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Effects of the PPARγ agonist pioglitazone on lipoprotein metabolism in patients with type 2 diabetes mellitus
Kazunori Nagashima, … , Rajasekhar Ramakrishnan, Henry N. Ginsberg
Kazunori Nagashima, … , Rajasekhar Ramakrishnan, Henry N. Ginsberg
Published May 2, 2005
Citation Information: J Clin Invest. 2005;115(5):1323-1332. https://doi.org/10.1172/JCI23219.
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Article Metabolism

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

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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.

Authors

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

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Figure 1

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Mean levels ± SD of fasting glucose (A), insulin (B), FAs (C), and adipo...
Mean levels ± SD of fasting glucose (A), insulin (B), FAs (C), and adiponectin (D) in patients during placebo (black bars) and Pio (white bars) treatments. The placebo values are single fasting blood samples obtained at the start of placebo treatment, while the Pio values are the means of 2 fasting blood samples obtained at the last 2 outpatient visits during treatment (either weeks 12 and 13 or weeks 12 and 15). Pio treatment was associated with reductions in plasma glucose, insulin, and FA levels, while adiponectin levels increased during Pio treatment.

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ISSN: 0021-9738 (print), 1558-8238 (online)

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