Jan 20 - Hormones of the pancreas and intermediate metabolism

Question 1

Name the hormones for glucose metabolism. Where are they secreted from?

Answer 1

The pancreas secretes insulin and glucagon
The adrenal gland secretes cortisol and epinephrine
The pituitary gland secretes growth hormone

Question 2

Which hormone(s) reduce(s) blood glucose?

Answer 2

Insulin

Question 3

Which hormone(s) raise(s) blood glucose?

Answer 3

Glucagon, cortisol, epinephrine, growth hormone

Question 4

What is considered a normal insulin level?

Answer 4

5-6 mmol

Question 5

Describe the histology of the pancreas

Answer 5

The pancreas is made up of two cell types: endocrinic islets of Langerhans and exocrinic acini. The islets make up about 15-20% of the pancreas. The acini make up the remainder of the pancreas and they secrete digestive enzymes into the duodenum.

Question 6

What are the different cell types of the islets of Langerhans? What do they secrete?

Answer 6

Alpha cells secrete glucagon
Beta cells secrete insulin
Delta cells secrete somatostatin
F cells secrete pancreatic polypeptide

Question 7

Describe insulin (and proinsulin)

Answer 7

Proinsulin is made up of three chains: A chain, B chain and C chain. C peptide has no known function and proinsulin as little biological activity. A and B chains are connected by two disulfphide covalent bonds between cysteine residues. Posttranslational processing occurs in the Golgi and secretory granules. The C chain is cleaved away by proprotein convertase. Mature insulin (complexed with Zn++) and the C peptide are released from granules by exocytosis

Question 8

Name stimulants of insulin release

Answer 8

Sugars (glucose, mannose)
Amino acids (leucine)
Vagus nerve stimulation (ex. if you smell food)
Sulfonylureas

Question 9

Name amplifiers of glucose-induced insulin release

Answer 9

Enteric hormones (e.g., gastrin, secretin, cholecystokinin)
Neural amplifiers (beta-adrenergic effect of catecholamines)
Amino acids (arginine)

Question 10

Name inhibitors of insulin release

Answer 10

Neural (alpha-adrenergic effect of catecholamines)

Humoral (somatostatin’s paracrine action)

Question 11

What does insulin promote?

Answer 11

Glucose uptake into cells (liver, adipose, muscles)
Glycogen synthesis (liver)
Lipid synthesis (adipose)
Protein synthesis by increasing amino acid uptake
Thus insulin is anabolic

Question 12

What is responsible for glucose uptake into cells

Answer 12

Glucose uptake into cells is mediated by facilitated diffusion using glucose transporters: GLUT1 through GLUT5

Question 13

Describe GLUT1

Answer 13

It’s found in the brain endothelium (it’s not sensitive to insulin)

Question 14

Describe GLUT2

Answer 14

Release glucose from cells (liver, fat, muscle)
It is not sensitive to insulin
It acts as “glucoreceptors” in beta cells to release insulin

Question 15

Describe GLUT3

Answer 15

Found in neurons (not sensitive to insulin)

Question 16

Describe GLUT4

Answer 16

Very sensitive to insulin in uptaking glucose into cells

Question 17

Describe GLUT5

Answer 17

Found in the gut (responsible for the uptake of ingested glucose)

Question 18

Describe glucagon

Answer 18

It is produced by alpha cells of the islets of Langerhans
It’s potent releaser of glucose
It stimulates gluconeogensiss (production of glucose from non-glucose sources)
Stimulates lipolysis

Question 19

What is diabetes mellitus?

Answer 19

A syndrome of disordered metabolism with inappropriate hyperglycemia due to:

• a deficiency of insulin, or
• a reduction in effectiveness of insulin, or
• both

Question 20

What are two types of diabetes mellitus?

Answer 20

Type I and type II

Question 21

Describe type I diabetes mellitus

Answer 21

It’s caused by the destruction of beta cells. It’s prevalence is about 10. Insulin levels are low to absent

Question 22

Describe type II diabetes mellitus

Answer 22

It’s a metabolic syndrome. It’s prevalence is about 80-90%. Early on, the insulin levels are normal to high, but as the disease progresses, they become low. 85% of type II DM patients are obese

Question 23

What does insulin deficiency cause?

Answer 23

Decreased glucose uptake
Increased hepatic gluconeogenesis
Increased lipolysis and ketone
Increased protein breakdown

Question 24

What does decreased glucose uptake cause?

Answer 24

Hyperglycemia, glycosuria, osmotic diuresis > dehydration, loss of electrolytes > cardiovascular depression > shock, coma, death (also caused by dehydration and loss of electrolytes)

Question 25

What does increased hepatic gluconeogensis cause?

Answer 25

Same thing as decreased glucose uptake

Question 26

What does increased lipolysis and ketone cause?

Answer 26

Ketosis, acidosis > vomiting/cardiovascular depression > dehydration, loss of electrolytes > shock, coma, death

Question 27

What does increased protein breakdown cause?

Answer 27

Nitrogen loss in urine

Question 28

What does glucose toxicity cause?

Answer 28

Glucose toxicity - oxidative stress due to increase in oxygen radicals; alterations of protein glycosylation (glycation) and functions (e.g. glycated haemoglobin, HbA1c)

Question 29

What are chronic complications due to diabetes mellitus?

Answer 29

Opthalmologic complications (diabetic retinopathy, cataracts)
Renal complications (diabetic nephropathy, infections)
Neurological problems (diabetic neuropathy - sensory, motor, autonomic)
Cardiovascular defects (cardiomyopathy, myocardial infarction)

Question 30

What is the primary treatment for type I diabetes mellitus?

Answer 30

Insulin, nature of dietary intake

Question 31

What is the primary treatment for type II diabetes mellitus?

Answer 31

Nutritional therapy - weight loss (diet, exercise)

Pharmacological therapy

Question 32

What are different pharmacological therapies available for the treatment of type II diabetes mellitus?

Answer 32

Biguanides
Sulfonylureas
Other secretagogues
Thiazolidinediones
Glucosidase inhibitors
Insulin

Question 33

What are biguanides? Give an example

Answer 33

Hypoglycemic agents that inhibit gluconeogensis. Ex. Metformin

Question 34

What are sulfonylureas?

Answer 34

Insulin secretagogues (ex. glyburide)

Question 35

What is an example of another secretagogue?

Answer 35

Repaglinide

Question 36

What are thiazolidinediones?

Answer 36

They increase sensitivity to insulin (ex. rosiglitazone)

Question 37

What are glucosidase inhibitors

Answer 37

Inhibit digestion of complex carbohydrates, hence reduce sugar availability (ex. acarbose)