Glucose-induced islet hyperemia is mediated by nitric oxide

Purpose To determine whether hyperglycemia affects pancreatic islet microcirculation in vivo and whether nitric oxide is a mediator. Methods Islet blood flow was measured before and after infusion of glucose during in vivo microscopy of mouse pancreatic islet. The pancreas of male BALB/c mice was exteriorized and viewed under the microscope utilizing monochromatic transmitted light. The carotid artery and tail vein were cannulated and systemic blood pressure was monitored continuously. Under fluorescent light, a 0.02 mL bolus of 2% fluorescein isothyocyanate (FITC-albumin) was injected intra-arterially and the first pulse of FITC-albumin through an islet capillary was videorecorded. Following equilibration, either glucose or normal saline 300 mg/g of body weight was given Intravenously. Five minutes later, a second bolus was given and the second pulse was videorecorded. The study was repeated in the presence of Nω-ni-tro-l-arginine methyl ester (l-NAME). The FITC-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 significant increase in islet blood flow with no change in systemic blood pressure: baseline TT was 20 ±1.3 pixel/0.03 sec and baseline OCT was 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 basal via paired t-test). Continuous infusion of l-NAME negated the effect of hyperglycemia on islet blood flow: baseline TT was 20 ± 1.8 pixel/0.03 sec and OCT was and 0.6 ± 0.05 seconds; during hyperglycemia, 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 These data suggest that hyperglycemia results in Increased islet capillary flow and nitric oxide is a regulator of islet blood flow during in vivo microscopy of the mouse islet.