Regulation of the inducible nitric oxide synthase and sodium pump in type 1 diabetes

• Published in: Medical hypotheses 2007, Vol.69 (2), p.302-306
• Main Authors: Zakula, Zorica, Koricanac, Goran, Putnikovic, Biljana, Markovic, Ljiljana, Isenovic, Esma R
• Format: Article
• Language: English
• Subjects: Animals; Diabetes Mellitus, Experimental - enzymology; Diabetes Mellitus, Experimental - metabolism; Diabetes Mellitus, Experimental - therapy; Diabetes Mellitus, Type 1 - enzymology; Diabetes Mellitus, Type 1 - metabolism; Diabetes Mellitus, Type 1 - therapy; Humans; Internal Medicine; Nitric Oxide Synthase Type II - metabolism; Nitric Oxide Synthase Type II - physiology; Rats; Sodium-Potassium-Exchanging ATPase - metabolism; Sodium-Potassium-Exchanging ATPase - physiology
• ISSN: 0306-9877; 1532-2777
• DOI: 10.1016/j.mehy.2006.11.045

Summary 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 (cPLA2 )/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/cPLA2 /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.