C-peptide: New findings and therapeutic possibilities

Peripheral Neuropathy in Mouse Models of Diabetes

“…The dominant focus on hyperglycemia as a primary cause of clinical and experimental diabetic neuropathy (Tomlinson and Gardiner, 2008) has more recently been complemented by recognition that deficiency of insulin and C-peptide, in their capacity as neurotrophic-like factors, may also have a distinct pathogenic role (Wahren and Larsson, 2015; Xu et al, 2004). How insulinopenia and hyperglycemia are generated in specific models of type 1 diabetes has, historically, not been a particularly pertinent consideration when investigating mechanisms underlying neuropathy.…”

The Physiology of Proinsulin C-Peptide: Unanswered Questions and a Proposed Model

“…Despite this fact, C-peptide does not appear to directly alter glucose metabolism (12,25,47,52). However, it does appear that C-peptide-and insulin-initiated signaling cascades interact (FIGURE 2) and that this interaction is important for the normal functioning of both peptides, particularly in erythrocytes (39 -41).…”

“…It is now known that C-peptide is a biologically active peptide, although its physiological significance in normal physiology has not been fully elucidated. Although the role of C-peptide in mitigating diabetes-related complications (20,33,36), its potential clinical relevance in diabetes (20,33,47,52), and proposed signaling mechanisms underlying these effects (18,19) have been reviewed elsewhere, multiple questions remain. First, are the effects of C-peptide receptor mediated, and, if so, what is the C-peptide receptor(s)?…”

A Study of Association of C-Peptide with Diabetic Peripheral Neuropathy

“…Experimental studies in type 1 diabetes showed that C-peptide specifically bound to cell surfaces, acting via a Gprotein-related receptor; it also led to autophosphorylation of the insulin receptor in the presence of insulin [20] . Moreover, C-peptide stimulated p38 MAP-kinase and PI-3 kinase activities, and diminished the activation of JNK phosphorylation with subsequent effects on Na + /K + -ATPase activity and nitric oxide (NO) [21,22] . C-peptide also ameliorated the altered expression of insulin-like growth factor-1, nerve growth factor and neurotrophin-3 and their respective receptors, which corrected neurofilament (NF) and tubulin mRNA, and protein expression, as well as normalized the aberrant phosphorylation of NFs [23] .…”