Vasoactive drugs enhance pancreatic islet blood flow, augment insulin secretion and improve glucose tolerance in female rats.
Pravastatin, irbesartan and captopril are frequently used in the treatment of patients with Type 2 diabetes. These drugs also exert beneficial metabolic effects, causing an improved glucose tolerance in patients, but the precise mechanisms by which this is achieved remain elusive. To this end, we have studied whether these drugs influence insulin secretion in vivo through effects on islet blood perfusion. Captopril (3 mg/kg of body weight), irbesartan (3 mg/kg of body weight) and pravastatin (0.5 mg/kg of body weight) were injected intravenously into anaesthetized 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 were measured by 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). Kidney blood flow was enhanced significantly by pravastatin (P<0.01), irbesartan (P<0.05) and captopril (P<0.01). Captopril and pravastatin also enhanced late-phase insulin secretion and positively influenced glycaemia in intraperitoneal glucose tolerance tests. In conclusion, the present study suggests that a local pancreatic renin-angiotensin system 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 renin-angiotensin system inhibitors are frequently used by diabetic patients, the antidiabetic actions of these drugs reported previously might occur, in part, through the beneficial direct islet effects shown in the present study.
Huang
Zhen
Z
Department of Internal Medicine, Karolinska Institutet, Stockholm South Hospital, SE 118 83 Stockholm, Sweden.
Jansson
Leif
L
Sjöholm
Ake
A
D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D001713:Biphenyl Compounds / Q000494:pharmacology; D001786:Blood Glucose / Q000032:analysis; D002216:Captopril / Q000494:pharmacology; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy; D005260:Female; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology; D007328:Insulin / Q000097:blood; D000077405:Irbesartan; D007515:Islets of Langerhans / Q000098:blood supply*; D010179:Pancreas / Q000098:blood supply*; D017035:Pravastatin / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012039:Regional Blood Flow / Q000187:drug effects; D012737:Sex Factors; D013777:Tetrazoles / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology*
D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D001713:Biphenyl Compounds; D001786:Blood Glucose; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007328:Insulin; D013777:Tetrazoles; D014665:Vasodilator Agents; D002216:Captopril; D000077405:Irbesartan; D017035:Pravastatin