Gene interactions and pathways from curated databases and text-mining
Kidney Int 2011, PMID: 21228767

Glomerular-specific protein kinase C-β-induced insulin receptor substrate-1 dysfunction and insulin resistance in rat models of diabetes and obesity.

Mima, Akira; Ohshiro, Yuzuru; Kitada, Munehiro; Matsumoto, Motonobu; Geraldes, Pedro; Li, Chenzhong; Li, Qian; White, Gregory S; Cahill, Christopher; Rask-Madsen, Christian; King, George L

Insulin resistance has been associated with the progression of chronic kidney disease in both diabetes and obesity. In order to determine the cellular mechanisms contributing to this, we characterized insulin signaling in renal tubules and glomeruli during diabetic and insulin-resistant states using streptozotocin-diabetic and Zucker fatty-insulin-resistant rats. Compared with nondiabetic and Zucker lean rats, the insulin-induced phosphorylation of insulin receptor substrate-1 (IRS1), Akt, endothelial nitric oxide synthase, and glycogen synthase kinase 3α were selectively inhibited in the glomeruli but not in the renal tubules of both respective models. Protein, but not mRNA levels of IRS1, was decreased only in the glomeruli of streptozotocin-diabetic rats likely due to increased ubiquitination. Treatment with the protein kinase C-β inhibitor, ruboxistaurin, enhanced insulin actions and elevated IRS1 expression. In glomerular endothelial cells, high glucose inhibited the phosphorylation of Akt, endothelial nitric oxide synthase, and glycogen synthase kinase 3α; decreased IRS1 protein expression and increased its association with ubiquitin. Overexpression of IRS1 or the addition of ruboxistaurin reversed the inhibitory effects of high glucose. Thus, loss of insulin's effect on endothelial nitric oxide synthase and glycogen synthase kinase 3α activation may contribute to the glomerulopathy observed in diabetes and obesity.

Diseases/Pathways annotated by Medline MESH: Diabetes Mellitus, Experimental, Insulin Resistance, Obesity
Document information provided by NCBI PubMed

Text Mining Data

Akt → insulin: " Compared with nondiabetic and Zucker lean rats, the insulin induced phosphorylation of insulin receptor substrate-1 (IRS1), Akt , endothelial nitric oxide synthase, and glycogen synthase kinase 3a were selectively inhibited in the glomeruli but not in the renal tubules of both respective models "

insulin receptor substrate-1 (IRS1) → insulin: " Compared with nondiabetic and Zucker lean rats, the insulin induced phosphorylation of insulin receptor substrate-1 (IRS1) , Akt, endothelial nitric oxide synthase, and glycogen synthase kinase 3a were selectively inhibited in the glomeruli but not in the renal tubules of both respective models "

nitric oxide synthase → insulin: " Compared with nondiabetic and Zucker lean rats, the insulin induced phosphorylation of insulin receptor substrate-1 (IRS1), Akt, endothelial nitric oxide synthase , and glycogen synthase kinase 3a were selectively inhibited in the glomeruli but not in the renal tubules of both respective models "

nitric oxide synthase — insulin: " Thus, loss of insulin 's effect on endothelial nitric oxide synthase and glycogen synthase kinase 3a activation may contribute to the glomerulopathy observed in diabetes and obesity "

Manually curated Databases

No curated data.