Single-membrane organelle present in nearly all eukaryotic cells. It contains peroxidase and catalase.

Most important event: beta-oxidation of long chain fatty acids

alpha, beta, and gamma PPAR

endogenous ligand: fatty acids, PG, leukotrienes

exogenous: drugs

Ligands: retinoids

dimerizes with PPAR- doesn't matter which one you activate- either way induce generation of dimers

attach to nucleus response element

induce production of something

requires time (hours)

ligand activated transcription factors

upon binding to fatty acids or hypolipidemic drugs (fibrates), PPAR-alpa interacts with RXR and regulates the expression of target genes. These genes are involved in the catabolism of fatty acids--> lipoprotein lipase goes up--> PPAR-alpha: hyperlipidemia

activated by PGs, leukotrienes and anti-diabetic thiazolidinediones (glitazones?-lower sugars) and affects the expression of genes invovled in the storage of the fatty acids and others --> clinically insulin sensitivity goes up

PPAR-gamma: diabetes

PPAR-alpha: hyperlipidemia

clofibrate

genfibrozil (older)

fenofibrate

bezafibrate

ciprofibrate

Effects: down TGs**; down cholesterol (modest); down VLDL; up HDL; up and down LDL

fibrate

side effects: gall stones; LFT

Warning! when combined with statins: elevated rhabdomyolysis

displace warfarin from protein binding site

-glitazone

PPAR-gamma: diabetes

Troglitazone- withdrawn in 2000

Rosiglitazone

Pioglitazone

improves glycaemic control in people with Type 2 diabetes by inproving insulin sensitivity throught its action at PPAR-γ, and affects lipid metabolism through action at PPAR-γ

increase glucose transporters; lowered free fatty acids; enhanced insulin signalling; reduced TNFa; remodeling of adipose tissue

--> reducing insulin resistance

do not cause hypoglycemia

advantage over SU & repaglinide

- slow in onset (2-6) weeks

hemoglobin is a protein in RBCs that carries O2. Hemogloin picks up glucose from the bloodstream, becoming "glycated" As blood glucose rises, so does the level of glycated hemoglobin.

Once hemoglobin becomes glycated, it remains that way for the life of the RBC, which is 3-4 months. This means the HbA1c test can provide a pictures of your glucose control over several months.

** want under 7

hepatic toxicity

edema not responding to diuretics

increased circulating volume

heart failure

weight gain

paresthesias

elevations of creatinine phophokinase (CPK)

Might:

extensive hepatic metabolism

reinstate ovulation in post-menopausal women

decrease steroid levels: loss of contraceptive effect