GLUCOSE-INDUCED ISLET HYPEREMIA IS MEDIATED BY NITRIC-OXIDE

PURPOSE: TO determine whether hyperglycemia affects pancreatic islet m icrocirculation in vivo and whether nitric oxide is a mediator. METHOD S: Islet blood flow was measured before and after infusion of glucose during in vivo microscopy of mouse pancreatic islet. The pancreas of m ale BALB/c mice was exteriorized and viewed under the microscope utili zing monochromatic transmitted light. The carotid artery and tail vein were cannulated and systemic blood pressure was monitored continuousl y. Under fluorescent light, a 0.02 mt bolus of 2% fluorescein isothyoc yanate (FITC-albumin) was injected intra-arterially and the first puls e of FITC-albumin through an islet capillary was videorecorded. Follow ing equilibration, either glucose or normal saline 300 mg/g of body we ight was given intravenously. Five minutes later, a second bolus was g iven and the second pulse was videorecorded. The study was repeated in the presence of N omega-nitro-L-arginine methyl ester (L-NAME). The F ITC-albumin bolus mean transit time (TT) and observed cross time (OCT) through the islet were calculated using slow-motion video analysis of the recorded images. RESULTS: Infusion of glucose resulted in a signi ficant increase in islet blood flow with no change in systemic blood p ressure: baseline TT was 20 +/- 1.3 pixel/0.03 sec and baseline OCT wa s 0.6 +/- 0.04 seconds; during hyperglycemia, TT was 16.1 +/- 1 pixel/ 0.03 sec, and OCT was 0.48 +/- 0.03 seconds (n = 11, P <0.05 versus ba sal via paired t-test). Continuous infusion of L-NAME negated the effe ct of hyperglycemia on islet blood flow: baseline TT was 20 +/- 1.8 pi xel/0.03 sec and OCT was and 0.6 +/- 0.05 seconds; during hyperglycemi a, TT was 20 +/- 1.1 pixel/0.03 sec and OCT was 0.6 +/- 0.33 seconds ( n = 10; P <0.05 versus glucose via unpaired t-test). CONCLUSIONS: Thes e data suggest that hyperglycemia results in increased islet capillary flow and nitric oxide is a regulator of islet blood flow during in vi vo microscopy of the mouse islet.