Renal and vascular benefits of C-peptide: Molecular mechanisms of C-peptide action

Lina Nordquist1, Fredrik Palm1,2, Bradley T Andresen3,41Department of Medical Cell Biology, Division of Integrative Physiology, Uppsala University, Uppsala, Sweden; 2Georgetown University Medical Center, Department of Medicine, Division of Nephrology and Hypertension, Georgetown University, Washington, DC, USA; 3University of Missouri, Department of Internal Medicine, Division of Endocrinology, HSC Diabetes Center, Columbia, MO, USA; 4Harry S Truman VA Medical Center, Columbia, MO, USAAbstract: C-peptide has long been thought to be an inert byproduct of insulin production, but it has become apparent, and accepted, that C-peptide has important biological properties. C-peptide displays beneficial effects in many tissues affected by diabetic complications, such as increased peripheral blood flow and protection from renal damage. However, the mechanisms mediating these effects remain unclear. C-peptide interacts with cellular membranes at unidentified sites distinctive of the insulin family of receptors, and signals to multiple targets known to play a role in diabetes and diabetic complications, such as Na+/K+-ATPase and NOS. In general, the physiological and molecular effects of C-peptide resemble insulin, but C-peptide also possesses traits separate from those of insulin. These basic studies have been confirmed in human studies, suggesting that C-peptide may lend itself to clinical applications. However, the molecular and physiological properties of C-peptide are not completely elucidated, and large clinical studies have not begun. In order to further these goals, we critically summarize the current state of knowledge regarding C-peptide’s renal and vascular effects and the molecular signaling of C-peptide.Keywords: C-peptide, insulin, diabetes mellitus, nephropathy, vascular, signalin