Lecture 2 - Pancreas

Question 1

Once Pyruvate is converted to ______, there’s no reversal (i.e. it cannot go through gluconeogenesis at that point).

Answer 1

AcetylCoA

Question 2

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?

Answer 2

Exocrine –> pancreatic ducts and into the duodenum

Endocrine –> pancreatic vein into the liver

Question 3

Pancreatic islets are comprised of which cell types?

Answer 3

Alpha cells –> Glucagon

Beta cells –> Insulin

Delta cells –> somatostatin

F cells –> Pancreatic polypeptide (decreases food absorption)

Question 4

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).

Answer 4

Signal sequence

C peptide

A and B peptides

Question 5

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?

Answer 5

Measurement of C peptide will show Beta cell function bc it is not part of exogenous insulin.

Question 6

Insulin half-life is ____ mins.

Answer 6

5mins

Question 7

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.

Answer 7

GLUT 2

Glucokinase

ATP

ATP-sensitive K+ channel

Voltage-gated Ca++ channel

Question 8

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?

Answer 8

Sulfonylureas

They block ATP-sensitive K+ channels –> depolarized Beta cells –> so on until insulin secretion.

Question 9

__-_______ 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.

Answer 9

2-Deoxyglucose

Somatostatin

Alpha-adrenergic

Diazoxide

Question 10

GLUT-2 transporters are found in pancreatic islets and in the ______. How do GLUT-2 transporters compare to GLUT-4 regarding glucose affinity?

Answer 10

Liver

GLUT-2 has lesser affinity (Km between 12-20 mM, while that of GLUT-4 is about 5mM).

Question 11

Why does insulin stimulate Glycolysis in the Liver and in Adipose tissue?

Answer 11

This provides substrate for lipid/fatty acid synthesis.

Question 12

Glucagon’s half-life is about ___-___mins. It almost exclusively acts in the liver, as it is secreted into the _____ vein.

Answer 12

5-10mins

Portal vein

Question 13

Remember that Glucagon _____ (stimulates or inhibits?) insulin secretion, but Insulin ______ (stimulates or inhibits?) Glucagon secretion.

Answer 13

Stimulates

Inhibits

Question 14

ACh, Catecholamines (acting on ____-adrenergic receptors), Cortisol, and Exercise all ______ (stimulate or inhibit?) Glucagon secretion.

Answer 14

Beta-adrenergic

Stimulate

Question 15

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.

Answer 15

Insulin

Glucose

AAs

Question 16

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.

Answer 16

Glucagon

Insulin

Lactic Acid

Question 17

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 ______.

Answer 17

AAs

Muscle

Muscle and Fat (peripheral tissues)

Fat

Fat

Glycogen

Question 18

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.

Answer 18

200g/dL

140g/dL

200g/dL

Question 19

HbA1c classification of diabetes:

Normal range = ___-___%

Prediabetic = ____-____%

Diabetic = ____% and above.

Answer 19

Normal = 4.5-5.6%

Prediabetic = 5.7-6.4%

Diabetic = 6.5% and above