title: Dysfunction of aorta involves different patterns of intracellular signaling pathways in diabetic rats.
abstract: Rat models of insulin-dependent (streptozotocin-induced) and independent (Otsuka Long-Evans Tokushima Fatty (OLETF)) diabetes had sustained and transient increases in blood glucose levels. Over-contraction due to norepinephrine was seen exclusively in streptozotocin rat aorta. Contraction was enhanced under high-glucose conditions in OLETF rats. In order to understand the association between these patterns of changes, total diacylglycerol was measured as a key element of phosphatidylinositol-turnover due to the conversion of some incorporated glucose into diacylglycerol. Streptozotocin rats had enhanced basal diacylglycerol. Both diacylglycerol kinase (metabolic enzyme of diacylglycerol) and total phosphatidylinositol turnover activities also increased on norepinephrine stimulation, independent of extracellular glucose level. On the other hand, diacylglycerol, diacylglycerol kinase and phosphatidylinositol turnover in OLETF rats increased under high glucose conditions in the absence of norepinephrine treatment. These results indicated that diacylglycerol and diacylglycerol kinase-mediated phosphatidylinositol turnover acceleration was influenced by an increase in glucose levels in OLETF rats or by receptor-mediated signals in streptozotocin rats including glucose desensitization based on submaximal incorporation. We suggest that the alteration of vascular dysfunction is induced by different factors in each type of diabetes.
authors.affiliation: Department of Pharmacology, School of Pharmaceutical Sciences, Showa University, 1-5-8 Hatanodai, Tokyo 142-8555, Shinagawa, Japan. kojinobe@pharm.showa-u.ac.jp
authors.forename: Koji
authors.initials: K
authors.lastname: Nobe
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Sakai
authors.forename: Hiromi
authors.initials: H
authors.lastname: Nobe
authors.forename: Kazutaka
authors.initials: K
authors.lastname: Momose
mesh_terms: D000818:Animals; D001011:Aorta / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D066298:In Vitro Techniques; D007424:Intracellular Fluid / Q000378:metabolism*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000502:physiology*; D014652:Vascular Diseases / Q000378:metabolism*