Vasoactive drugs enhance pancreatic islet blood flow, augment insulin secretion and improve glucose tolerance in female rats
Résumé
Pravastatin, irbesartan and captopril are frequently used in the treatment of patients with type 2 diabetes. These drugs are also exerting beneficial metabolic effects, causing an improved glucose tolerance in the patients but the precise nature of the mechanisms by which this is achieved remains elusive. To this end, we have now studied whether these drugs influence insulin secretion in vivo through effects on islet blood perfusion. Captopril (3 mg/kg), irbesartan (3 mg/kg), pravastatin (0.5 mg/kg) were injected intravenously to anesthetized female Wistar rats. Blood flow rates were determined by a microsphere technique. Blood glucose concentrations were measured with test reagent strips and serum insulin concentrations with ELISA. Pancreatic blood flow was markedly increased by pravastatin (p<0.001), captopril (p<0.05) and irbesartan (p<0.01). Pancreatic islet blood flow was significantly and preferentially enhanced after the administration of captopril (p<0.01), irbesartan (p<0.01) and pravastatin (p<0.001). Renal blood flow was enhanced significantly, pravastatin (p<0.01), irbesartan (p<0.05), captopril (p<0.01). Captopril and pravastatin also enhanced late phase insulin secretion and positively influenced glycemia upon intraperitoneal glucose tolerance tests. In conclusion, the present study suggests that a local pancreatic RAS and pravastatin treatment may be selectively controlling pancreatic islet blood flow, augmenting insulin secretion and thereby improving glucose tolerance. Our findings indicate significant gender-related differences in the vascular response to these agents. Since statins and RAS inhibitors are frequently used by diabetic patients, the antidiabetic actions of these drugs previously reported might in part occur through the beneficial direct islet effects shown here.
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