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To assess the effects of aging on glucose tolerance and insulin action, euglycemic (5 mg/dl) hyperinsulinemic (300 microU/min) clamps were performed for 1 hour in lean, middle-aged (26 months), and old (32 months) Fischer 344 rats. Glucose, insulin, and counterregulatory hormone concentrations were measured at baseline and during clamping. Insulin-mediated glucose uptake (micromol.kg-1.min-1) was reduced to 12.0 +/- 1.0, 10.2 +/- 2.1, and 7.6 +/- 1.1 in old compared with lean rats (P less than 0.05). The mean steady-state glucose concentrations (micromol.L-1) during clamping were significantly elevated in old (P less than 0.05) compared with lean and middle-aged rats (119 +/- 3 and 108 +/- 2). The two age groups did not differ in their counterregulatory hormone response, which was similar in magnitude to that observed in obese Zucker rats. The percent decrease in free fatty acids from baseline during clamping was significantly less in middle-aged compared with lean rats (P less than 0.05). These results indicate that middle-aged and old Fischer 344 rats have impaired glucose tolerance and insulin action. In contrast to the pronounced glucose intolerance of obese Zucker rats, the age-related deterioration in glucose tolerance in Fischer 344 rats is not accompanied by a change in the insulin-mediated glucose disposal.Project Summary/Abstract Conventional anti-HIV drugs disrupt the fusion process between HIV-1 and target cells by binding to the virus and changing the conformation of gp41, which renders the fusion machinery incapable of efficiently fusing the virus to the host membrane. The reliance on specific HIV-1 envelope (Env) glycoproteins to target its fusion machinery to the host cell has required the development of neutralizing antibodies to Env, which exhibit a broad neutralizing activity against diverse HIV-1 clades. However, the production of such anti-Env Abs remains challenging, and the potential for HIV-1 resistance
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