Endocrine Pancreas

Question 1

Where is insulin synthesized?

Answer 1

Beta cells of pancreas (central cells in islets of langerhans)

Question 2

What is insulin originally synthesized as?

Answer 2

Preproinsulin in the RER –> proinsulin

Question 3

Where does proinsulin go to get stored? How it is further modified?

Answer 3

Secretory granules in the golgi. Gets cleaved, forming c-peptide and insulin. Zinc gets added to insulin as well.

Question 4

What is the structure of the resulting insulin?

Answer 4

Two peptide chains “A” and “B” joined by disulfide bonds.

Question 5

When beta cells are stimulated to release insulin, what else gets release? What are the findings of insulinoma vs exogenous insulin?

Answer 5

C-peptide gets released with insulin. Insulinoma will have elevated c-peptide as well, exogenous insulin will not.

Question 6

What happens to insulin when it is released into the blood?

Answer 6

More than half is taken up by the liver.

The remainder binds target tissue.

Question 7

What happens when insulin reaches target tissues?

Answer 7

Binds Insulin receptor AND IGF-1 receptor (if levels high), this initiates a phosphorylation cascades resulting in GLUT-4 being translocated to cell surface, and in downstream cell growth and DNA synthesis.

Question 8

What does GLUT-4 do?

Answer 8

GLUT-4 is an insulin dependent glucose transporter. Present in adipose tissue and striated muscle.

Question 9

What are the anabolic effects of insulin on adipose tissue?

Answer 9

Promotes glucose uptake. Promotes triglycerides synthesis and storage.

Question 10

What are the anabolic effects of insulin on muscle?

Answer 10

Promotes glucose uptake, and glycogen synthesis. Promotes AA uptake and protein synthesis.

Question 11

What are the anabolic effects of insulin on liver?

Answer 11

Promotes glycogen synthesis, FA synthesis, inhibits glucose

output/ketogenesis

Question 12

What is the effect of insulin on glucagon release?

Answer 12

Decreases

Question 13

What is the effect of glucose on the kidneys?

Answer 13

Na+ retention

Question 14

Does insulin cross the placenta? Does glucose?

Answer 14

Insulin doesn’t, glucose does.

Question 15

Where are GLUT-4 transporters located and what increases their expression?

Answer 15

Striated muscle and adipose tissue. Increased expression by insulin and exercise.

Question 16

Where are GLUT-1 transporters located? Are they insulin-dependent?

Answer 16

RBCs, brain, cornea. Insulin-independent.

Question 17

Where are GLUT-2 transporters located? Are they insulin-dependent?

Answer 17

Bidirectional. B-islet cells, liver, kidney, small intestine. Insulin-independent.

Question 18

Where are GLUT-3 transporters located? Are they insulin-dependent?

Answer 18

Brain. Insulin-independent.

Question 19

Where are GLUT-5 transporters located? Are they insulin-dependent?

Answer 19

Spermatocytes, GI tract. Fructose. Insulin-independent.

Question 20

What does the brain metabolize for energy?

Answer 20

Glucose normally, ketone bodies during starvation.

Question 21

What do RBCs metabolize for energy?

Answer 21

Only glucose. Lack mitochondria for aerobic metabolism.

Question 22

Where is glucagon made?

Answer 22

alpha cells of pancreas

Question 23

What is glucagon secreted in response to?

Answer 23

hypoglycemia

Question 24

What is glucagon inhibited by?

Answer 24

insulin, hyperglycemia, and somatostatin

Question 25

What are the functions of glucagon?

Answer 25

Increase glycogenolysis, gluconeogenesis.

Increase lipolysis and ketone production

Question 26

When insulin binds peripheral cells, receptor type is it?

Answer 26

Instrinsic tyrosine kinase

Question 27

What pathway is associated with the insulin receptor?

Answer 27

RAS/MAP kinase pathway –> contributes to cell growth, DNA synthesis
Phosphoinositide-3 pathway -> protein phophtase 1 dephosphorylates glycogen synthase, etc…
Phosphoinositide-3 kinase pathway –> vesicles containing GLUT-4 to membrane

Question 28

In insulin independent cells such as beta cells, what happens as a result of glucose entering cell via GLUT-2?

Answer 28

ATP generated from glucose metabolism

Question 29

What does increased ATP do in pancreatic beta cells?

Answer 29

Closes K+ channels, which depolarizes B-cell membrane

Question 30

What happens when K+ channels of beta cells close?

Answer 30

Membrane is depolarized, Voltage gated Ca2+ channels open

Question 31

What is the result of Ca2+ channels opening in beta cells?

Answer 31

Increases intracellular Ca2+, stimulates insulin exocytosis.