Regulation of the inducible nitric oxide synthase and sodium pump in type 1 diabetes.
Insulin-like growth factor-1 (IGF-1) is a hormone and growth factor closely related to insulin. The autocrine/paracrine actions of IGF-1 involve activation of inducible nitric oxide synthase (iNOS) and the Na(+), K(+)-ATPase sodium pump in cardiovascular tissues. Data from literature indicate that iNOS is expressed in vascular smooth muscle cells (VSMC) and that IGF-1-induced release of NO is both rapid and delayed. We hypothesize that impaired IGF-1-induced sodium pump activity/expression in rats with type 1 diabetes is related to activation of phosphatidylinositol 3 kinase (PI3K)/cytosolic phospholipase 2 (cPLA(2))/protein kinase B (Akt) signaling, and that IGF-1 prevents acute and chronic dysfunction of iNOS and sodium pump activity in a chemically induced model of type 1 diabetes, the streptozotocin-treated rat heart (STZ). Understanding how iNOS and sodium pump activity are regulated by IGF-1 activation of the PI3K/cPLA(2)/Akt cascade should provide novel and fundamental knowledge regarding the regulatory actions of IGF-1 in promoting vasodilation. Since insulin resistance is currently a major focus of research, the use of IGF-1 to improve insulin resistance and glucose metabolism has opened a new arena for treatment of comorbid conditions. Future investigations should now focus on mechanisms of action of IGF-1 and its clinical applicability.
Zakula
Zorica
Z
Institute Vinca, Laboratory for Molecular Genetics and Radiobiology, 11000 Belgrade, Serbia and Montenegro.
Koricanac
Goran
G
Putnikovic
Biljana
B
Markovic
Ljiljana
L
Isenovic
Esma R
ER
D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000201:enzymology* / Q000378:metabolism / Q000628:therapy*; D003922:Diabetes Mellitus, Type 1 / Q000201:enzymology* / Q000378:metabolism / Q000628:therapy*; D006801:Humans; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism* / Q000502:physiology; D051381:Rats; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism* / Q000502:physiology
D052247:Nitric Oxide Synthase Type II; D000254:Sodium-Potassium-Exchanging ATPase