Insulin and Diabetes

Question 1

Islets of Langerhans?

Answer 1

~2% pancreatic mass, ~100microm in diameter, each contains 5,000 cells. 1 million islets, symp and parasymp innervation, 80% is beta cells, 20 % alpha, delta and PP.

Question 2

Insulin production?

Answer 2

Insulin gene is transcribed. mRNA is translated. Proinsulin to secretory granules. peptidase in granules cleaves to insulin and C peptide. Mature insuline + Zn++ = crystals.

Question 3

Insulin secretion?

Answer 3

Glucose enters via Glut-2. Metabolised to increase ATP. KATP shut. Depolarise. VOCC open, Ca++ influx, insulin containing granules exocytosed.

Question 4

Insulin?

Answer 4

A chain - 21AA, B chain 30AA. 2x disulphide bonds. Targets liver, adipose and muscle. Increase glucose uptake - glut2 in liver, glut 4 in adipose and muscle. T1/2= 5 mins.

Question 5

Facts about diabetes.

Answer 5

366 million 4.6 million deaths per year - complications - CV dsyfunction and kidney damage.

Question 6

Type 1?

Answer 6

Insulin dependent.
10%
Autoimmune destruction of B cells.
Progressive.
0.4% risk. - small genetic linkage
Environmental triggers - viruses, cows milk, gluten, nitrosamines, stress

Question 7

Treatment of type 1?

Answer 7

Insulin administration.

Human islet transplants.

Question 8

Type 2?

Answer 8

NIDDM. Central adiposity, insulin resistance, B cell dysfunction, impaired insulin secretion.
90%, larger genetic susceptibility.
Environmental - obesity, western diet, risk decreases with increased exercise.

Question 9

Treatment of Type 2?

Answer 9

Diet, alpha glucosidase inhibitors - inhibit CHO breakdown, decrease BGL.

Sulphonylureas and glitinides - close K+ATP channe;s = stimulate insulin release.

Exenatide - GLP-1 R ag. DPP4 inhibitors - inhibit GLP degradtation - increase insuline release.

Thiazolidinediones - pioglitizone - potentiates insulin.

Biguanides - Potentiates insulin. (metformin).
Increase insulin sensitivity.