Effects of the PPARγ agonist pioglitazone on lipoprotein metabolism in patients with type 2 diabetes mellitus

Kazunori Nagashima, Carlos Lopez, Daniel Donovan, Colleen Ngai, Nelson Fontanez, André Bensadoun, Jamila Fruchart-Najib, Steve Holleran, Jeffrey S. Cohn, Rajasekhar Ramakrishnan, Henry N. Ginsberg

Research output: Contribution to journalArticlepeer-review

178 Scopus citations

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 PPARγ 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 PPARγ 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.

Original languageEnglish
Pages (from-to)1323-1332
Number of pages10
JournalJournal of Clinical Investigation
Volume115
Issue number5
DOIs
StatePublished - May 2005
Externally publishedYes

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