Biochemistry of Diabetes

Question 1

Inability to move glucose from circulation into energy stores as 3 effects?

Answer 1

1. energy stores are not refilled after a meal and tissues are chronically starved
2. High conc. of glucose in the circulation damages blood and renal vessels (vasculature)
3. High osmotic pressure of extracellular fluids leads to dehydration of tissues

Question 2

Diabetes causes 3 main chronic morbidities

Answer 2

1. blindness due to retinal damage (retinopathy)
2. Nephropathy due to damage to renal vessels
3. Neuropathy due to damage of nerve cells

Question 3

Type I Diabetes: Characteristics, Onset, Treatment

Answer 3

autoimmune destruction of insulin-producing cells in pancreas; strong genetic risk factors; onset from viral infection; treatment= supplying exogenous insulin IN CORRECT AMOUNT

Question 4

Type II Diabetes: Characteristics, Risk Factors, Treatment

Answer 4

Insulin resistance of target tissues; consequence of excessive food intake over time; major risk factor = obesity; 90% of diabetes cases; treatment = weight loss and exercise; drug therapy aims at stimulating insulin secretion, sensitizing peripheral tissues to insulin, reducing intestinal absorption of glucose, repressing GNG

Question 5

Gestational Diabetes

Answer 5

During pregnancy presence of fetus will cause mother’s insulin sensitivity to downgrade allowing fetus to compete for nutrients from mother; if downregulated too much hyperglycemia is a threat to the fetus

Question 6

Impact of insulin on glucose homeostasis (normal)

Answer 6

increases glucose permeability through plasma membranes by GLUT4; stimulates conversion of macronutrients into ATP, glycogen, FA’s and proteins in all tissues; represses GNG

Question 7

Normal impact of insulin on FA homeostasis

Answer 7

stimulates synthesis of FA’s and TAG’s; represses fat mobilization in adipose tissue by inhibiting HSL

Question 8

Insufficient insulin response in diabetic

Answer 8

high serum glucose = vasculature damage and draw water out of tissues; insufficient glucose uptake into cells (cells starved—patient has chronic fatigue); insufficient energy stores (little glycogen to respond to drop in blood glucose between meals = fasting hypoglycemia); elevated fat mobilization from adipose = hyperlipidemia (abundance of free FA’s = ketone bodies); constant hepatic GNG further increasing serum glucose conc.

Question 9

When serum glucose is too high, tissues damaged by 3 processes:

Answer 9

1. spontaneous glycation (addition of glucose residues) of proteins
2. polyol pathway generates sorbitol from glucose (sorbitol = osmotically active, draws water into cells, distortion of cellular structure and tissue)
3. polyol pathway drains NADPH pool by transferring reduction equivalents from NADPH to NAD (weakens cellular antioxidant defenses that rely on NADPH)d

Question 10

Hyperglycemia Characteristics and Effects

Answer 10

kidneys excrete water due to increase in blood volume = polyuria; increased thirst to rehydrate (polydipsia); dehydration and hyperglycemia affect CNS (confusion/disoritented state); coma in extreme cases; will causes drop in serum potassium

Question 11

Hyperlipidemia Characteristics and Effects

Answer 11

increase in VLDL’s and chylomicrons and serum free FA’s; increase in serum lipoproteins and FA’s due to: 1)lipoprotein lipase expression regulated by insulin, w/o LPL around VLDL’s and chylomicrons can’t release lipids; 2) HSL constantly active w/o insulin to shut it off, so continually release of free FA’s into serum, liver takes up FA’s and converts them to VLDLs increasing the VLDL amount in circulation

Question 12

Diabetic Ketoacidosis

Answer 12

seen in type I patients; consequence of unrestrained lipolysis and ketone body prodcution; insulin normally inhibits HSL (releases free FA’s) and CPT1 (takes free FA’s into mito in liver to oxidize and produce ketones); w/o insulin neither enzyme is inhibited and ketones are constantly made and released into blood decreasing blood pH

Question 13

Angiopathy

Answer 13

high serum glucose will damage walls of small and large blood vessels; Macroangiopathy = damage to large vessels = stroke/ myocardial infarction; microangiopathy = damage to small vessels and cuts off supply to peripheral tissues (retina damage)

Question 14

Neuropathy

Answer 14

numbness/tingling in extremities; patient may undergo necrosis of extremities due to bad blood supply, frequently not aware due to neuropathy; lesions occurs and possible amputation

Question 15

Synthesis and Release of insulin

Answer 15

; occurs in beta-cells of pancreatic islets; pre-proinsulin synthesized on ribsomes of ER the cleaved in ER to become proinsulin; goes to golgi where it is further cleaved (C-peptide cleaved off) to become insulin; released from cell by exocytosis

Question 16

What happens when insulin binds to receptor on cell

Answer 16

insulin causes receptor to phosphorylate itself and the -P’s the insulin receptor substrate 1 protein (IRS1); this activates kinase cascades; this ends up DE-PHOSPHORYLATING key enzymes for glycolysis, GNG etc.; in absence of insulin GLUT4 is found on membrane of vesicles in cyto, once insulin binds the GLUT4 receptors translocate to cell surface (rapidly increases uptake of glucose); insulin binding to receptor causes receptor to be internalized (this way cells can control receptor concentration and intensity of the signal)

Question 17

Insulin Effect on Glycogen Metabolism Enzymes:

1. Glycogen Syntase
2. Phosphorylase Kinase
3. Glycogen Phosphorylase

Answer 17

1. increase glycogen synthesis

2. and 3. decrease glycogen degradation

Question 18

Insulin Effect on Glycolysis and GNG:

1. Pyruvate Dehyrdogenase
2. Pyruvate Kinase
3. Phosphofructokinase 2
4. Fructose-2,6,-Bisphosphatase

Answer 18

1 – 3. increase glycolysis

4. decrease GNG

Question 19

Insulin Effect on Lipid Metabolism:

1. Acetyl-CoA Carboxylase
2. HMG-CoA Reductase
3. Hormone Sensitive Lipase
4. Carnitine-Acyltransferase

Answer 19

1. increases FA synthesis
2. increases cholesterol synthesis
3. decreases mobilization of fat
4. decreases ketogenesis

Question 20

Insulin Effects on Protein Synthesis

Answer 20

Increases mRNA of acetyl-CoA carboxylase and FA synthase; decrease in mRNA of PEP carboxykinase (GNG)