The effect of C-peptide on diabetic nephropathy: A review of molecular mechanisms

Abstract

C-peptide is a small peptide connecting two chains of proinsulin molecule and is dissociated before the release of insulin. It is secreted in an equimolar amount to insulin from the pancreatic beta-cells into the circulation. Recent evidence demonstrates that it has other physiologic activities beyond its structural function. C-peptide modulates intracellular signaling pathways in various pathophysiologic states and, could potentially be a new therapeutic target for different disorders including diabetic complications. There is growing evidence that c-peptide has modulatory effects on the molecular mechanisms involved in the development of diabetic nephropathy. Although we have little direct evidence, pharmacological properties of c-peptide suggest that it can provide potent renoprotective effects especially, in a c-peptide deficient milieu as in type 1 diabetes mellitus. In this review, we describe possible molecular mechanisms by which c-peptide may improve renal efficiency in a diabetic milieu.

Proteome Characterization of BALF Extracellular Vesicles in Idiopathic Pulmonary Fibrosis: Unveiling Undercover Molecular Pathways

“…Remarkably, pathways analysis of EVs proteins showed that they are prevalently involved in antigen presentation by MHC class I and II, cytoskeleton remodeling, adenosine signaling, adrenergic signaling, G protein signaling and specific G protein C-peptide signaling, and lipid metabolism. C-peptide (proinsulin), prevalently studied in diabetes, exerts its biological activities via a specific G-protein coupled receptor also expressed on endothelial cells and fibroblasts [42]. Its signaling involves ERK1/2, PI3K-Akt, PKC, eNOS and NF-kB, well-known factors in TGF-β signaling [43,44], the key regulator of fibrosis, thereby suggesting C-peptide involvement in fibrogenic processes [45].…”

Urinary metabolite profiling identifies biomarkers for risk of progression of diabetic nephropathy in 2,670 individuals with type 1 diabetes

“…4 Although the molecular understanding of diabetic nephropathy is expanding, its exact pathophysiology is still elusive. 5 Urinary metabolites are a direct readout of kidney function 6 and might therefore offer novel molecular insights into the pathophysiology of diabetic nephropathy.…”

Effects of Gender-Affirming Hormone Therapy on Insulin Sensitivity and Incretin Responses in Transgender People

“…However, because GLP-1 receptors are also abundantly represented throughout the reproductive system (26), it is has been suggested that incretins and fertility/sex hormones are also interconnected. Indeed, GLP-1 and its receptor agonists are suggested to exert positive influences on different aspects concerning fertility, such as gonadotropin-releasing hormone and leutinizing hormone release (26), polycystic ovary syndrome (26), and male testosterone production; however, results of the latter two might be confounded by the direct or indirect insulin-sensitizing effects of GLP-1 agonists (27), and it therefore remains unclear if, and to what extent, sex hormones and incretins actually affect each other directly, within or without the context of insulin sensitivity.…”