Endocrine 6 - Pancreas

Question 1

Is there a positive correlation between BMI and relative risk for Type 2 diabetes?

Answer 1

Yeah

Question 2

What are the four symptoms of a newly diagnosed Type 1 diabetic?

Answer 2

1. Rapid weight loss
2. Polydipsia
3. Polyuria
4. Polyphagia

Question 3

Why does Type 2 diabetes cause polyuria?

Answer 3

Blood glucose levels overwhelm the Na+/Glucose transporters, glucose in the tubules pulls water in with it –> increased urine output.

Question 4

What are the four major pancreatic cell types and what does each do?

Answer 4

beta cells (insulin), alpha cells (glucagon), delta cells (somatostatin - inhibitory), acinar cells (digestive enzymes).

Question 5

What is C-peptide and what is its clinical significance?

Answer 5

It is part of pre-proinsulin that is cleaved off in the ER during post-translational modification. It is useful clinically to determine if patient insulin levels are due to endogenous or exogenous sources of insulin (if endogenous, levels of C-peptide should match insulin levels).

Question 6

What are the criteria for diagnosing someone as a diabetic?

Answer 6

Fasting glucose > 126 mg/dL
2 hour glucose > 200 mg/dL
> 6.5% HbA1c

Question 7

Insulin release is ________, exhibiting two separate peaks in serum concentration levels if blood glucose levels remain high.

Answer 7

biphasic

Question 8

Name five stimulators and one inhibitor of insulin synthesis and release.

Answer 8

Stimulants:

1. Glucose
2. AAs
3. Gastric inhibitory peptide
4. Glucagon-like peptide
5. Vagus nerve activity

Inhibitor: Somatostatin

Question 9

Describe the mechanism by which glucose triggers insulin gene transcription and insulin release in beta cells.

Answer 9

Glucose enters via GLUT 2 transporter –> glucokinase converts glucose to G6P, traps glucose in the cell –> glycolysis –> higher ratio of ATP/ADP triggers closure of ATP-sensitive K+ channel –> membrane depolarization –> influx of Ca2+ –> fusion of insulin containing granules and vesicles –> insulin secretion and transcription of insulin genes in the nucleus.

Question 10

Why do plasma insulin levels rise disproportionately more when glucose is ingested orally vs. when it is given via IV infusion?

Answer 10

Incretins (gastric inhibitory peptide and glucagon-like peptide) are released from gastric mucosal cells upon ingestion of glucose, which triggers insulin secretion.

Question 11

What type of receptor does GLP-1 bind and what second messengers are triggered?

Answer 11

7 transmembrane receptor –> adenylate cyclase –> cAMP and PI3 kinase.

Question 12

Insulin stimulates skeletal muscle and adipose tissue to fuse increased numbers of ________ transporters in the plasma membrane, allowing for greater uptake of glucose.

Answer 12

GLUT4

Question 13

What type of receptor is the insulin receptor? Describe the pathway involved after it binds insulin.

Answer 13

A tyrosine kinase receptor.

Insulin binds –> conformational change in receptor, activating kinase activity –> phosphorylation of IRS-1 –> phosphorylation of PI3 kinase –> GLUT4 receptors go to the plasma membrane.

Question 14

Is the insulin receptor synthesized as a single polypeptide, and cleaved post-translationally, with disulfide bonds that link the different subunits together?

Answer 14

Yeah

Question 15

How is insulin cleared from the blood?

Answer 15

1. Liver degrades it

2. When insulin binds its receptor, the receptors are endocytosed (along with the insulin)

Question 16

What organ is the major target of glucacon?

Answer 16

The liver

Question 17

What two things stimulate glucagon synthesis and secretion? What two things inhibit it?

Answer 17

Stimulants:

1. AAs
2. Epinephrine

Inhibitors:

1. Glucose
2. Somatostatin

Question 18

Through what receptor pathway does glucagon work?

Answer 18

7 TM receptor –> adenylate cyclase makes cAMP –> PKA –> increased gluconeogenesis, decreased glycolysis and glycogenesis.

Question 19

What happened to the diabetic mice that had their glucagon receptors knocked out?

Answer 19

They had more normal levels of blood glucose.

Question 20

Diabetic ketoacidosis is a major risk factor for which type of diabetes?

Answer 20

Type 1

Question 21

Name four major and common complications of DM.

Answer 21

1. Leaky capillaries
2. Neuropathy
3. Impaired wound healing
4. Hypoglycemia (from taking too much insulin, not eating enough)

Question 22

A patient with an insulin-producing tumor (insulinoma) will have elevated circulating insulin and:

a) elevated blood glucose
b) reduced circulating proinsulin
c) elevated insulin connecting peptide
d) reduced glucagon
e) elevated insulin receptors on target tissues

Answer 22

c) elevated insulin connecting peptide

Question 23

The effects of insulin on skeletal muscle include all of the following EXCEPT:

a) increased glucose transport
b) increased amino acid transport
c) increased glycogen synthesis
d) increased protein degradation
e) increased protein synthesis

Answer 23

d) increased protein degradation

Question 24

A common stimulator of secretion of both insulin and glucagon is:

a) amino acids
b) somatostatin
c) stimulation of the vagus nerve
d) glucose
e) GIP

Answer 24

a) amino acids

Question 25

Type 1 diabetes mellitus is most commonly caused by:

a) reduced insulin receptor number on target cells
b) a mutation that blocks the processing of preproinsulin
c) autoimmune-mediated destruction of b-cells in the islets
d) improper movement of GLUT4 transporters to the plasma membrane
e) the absence of insulin receptor tyrosine kinase activity

Answer 25

c) autoimmune-mediated destruction of b-cells in the islets