title: Effects of the PPARgamma agonist pioglitazone on lipoprotein metabolism in patients with type 2 diabetes mellitus.
abstract: 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.
authors.affiliation: Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA.
authors.forename: Kazunori
authors.initials: K
authors.lastname: Nagashima
authors.forename: Carlos
authors.initials: C
authors.lastname: Lopez
authors.forename: Daniel
authors.initials: D
authors.lastname: Donovan
authors.forename: Colleen
authors.initials: C
authors.lastname: Ngai
authors.forename: Nelson
authors.initials: N
authors.lastname: Fontanez
authors.forename: André
authors.initials: A
authors.lastname: Bensadoun
authors.forename: Jamila
authors.initials: J
authors.lastname: Fruchart-Najib
authors.forename: Steve
authors.initials: S
authors.lastname: Holleran
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Cohn
authors.forename: Rajasekhar
authors.initials: R
authors.lastname: Ramakrishnan
authors.forename: Henry N
authors.initials: HN
authors.lastname: Ginsberg
mesh_terms: 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
chemical_list: 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