Lecture 2 - Pancreas Flashcards
Once Pyruvate is converted to ______, there’s no reversal (i.e. it cannot go through gluconeogenesis at that point).
AcetylCoA
The stimulation of exocrine pancreatic cells occurs simultaneously with stimulation of islet (endocrine) cells via GI hormones. Where are the respective products secreted from the exocrine and endocrine pancreas?
Exocrine –> pancreatic ducts and into the duodenum
Endocrine –> pancreatic vein into the liver
Pancreatic islets are comprised of which cell types?
Alpha cells –> Glucagon
Beta cells –> Insulin
Delta cells –> somatostatin
F cells –> Pancreatic polypeptide (decreases food absorption)
Pre-pro-insulin is uncleaved. Pro-insulin is generated when the _____ _____ is cleaved. Insulin is generated when the _____ peptide is cleaved, leaving the ____ and ____ peptides bound by disulfide bonds (this is the active form).
Signal sequence
C peptide
A and B peptides
Both the bound A-B peptides and cleaved C peptides are brought into secretory granules. How does this allow for measurement of Beta cell function in a patient receiving exogenous insulin?
Measurement of C peptide will show Beta cell function bc it is not part of exogenous insulin.
Insulin half-life is ____ mins.
5mins
Secretion of insulin from the beta cell is as follows:
Increase in Glucose –> uptake into Beta cell via _____ –> increased activity of ________ (which has a low affinity for glucose, so it requires a high concentration of glucose to be very active) –> increased intracellular production of _____ –> inhibition of _____-sensitive K+ channels –> depolarizes the cell –> influx of Ca++ via ____-gated Ca++ channel –> secretion of insulin via binding of secretory granules with plasma membrane.
GLUT 2
Glucokinase
ATP
ATP-sensitive K+ channel
Voltage-gated Ca++ channel
Glucose and AAs that feed into the citric acid cycle are key stimulators of Insulin secretion. So too are Glucagon, GLP-1, GIP, CCK, and ______ (medication).
How does that last one work?
Sulfonylureas
They block ATP-sensitive K+ channels –> depolarized Beta cells –> so on until insulin secretion.
__-_______ is an exogenous inhibitor of Glucose. _____ and Catecholamines (via ___-adrenergic receptors) also inhibit Insulin secretion. _____ is the opposite of Sulfonylureas, so it inhibits Insulin secretion by OPENING ATP-sensitive K+ channels.
2-Deoxyglucose
Somatostatin
Alpha-adrenergic
Diazoxide
GLUT-2 transporters are found in pancreatic islets and in the ______. How do GLUT-2 transporters compare to GLUT-4 regarding glucose affinity?
Liver
GLUT-2 has lesser affinity (Km between 12-20 mM, while that of GLUT-4 is about 5mM).
Why does insulin stimulate Glycolysis in the Liver and in Adipose tissue?
This provides substrate for lipid/fatty acid synthesis.
Glucagon’s half-life is about ___-___mins. It almost exclusively acts in the liver, as it is secreted into the _____ vein.
5-10mins
Portal vein
Remember that Glucagon _____ (stimulates or inhibits?) insulin secretion, but Insulin ______ (stimulates or inhibits?) Glucagon secretion.
Stimulates
Inhibits
ACh, Catecholamines (acting on ____-adrenergic receptors), Cortisol, and Exercise all ______ (stimulate or inhibit?) Glucagon secretion.
Beta-adrenergic
Stimulate
SST secretion is stimulated by the same stimuli that increase _____ secretion, particularly _____ and ____. Keep in mind SST decreases Glucose transport across the gut wall and decreases blood flow.
Insulin
Glucose
AAs
Epi acts on the liver by stimulating the same processes ______ stimulates. In muscle, Epi inhibits _____ and stimulates glycogen breakdown to ______ (which can then be used as a substrate for Gluconeo in the liver) via the Kori cycle.
Glucagon
Insulin
Lactic Acid
The major effect of Cortisol is to stimulate mobilization of _____ (primarily from _____ tissue) and their conversion to glucose in the liver.
Cortisol also inhibits actions of insulin in ____ and _____ (which tissues?).
Interestingly, Cortisol causes mobilization of _____ from adipose tissue, but it can also facilitate _____ storage in select adipose tissue sites.
Keep in mind (big point here) Cortisol increases blood glucose like Glucagon and Epi, but it differs in that it stimulates deposition of ______.
AAs
Muscle
Muscle and Fat (peripheral tissues)
Fat
Fat
Glycogen
Diabetes mellitus is diagnosed with a glucose tolerance test. If at 2 hours post-administration of glucose the patient’s blood glucose level is above ______g/dL and was above this mark at one or more points throughout the 2 hours, this is Diabetes Mellitus. If the 2 hour level is below _____g/dL and there were no points above ____g/dL, this is normal. Anywhere in between is considred impaired glucose tolerance.
200g/dL
140g/dL
200g/dL
HbA1c classification of diabetes:
Normal range = ___-___%
Prediabetic = ____-____%
Diabetic = ____% and above.
Normal = 4.5-5.6%
Prediabetic = 5.7-6.4%
Diabetic = 6.5% and above