Diabetes in the Goto-Kakizaki rat is accompanied by impaired insulin-mediated myosin-bound phosphatase activation and vascular smooth muscle cell relaxation.

Abstract

Our laboratory has demonstrated that insulin rapidly stimulates myosin-bound phosphatase (MBP) activity in vascular smooth muscle cells (VSMCs). In this study, we examined whether diabetes is accompanied by alterations in MBP activation and elucidated the components of the signaling pathway that mediate the effects of diabetes. VSMCs isolated from Goto-Kakizaki (GK) diabetic rats (a model for type 2 diabetes) exhibited marked impairment in MBP activation by insulin that was accompanied by failure of insulin to decrease the phosphorylation of a regulatory myosin-bound subunit (

Fasudil hydrochloride induces osteoblastic differentiation of stromal cell lines, C3H10T1/2 and ST2, via bone morphogenetic protein-2 expression

“…At a molecular level, ROK upregulates various molecules that accelerate inflammation/ oxidative stress and fibrosis, whereas it downregulates NOS. ROK activity is increased in animals with experimental atherosclerosis [11,12], hypertension [13], and diabetes [14]. Furthermore, risk factors for atherosclerosis including oxidized LDL [15], hyperglycemia [16], and nicotine [17] increase Rho/ROK activity.…”

Elevated L-PGDS activity contributes to PMA-induced apoptosis concomitant with downregulation of PI3-K

“…Anti-p110 and anti-p85 antibodies were used to immunoprecipitate PI3-K activity from 500 g of precleared lysate. Assays were performed as previously described (20).…”

The PI3-K/Akt pathway: roles related to alterations in vasomotor responses in diabetic models

“…Although an accumulating body of evidence indicates that endothelium-dependent relaxation is weaker both in a type I diabetic model, namely the streptozotocin (STZ)-induced rat (Oyama et al, 1986;Kamata et al, 1989aKamata et al, , b, 1996aKamata et al, ,b,c, 1997Abiru et al, 1990a, b;Miyata et al, 1992a,b;Tomlinson et al, 1992;Poston and Taylor, 1995;Pieper, 1998;De Vriese et al, 2000;Makino et al, 2000Makino et al, , 2002Matsumoto et al, 2003Matsumoto et al, , 2004Kobayashi et al, 2004c), and in type II diabetic rats (Sakamoto et al, 1998;Walker et al, 1999;Kagota et al, 2000;Sandu et al, 2000;Kim et al, 2002;Witte et al, 2002;Matsumoto et al, 2004;Kobayashi et al, 2004c), we and others have noted an augmented or unaltered endothelium-dependent relaxation at an early stage in STZdiabetes (Brands and Fitzgerald, 1998;Pieper, 1999, Kobayashi and Kamata, 1999a, Kobayashi et al, 2005b. Moreover, there is some clinical and experimental evidence of augmented blood flow at early stages of diabetes (Jaap and Tooke, 1995;Cipolla et al, 1996; Abbreviations: ACh, acetylcholine; Ang II, angiotensin II; L-Arg, L-arginine; BH4, tetrahydrobiopterin; DOCA, deoxycorticosterone acetate; eNOS, endothelial NO synthase; ET-1, endothelin-1; GSK, glycogen synthase kinase; HDL, high density lipoprotein; HSP, heat-shock protein; IGF-1, insulin-like growth factor 1; IP3, inositol 1,4,5,-triphosphate; IRS-1, insulin receptor substrate-1; LDL, low density lipoprotein; NE, norepinephrine; NO, nitric oxide; NOS, NO synthase; PDK, PI-dependent kinase; PI3-K, phosphatidylinositol 3-kinase; PIP3, phosphatidylinositol-3,4,5-trisphosphate; PTEN, phosphatase and tensin homolog; STZ, streptozotocin; VEGF, vascular endothelial growth factor.…”