Glucose-induced islet hyperemia is mediated by nitric oxide.
OBJECTIVE
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 N omega-nitro-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).
Moldovan
S
S
Department of Surgery, Veterans Affairs Medical Center-West Los Angeles, California, USA.
Livingston
E
E
Zhang
R S
RS
Kleinman
R
R
Guth
P
P
Brunicardi
F C
FC
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001794:Blood Pressure; D005947:Glucose / Q000008:administration & dosage; D006943:Hyperglycemia / Q000503:physiopathology*; D007515:Islets of Langerhans / Q000098:blood supply*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008833:Microcirculation; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors
D009569:Nitric Oxide; D001120:Arginine; D019001:Nitric Oxide Synthase; D005947:Glucose; D019331:NG-Nitroarginine Methyl Ester