Diabetes overview

Question 1

Define diabetes mellitus and describe why it is an important disease

Answer 1

A chronic condition characterized by elevated blood glucose (hyperglycemia). due to an absolute or relative deficiency of insulin. associated with microvascular (and macrovascular) complications

Question 2

Classic symptoms of diabetes

Answer 2

Polydipsia (drinking), polyuria, glycosuria, weight loss. High ketone levels (too much fatty acid conversion to acetyl CoA).

Question 3

Which is increasing more, Type 1 or type 2?

Answer 3

Both going up. Possibly do to epigenetics or environment

Question 4

understand and describe the anatomy of the pancreas, both exocrine and endocrine.

Answer 4

Derived from endoderm, two buds form and come together. In retroperitoneal space. Head (secretes), neck, body, tail (more distal).

Question 5

Islet types

Answer 5

ß cells (insulin); a cells (glucagon); d cells (somatostatin); pp-cells (pancreatic polypeptide - fn unclear). Arranged in decreasing abundance

Question 6

Glucose metabolism overview

Answer 6

Enter via transporter protein, phosphorylated (cannot exit), glycolysis (2 pyruvate and 2 ATP - anaerobic), Krebs cycle (34 ATP - aerobic). Acetyl CoA is intermediate, can come from aa or fatty acid. Energy from krebs cycle works electron transport chain. Gluconeogenesis - can be formed from protein or lipids (glycerol can become glucose, fa can become acetyl CoA). Glycogen - storage; break down from phosphorylase (insulin) and made by glycogen synthase (glucagon).

Question 7

describe the mechanisms responsible for the production of insulin at the level of the cell and the whole organism.

Answer 7

Insulin gene transcript (pre-pro-insulin), cut to proinsulin, then to one insulin and one C peptide (measure how much is being produced despite injections). Preproinsulin is a long chain with di-sulfide bridges. Occurs in granules in ß cells.

Question 8

Secretion of insulin

Answer 8

Glucose enters, higher ATP closes K channel, depolarize membrane, Ca pore opens, causes insulin vesicles to export

Question 9

What else can stimulate insulin secretion?

Answer 9

Parasympathetic stimulation, GI hormones, high aa levels. Sympathetic stimulation is inhibitory

Question 10

Transport of insulin from pancreas

Answer 10

Goes to liver via HPV (primary target - most removed by first pass metabolism), then to insulin sensitive tissues: liver, adipose, muscle

Question 11

Effect of insulin on liver

Answer 11

stimulates hexokinase (G —> G6P), increase glycogen and fatty acid synthesis, increase glucose storage; decrease gluconeogenesis, glycogenolysis, hepatic glucose production

Question 12

Effect of insulin on muscle

Answer 12

Increased glucose uptake (via GLUT-4), increase glycogen synthesis, protein synthesis, amino acid uptake, glucose storage and protein metabolism; decrease glycogenolysis

Question 13

Effect of insulin on fat

Answer 13

increased glucose uptake (via GLUT-4), increase glycerol synthesis, esterification (triglyceride synthesis); decreased lipolysis (hormone sensitive lipase) and non-esterified fatty acids

Question 14

Glucagon actions

Answer 14

On glucose: lower glycogen synthesis, higher gluconeogenesis, glycogenolysis; Lipid: higher lipolysis, lower lipogenesis; Protein: more degradation (minor)

Question 15

describe the mechanisms of insulin action and the effects of insulin on cellular function and metabolism.

Answer 15

Insulin is anabolic. Regulates protein and fat stores. Binds to insulinR, also IGFR (insulin-like GF). Affect cell growth and division; protein, lipid and glucose

Question 16

Mothers that have gestational diabetes often have premature babies or C sections. Why?

Answer 16

Child exposed to high glucose will secrete more insulin, and insulin is a growth factor so they get big!