLUT2 (the non-insulin-sensitive receptor)
How do beta cells sense glucose and secrete insulin?
Glucose increases intracellular ATP which decreases potassium current, causing depolarization. The depolarization induces calcium entry and thus insulin exocytosis.
Activation of the membrane insulin receptor leads to two main pathways. What are they? (Dr. Bessesen specifically said to know these.)
MAP-kinase: ERK signaling to induce vasoconstriction and growth
PI3-kinase: Akt signaling to induce GLUT4 translocation and NO production
Those with insulin-resistant diabetes are at increased risk of cancer because ______________.
there is no resistance to the mitogenesis signaling of insulin
GLUT4 translocation occurs by ___________.
exocytosis of vesicles containing insulin receptors (from PI3-K)
IRS is __________.
insulin receptor substrate – the molecule activated by the insulin surface receptor
In addition to blunted insulin response, type II diabetes is characterized by ______________.
inadequate glucagon suppression after meals
What does glucagon-like peptide 1 do?
When you eat, the intestines signal to the pancreas that that more insulin is needed and less glucagon is needed.
What enzyme inhibits GLP-1?
DPP-4 (this enzyme can be inhibited/blocked by drugs and thus increase insulin secretion and decrease glucagon secretion)
Insulin is stored in hexamers containing ____________.
two zinc ions
True or false: glucose is the only molecule that can stimulate insulin release in beta cells.
False. Amino acids also can, although fats cannot.
Why does epinephrine decrease insulin release?
It’s thought that during exercise (when epinephrine would be released), you want blood glucose to rise. As such, inhibiting insulin is a way to do that.
Alloxan and streptozocin are use to ____________.
create models of diabetes in animals, because they selectively kill beta cells
The insulin receptor belongs to the ______________ family of receptors. The alpha portion binds insulin and the beta portion spans the membrane.
epidermal growth factor
When activated, the insulin receptor _____________-.
phosphorylates itself and then phosphorylates other substrates
Insulin stimulates vasodilation through the ______________ and vasoconstriction through the _______________.
PI-3 kinase pathway; MAP kinase
Glucagon also stimulates these non-insulin mechanisms: _______________.
lipolysis in adipose tissue and ketogenesis in hepatocytes
The alpha cells of the pancreas require insulin to import glucose. Why is this important in type 2 diabetes?
Because insulin resistance makes the alpha cells think the body is hypoglycemic even when it is hyperglycemic. Thus, glucagon will be secreted in those with type 2 diabetes even when glucose levels are high.
