Effects of gemfibrozil on insulin sensitivity and on haemostatic variables in hypertriglyceridemic patients

Mussoni, L.; Mannucci, L.; Sirtori, Cesare R.; Pazzucconi, Franco; Bonfardeci, Giuseppe; Cimminiello, Claudio; Notarbartoló, A; Scafidi, V.; Bon, Gabriele Bittolo; Alessandrini, Paola; Nenci, Giuseppe G.; Parise, P; Colombo, Luigi; Piliego, T.; Tremoli, Elena

doi:10.1016/s0021-9150(99)00283-x

Cited by 46 publications

(20 citation statements)

References 58 publications

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“…In control mice, however, gemfibrozil treatment resulted in a reduction in GHb and insulin levels. Both animal [54,55] and clinical studies [56] have reported an insulin-sensitising effect of fibrate therapy, which they attribute to a reduction in lipids. Moreover, Ide and co-workers demonstrated that fibrates can regulate the insulin receptor signalling pathway [57].…”

Section: Discussionmentioning

confidence: 99%

Gemfibrozil decreases atherosclerosis in experimental diabetes in association with a reduction in oxidative stress and inflammation

et al. 2006

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Section: Discussionmentioning

confidence: 99%

Gemfibrozil decreases atherosclerosis in experimental diabetes in association with a reduction in oxidative stress and inflammation

et al. 2006

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“…These data taken together suggest that lowering muscle lipid accumulation might be a key factor for an improvement of insulin sensitivity in humans with PPAR-␣ activators. Although still controversial, some recent clinical studies have shown improved insulin sensitivity by fibrates (12,13). The controversy over the consequence of PPAR-␣-induced lipid lowering in humans may be resolved by using a hyperinsulinemic-euglycemic clamp technique together with muscle lipid measurement.…”

Section: The Role Of Lipids In Ppar's Action On Insulin Sensitivitymentioning

confidence: 99%

“…Given that lipid oversupply/accumulation leads to insulin resistance, one would expect that lowering lipids with a PPAR-␣ agonist should also attenuate insulin resistance, as does a PPAR-␥ agonist in insulin-resistant states caused by lipid oversupply/accumulation (7). However, studies in humans have been inconclusive, with reports showing both improved (12,13) and unimproved insulin sensitivity (14,15). It might be that the PPAR-␣ agonists, though lowering circulating lipids, have little effect on muscle lipids in those reports in which insulin sensitivity is not improved.…”

mentioning

confidence: 99%

Peroxisome Proliferator—Activated Receptor (PPAR)-αActivation Lowers Muscle Lipids and Improves Insulin Sensitivity in High Fat—Fed Rats

et al. 2001

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Peroxisome proliferator-activated receptor (PPAR)-␣ agonists lower circulating lipids, but the consequences for muscle lipid metabolism and insulin sensitivity are not clear. We investigated whether PPAR-␣ activation improves insulin sensitivity in insulin-resistant rats and compared the effects with PPAR-␥ activation. Threeweek high fat-fed male Wistar rats were untreated or treated with the specific PPAR-␣ agonist WY14643 or the PPAR-␥ agonist pioglitazone (both 3 mg · kg -1 · day -1 ) for the last 2 weeks of high-fat feeding. Like pioglitazone, WY14643 lowered basal plasma levels of glucose, triglycerides (-16% vs. untreated), and leptin (-52%), and also muscle triglyceride (-34%) and total long-chain acyl-CoAs (LCACoAs) (-41%) (P < 0.05). In contrast to pioglitazone, WY14643 substantially reduced visceral fat weight and total liver triglyceride content (P < 0.01) without increasing body weight gain. WY14643 and pioglitazone similarly enhanced wholebody insulin sensitivity (clamp glucose infusion rate increased 35 and 37% and glucose disposal 22 and 15%, respectively, vs. untreated). Both agents enhanced insulin-mediated muscle glucose metabolic index (Rg') and reduced muscle triglyceride and LCACoA accumulation (P < 0.05). Although pioglitazone had more potent effects than WY14643 on muscle insulin sensitization, this was associated with its greater effect to reduce muscle LCACoA accumulation. Overall insulinmediated muscle Rg' was inversely correlated with the content of LCACoAs (r = -0.74, P = 0.001) and with plasma triglyceride levels (r = -0.77, P < 0.001). We conclude that even though WY14643 and pioglitazone, representing PPAR-␣ and PPAR-␥ activation, respectively, may alter muscle lipid supply by different mechanisms, both significantly improve muscle insulin action in the high fat-fed rat model of insulin resistance, and this effect is proportional to the degree to which they reduce muscle lipid accumulation. Diabetes 50:411-417, 2001

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“…The lowering of FFAs through increased oxidation may well improve insulin sensitivity. Specific PPAR-␣ agonism can lower lipid levels in rats and improve insulin sensitivity (76,77), whereas studies of fibrates in humans have either reported improved (78,79) or unimproved (80,81) insulin sensitivity.…”

Section: Ppar-␣mentioning

confidence: 99%

Lipids and Glucose in Type 2 Diabetes

2004

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Effects of gemfibrozil on insulin sensitivity and on haemostatic variables in hypertriglyceridemic patients

Cited by 46 publications

References 58 publications

Gemfibrozil decreases atherosclerosis in experimental diabetes in association with a reduction in oxidative stress and inflammation

Gemfibrozil decreases atherosclerosis in experimental diabetes in association with a reduction in oxidative stress and inflammation

Peroxisome Proliferator—Activated Receptor (PPAR)-αActivation Lowers Muscle Lipids and Improves Insulin Sensitivity in High Fat—Fed Rats

Lipids and Glucose in Type 2 Diabetes

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