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

Abstract

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.

• Authors: Zorica Zakula, Goran Koricanac, Biljana Putnikovic, Ljiljana Markovic, Esma R Isenovic
• Journal: Medical hypotheses (Med Hypotheses) Vol. 69 Issue 2 Pg. 302-6 ( 2007) ISSN: 0306-9877 [Print] United States
• PMID: 17289286 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Nitric Oxide Synthase Type II
• Sodium-Potassium-Exchanging ATPase

Topics

• Animals
• Diabetes Mellitus, Experimental (enzymology, metabolism, therapy)
• Diabetes Mellitus, Type 1 (enzymology, metabolism, therapy)
• Humans
• Nitric Oxide Synthase Type II (metabolism, physiology)
• Rats
• Sodium-Potassium-Exchanging ATPase (metabolism, physiology)