Title : High glucose and insulin inhibit VSMC MKP-1 expression by blocking iNOS via p38 MAPK activation.

Pub. Date : 2000 Jan

PMID : 10644515






6 Functional Relationships(s)
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1 High glucose and insulin inhibit VSMC MKP-1 expression by blocking iNOS via p38 MAPK activation. Glucose nitric oxide synthase 2 Rattus norvegicus
2 To understand the mechanism of insulin resistance induced by high glucose and insulin, we studied the regulation of iNOS protein induction in these cells. Glucose nitric oxide synthase 2 Rattus norvegicus
3 Both high glucose and chronic insulin treatment caused a marked impairment of iNOS induction in response to acute insulin. Glucose nitric oxide synthase 2 Rattus norvegicus
4 Blocking of signaling via the p38 mitogen-activated protein kinase (MAPK) pathway by prior treatment for 1 h with SB-203580, a synthetic p38 MAPK inhibitor, completely prevented the inhibition of iNOS induced by high glucose and insulin and restored MKP-1 induction to levels observed with acute insulin treatment. Glucose nitric oxide synthase 2 Rattus norvegicus
5 We conclude 1) that chronic insulin and high glucose-induced insulin resistance is accompanied by marked reductions in both iNOS and MKP-1 inductions due to p38 MAPK activation that leads to excessive cell growth and 2) that p38 MAPK/extracellular signal-regulated kinase pathways regulate iNOS induction, thereby controlling MKP-1 expression, which in turn inactivates MAPKs as a feedback mechanism and inhibits cell growth. Glucose nitric oxide synthase 2 Rattus norvegicus
6 We conclude 1) that chronic insulin and high glucose-induced insulin resistance is accompanied by marked reductions in both iNOS and MKP-1 inductions due to p38 MAPK activation that leads to excessive cell growth and 2) that p38 MAPK/extracellular signal-regulated kinase pathways regulate iNOS induction, thereby controlling MKP-1 expression, which in turn inactivates MAPKs as a feedback mechanism and inhibits cell growth. Glucose nitric oxide synthase 2 Rattus norvegicus