Abstract
The aim of this study was to compare the effects of glimepiride and glibenclamide on tumour necrosis factor (TNF)-alpha expression and adipocyte cellularity in spontaneously diabetic, obese rats. Eight-week-old male Otsuka Long-Evans Tokushima Fatty (OLETF) rats were randomized to receive glimepiride, glibenclamide or control treatment for 12 weeks, after which TNF-alpha mRNA levels, adipose tissue cellularity and physiological parameters were measured. TNF-alpha mRNA expression in retroperitoneal fat tissue was significantly greater in the glibenclamide group (2.2 +/- 1.1), compared with the control group (0.9 +/- 0.4; p<0.05) or the glimepiride group (0.9 +/- 0.2; p<0.01). The mean fat-cell area in retroperitoneal fat tissue was increased at study endpoint in the glibenclamide group (13,764 +/- 7036 microm2), compared with both the control and glimepiride groups (10,755 +/- 6193 microm2 and 11,317 +/- 5646 microm2 respectively; p<0.05). Investigation of cellularity revealed a decrease in the frequency of small fat cells and an increase in the frequency of large fat cells in both the glibenclamide and glimepiride groups compared with the control group, with a greater increase in large fat cells in the glibenclamide group. At study endpoint, insulin and triglyceride values were significantly higher in the active treatment groups compared with the control group; however, insulin levels were significantly greater in glibenclamide-treated animals compared with glimepiride-treated animals. An oral glucose tolerance test performed at the end of the study showed that there were no significant differences among the three groups in terms of plasma glucose and insulin concentrations. This study suggests that although both glibenclamide and glimepiride may have a hypertrophisizing effect on fat cells in adipose tissues, this effect is greater with glibenclamide, leading to augmentation of TNF-alpha mRNA expression and possible exacerbation of insulin resistance.
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