Multiple mechanisms of early hyperglycaemic injury of the rat intestinal microcirculation

Clinical and Experimental Pharmacology & Physiology
H Glenn BohlenJong Shiaw Jin

Abstract

1. Hyperglycaemia in the vast majority of humans with diabetes mellitus is the end result of profound insulin resistance secondary to obesity. For patients in treatment, hyperglycaemia is usually not sustained but, rather, occurs intermittently. In in vivo studies of the rat intestinal microcirculation, endothelial impairment occurs within 30 min at D-glucose concentrations > or = 300 mg/dL. Endothelial-dependent dilation to acetylcholine and constriction to noradrenaline is impaired. Vasodilation to exogenous nitric oxide (NO) remains normal. 2. When initiated before hyperglycaemia, suppression of oxygen radicals by both scavenging and pretreatment with cyclo-oxygenase blockade to prevent oxygen radical formation minimized endothelial impairments during hyperglycaemia. Neither treatment was effective in restoring endothelial function once it was damaged by hyperglycaemia. 3. A mechanism that may initiate the arachidonic acid- oxygen radical process is activation of specific isoforms of protein kinase C (PKC). De novo formation of diacylglycerol during hyperglycaemia activates PKC. Blockade of the beta II PKC isoform with LY-333531 prior to hyperglycaemia protected NO formation within the arteriolar wall, as judged with NO-sens...Continue Reading

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Citations

Sep 11, 2014·Fibrogenesis & Tissue Repair·Swayam Prakash SrivastavaKeizo Kanasaki
Feb 20, 2004·Current Hypertension Reports·H Glenn Bohlen
Jan 8, 2005·Journal of Vascular Research·A ColantuoniP L Marchiafava
Oct 24, 2007·Surgery·El Rasheid ZakariaRichard N Garrison
Aug 19, 2007·Diabetes, Obesity & Metabolism·R E KlabundeC E Paxson
Oct 4, 2006·Nephrology·Jun Li, Glenda Gobe
Nov 28, 2013·Journal of Vascular Research·Ines Drenjancevic, Aleksandar Kibel
Aug 15, 2006·American Journal of Physiology. Heart and Circulatory Physiology·Lusha XiangRobert L Hester
Aug 16, 2003·American Journal of Physiology. Heart and Circulatory Physiology·M M TickerhoofD H Korzick
Nov 14, 2002·International Journal of Pharmaceutics·S Le Lamer-DéchampsF Bressolle

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