TY - JOUR
T1 - Effects of the PPARγ agonist pioglitazone on lipoprotein metabolism in patients with type 2 diabetes mellitus
AU - Nagashima, Kazunori
AU - Lopez, Carlos
AU - Donovan, Daniel
AU - Ngai, Colleen
AU - Fontanez, Nelson
AU - Bensadoun, André
AU - Fruchart-Najib, Jamila
AU - Holleran, Steve
AU - Cohn, Jeffrey S.
AU - Ramakrishnan, Rajasekhar
AU - Ginsberg, Henry N.
PY - 2005/5
Y1 - 2005/5
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=20944439286&partnerID=8YFLogxK
U2 - 10.1172/JCI200523219
DO - 10.1172/JCI200523219
M3 - Article
C2 - 15841215
AN - SCOPUS:20944439286
SN - 0021-9738
VL - 115
SP - 1323
EP - 1332
JO - Journal of Clinical Investigation
JF - Journal of Clinical Investigation
IS - 5
ER -