Effects of the PPARgamma agonist pioglitazone on lipoprotein metabolism in patients with type 2 diabetes mellitus.
Elevated plasma levels of VLDL triglycerides (TGs) are characteristic of patients with type 2 diabetes mellitus (T2DM) and are associated with increased production rates (PRs) of VLDL TGs and apoB. Lipoprotein lipase-mediated (LPL-mediated) lipolysis of VLDL TGs may also be reduced in T2DM if the level of LPL is decreased and/or the level of plasma apoC-III, an inhibitor of LPL-mediated lipolysis, is increased. We studied the effects of pioglitazone (Pio), a PPARgamma agonist that improves insulin sensitivity, on lipoprotein metabolism in patients with T2DM. Pio treatment reduced TG levels by increasing the fractional clearance rate (FCR) of VLDL TGs from the circulation, without changing direct removal of VLDL particles. This indicated increased lipolysis of VLDL TGs during Pio treatment, a mechanism supported by our finding of increased plasma LPL mass and decreased levels of plasma apoC-III. Lower apoC-III levels were due to reduced apoC-III PRs. We saw no effects of Pio on the PR of either VLDL TG or VLDL apoB. Thus, Pio, a PPARgamma agonist, reduced VLDL TG levels by increasing LPL mass and inhibiting apoC-III PR. These 2 changes were associated with an increased FCR of VLDL TGs, almost certainly due to increased LPL-mediated lipolysis.
Nagashima
Kazunori
K
Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA.
Lopez
Carlos
C
Donovan
Daniel
D
Ngai
Colleen
C
Fontanez
Nelson
N
Bensadoun
André
A
Fruchart-Najib
Jamila
J
Holleran
Steve
S
Cohn
Jeffrey S
JS
Ramakrishnan
Rajasekhar
R
Ginsberg
Henry N
HN
D052242:Adiponectin; D000328:Adult; D000368:Aged; D001786:Blood Glucose; D008076:Cholesterol, HDL / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D005227:Fatty Acids / Q000097:blood; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007328:Insulin / Q000097:blood; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood; D008074:Lipoproteins / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D047495:PPAR gamma / Q000819:agonists*; D000077205:Pioglitazone; D045162:Thiazolidinediones / Q000494:pharmacology*; D014280:Triglycerides / Q000097:blood
D052242:Adiponectin; D001786:Blood Glucose; D008076:Cholesterol, HDL; D005227:Fatty Acids; D007004:Hypoglycemic Agents; D007328:Insulin; D036341:Intercellular Signaling Peptides and Proteins; D008074:Lipoproteins; D047495:PPAR gamma; D045162:Thiazolidinediones; D014280:Triglycerides; D000077205:Pioglitazone