Effects of gemfibrozil on insulin resistance to fat metabolism in subjects with type 2 diabetes and hypertriglyceridaemia

Whitelaw, Donald; Smith, Janet; Nattrass, M.

doi:10.1046/j.1463-1326.2002.00199.x

Cited by 23 publications

(8 citation statements)

References 34 publications

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“…It is clinically important to determine how individuals with inherently different oxidative capacities tolerate stresses known to exacerbate the insulin-resistant condition, such as high-fat feeding. Previous studies have attempted to assess the causative role of diminished oxidative capacity on the development of insulin resistance by manipulating genes involved in lipid oxidation either directly (1,11,12,20,21,38,49,63) or pharmacologically (15,19,41,52,64,67,71), but efforts have yielded varying results. Additionally, current strategies such as chemical, physical, gene knockout, and mutagenic approaches fail to emulate mechanistically the progression of complex diseases and provide no direct information as to what combination of allelic variants is responsible for a given environment.…”

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confidence: 99%

Artificial selection for high-capacity endurance running is protective against high-fat diet-induced insulin resistance

Noland¹,

Thyfault²,

Henes³

et al. 2007

American Journal of Physiology-Endocrinology and Metabolism

122

138

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Dohm GL, Cortright RN, Lust RM. Artificial selection for high-capacity endurance running is protective against high-fat diet-induced insulin resistance. Am J Physiol Endocrinol Metab 293: E31-E41, 2007. First published March 6, 2007; doi:10.1152/ajpendo.00500.2006.-Elevated oxidative capacity, such as occurs via endurance exercise training, is believed to protect against the development of obesity and diabetes. Rats bred both for low (LCR)-and high (HCR)-capacity endurance running provide a genetic model with inherent differences in aerobic capacity that allows for the testing of this supposition without the confounding effects of a training stimulus. The purpose of this investigation was to determine the effects of a high-fat diet (HFD) on weight gain patterns, insulin sensitivity, and fatty acid oxidative capacity in LCR and HCR male rats in the untrained state. Results indicate chow-fed LCR rats were heavier, hypertriglyceridemic, less insulin sensitive, and had lower skeletal muscle oxidative capacity compared with HCR rats. Upon exposure to an HFD, LCR rats gained more weight and fat mass, and their insulin resistant condition was exacerbated, despite consuming similar amounts of metabolizable energy as chow-fed controls. These metabolic variables remained unaltered in HCR rats. The HFD increased skeletal muscle oxidative capacity similarly in both strains, whereas hepatic oxidative capacity was diminished only in LCR rats. These results suggest that LCR rats are predisposed to obesity and that expansion of skeletal muscle oxidative capacity does not prevent excess weight gain or the exacerbation of insulin resistance on an HFD. Elevated basal skeletal muscle oxidative capacity and the ability to preserve liver oxidative capacity may protect HCR rats from HFD-induced obesity and insulin resistance. fatty acid; lipid metabolism; liver; heart; skeletal muscle THE INCIDENCE OF METABOLIC DISEASES such as obesity and type II diabetes is increasing dramatically and is strongly linked to the rise in cardiovascular disease. In 2002, ϳ64% of the population in the United States was classified as overweight or obese (22), and health care costs attributable to these conditions exceeded $78 billion dollars (13). Although type II diabetes afflicts a substantially lower percentage (ϳ6.3%) of the population (9), this disease accounts for $132 billion in annual health care costs (24). With the increase in the incidence of such metabolic diseases reaching epidemic proportions and the threat of health care costs spiraling out of control, much research has been focused toward elucidating the mechanisms involved in the etiology of these conditions in hopes of ultimately discovering better treatments. Several therapies are currently used to alleviate symptoms of these diseases, but other than dietary modifications, endurance exercise is the only universally prescribed treatment.Enhanced aerobic capacity has long been associated with diminished morbidity and improvements in functional living, yet all the physiological mechanisms ...

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confidence: 99%

Artificial selection for high-capacity endurance running is protective against high-fat diet-induced insulin resistance

Noland¹,

Thyfault²,

Henes³

et al. 2007

American Journal of Physiology-Endocrinology and Metabolism

122

138

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“…Studies of the other fibrates (gemfibrozil, fenofibrate, ciprofibrate, and clofibrate) have not shown such effects (8–14), and these drugs are far more selective for PPAR-α than bezafibrate (15). Hence, it is reasonable to hypothesize that the status of bezafibrate as a pan-PPAR agonist may give it antidiabetic properties unique among fibrates.…”

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confidence: 99%

Antidiabetic Action of Bezafibrate in a Large Observational Database

et al. 2009

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OBJECTIVE -The purpose of this study was to test the hypothesis that bezafibrate, an approved fibrate, can prevent or delay type 2 diabetes.RESEARCH DESIGN AND METHODS -This was a retrospective cohort study using data from routine medical practice in the U.K., as captured by the General Practice Research Database (GPRD). Individuals chronically exposed to bezafibrate were compared with individuals chronically exposed to other fibrates. Hazard ratios (HRs) for incident type 2 diabetes were calculated using a Cox proportional hazards model. A post hoc analysis was used to examine the effect of bezafibrate on progression to use of oral antidiabetic medications or insulin in individuals with diabetes at baseline. CONCLUSIONS -Bezafibrate appears to have clinically important antidiabetic properties. Randomized controlled trials should be considered to assess the utility of bezafibrate in treating patients with diabetes or in preventing diabetes in high-risk patients. RESULTS Diabetes Care 32:547-551, 2009

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“…Treatment with gemfibrozil in patients with phenotypes including type 2 diabetes, dyslipidemia with glucose intolerance, and hypertriglyceridemia with normal glucose tolerance has been reported to improve insulin sensitivity (4,20), have no effect on insulin sensitivity (10,33), or have beneficial effects in subsets of patients on the basis of glycemia (25). Treatment with fenofibrate enhances insulin sensitivity in dyslipidemic patients with normal glucose metabolism (36) but has no effect on insulin responses in subjects with metabolic syndrome (32).…”

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confidence: 99%

PPARα activation elevates blood pressure and does not correct glucocorticoid-induced insulin resistance in humans

Subramanian¹,

DeRosa²,

Bernal‐Mizrachi³

et al. 2006

American Journal of Physiology-Endocrinology and Metabolism

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Effects of gemfibrozil on insulin resistance to fat metabolism in subjects with type 2 diabetes and hypertriglyceridaemia

Abstract: Gemfibrozil does not affect insulin sensitivity to glucose or fat metabolism in type 2 diabetes but enhances the lowering of plasma NEFA concentrations by insulin, probably by reducing hepatic fatty acid synthesis.

Cited by 23 publications

References 34 publications

Artificial selection for high-capacity endurance running is protective against high-fat diet-induced insulin resistance

Artificial selection for high-capacity endurance running is protective against high-fat diet-induced insulin resistance

Antidiabetic Action of Bezafibrate in a Large Observational Database

PPARα activation elevates blood pressure and does not correct glucocorticoid-induced insulin resistance in humans

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