Gender-specific regulation of pancreatic islet blood flow, insulin levels, and glycemia in spontaneously diabetic Goto-Kakizaki rats
Résumé
Diabetic patients are often treated with a statin against hyperlipidemia and an ACE inhibitor or angiotensin receptor antagonist against hypertension or albuminuria. These drugs may also exert beneficial metabolic effects, causing an improved glucose tolerance in patients. Gender-related differences have also been observed in the clinical responsiveness to these drugs, but the mechanism behind this is unclear. We now studied whether these drugs and the fatty acid palmitate influence pancreatic microcirculation, thereby impacting insulin secretion and glycemia in vivo, in spontaneously diabetic male and female Goto-Kakizaki rats. In male rats, islet blood flow (IBF) and total pancreatic blood flow (PBF) were increased significantly by pravastatin, captopril and irbesartan. Serum insulin levels were increased by pravastatin and captopril. Palmitate suppressed IBF and raised blood glucose. In female animals, IBF was stimulated by captopril, candesartan and irbesartan. PBF was increased by captopril, candesartan and irbesartan, and by pravastatin. Palmitate suppressed IBF and serum insulin secretion. In conclusion, the present study lends support to the view that a local pancreatic RAS and pravastatin may be selectively influencing pancreatic microcirculation and therefore affecting insulin secretion and glycemia. Free fatty acids impaired islet blood flow, suppressed insulin secretion, and raised blood glucose. Substantial gender-related differences in the vascular and metabolic responses to these drugs prevail in this diabetic animal model.
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