Dissociation between the insulin-sensitizing effect of rosiglitazone and its effect on hepatic and intestinal lipoprotein production.

Context: Despite its potent, well-documented insulin-sensitizing effects, rosiglitazone (RSG) does not effectively ameliorate the hypertriglyceridemia of insulin-resistant or diabetic individuals and has even been shown to slightly but significantly increase triglyceride-rich lipoproteins (TRL) in some studies. The mechanism of this effect is currently not known.

Objective: We investigated the effect of RSG treatment on TRL metabolism.

Enhancement of muscle glucose uptake by the vasopeptidase inhibitor, omapatrilat, is independent of insulin signaling and the AMP kinase pathway.

Omapatrilat (OMA), a vasopeptidase inhibitor (VPI), presently being tested in clinical trials for its antihypertensive properties, inhibits both angiotensin-converting enzyme and neutral endopeptidase, and raises tissue bradykinin levels. Recent studies from our laboratory and those of others have demonstrated that VPIs enhance muscle glucose uptake in animal models, and this effect is mediated by the bradykinin-nitric oxide pathway. The mechanism of the effect of OMA on muscle glucose uptake, however, is presently unknown.

Hyperinsulinemia is associated with increased production rate of intestinal apolipoprotein B-48-containing lipoproteins in humans.

Objective: Whereas postprandial hyperlipidemia is a well-described feature of insulin-resistant states and type 2 diabetes, no previous studies have examined intestinal lipoprotein production rates (PRs) in relation to hyperinsulinemia or insulin resistance in humans.

Methods And Results: Apolipoprotein B-48 (apoB-48)-containing lipoprotein metabolism was examined in the steady-state fed condition with a 15-hour primed constant infusion of [D3]-l-leucine in 14 nondiabetic men with a broad range of body mass index (BMI) and insulin sensitivity. To examine the relationship between indices of insulin resistance and intestinal lipoprotein PR data were analyzed in 2 ways: by correlation and by comparing apoB-48 PRs in those whose fasting plasma insulin concentrations were above or below the median for the 14 subjects studied (60 pmol/L).

Atorvastatin induces insulin sensitization in Zucker lean and fatty rats.

Background: The 3-hydroxy-3-methyl glutaryl coenzyme A (HMG-CoA) reductase inhibitors ('statins') have been implicated in preventing new onset type 2 diabetes, whereas the mechanism of this effect is not known. We investigated the effects of an HMG-CoA reductase inhibitor, atorvastatin, on insulin sensitization in Zucker lean and fatty rats.

Methods And Results: In vivo studies of insulin sensitization were performed in chow fed Zucker lean and fatty rats treated with atorvastatin 50mg/kg/day (ATORVA_50) and results were compared to Zucker lean and fatty rats treated with drug vehicle only (CONT).

Mechanism of highly active anti-retroviral therapy-induced hyperlipidemia in HIV-infected individuals.

The use of highly active anti-retroviral therapy (HAART) is associated with long-term adverse metabolic events including lipodystrophy, dyslipidemia, and insulin resistance. The purpose of the present study was to prospectively examine the mechanism of HAART-induced hyperlipidemia in HIV-seropositive, HAART-naive men prior to the development of frank lipodystrophy. Patient's (n = 13) weight, BMI, lean mass, and percent fat mass, waist circumference did not change after 8 weeks of treatment with HAART.