title: An update on the potential role of C-peptide in diabetes and osteoporosis.
abstract: OBJECTIVE
  C-peptide secretion is deficient or absent in type 1 diabetes mellitus. It is well accepted that insulin replacement therapy cannot prevent the development of long-term diabetes-related complications, which can often be disabling or even life-threatening. Several cross-sectional investigations have suggested that residual C-peptide production in patients with type 1 diabetes mellitus would help prevent a number of complications. In animal models of diabetes and in patients with type 1 diabetes mellitus, C-peptide replacement improves renal function, skin and skeletal muscle blood flow, nerve conduction, glucose utilization, and other diabetes-related complications. Recent investigations suggest a new beneficial effect of C-peptide, which to date has never been studied. It is known that osteoporosis is the most prevalent short-term complication in type 1 diabetes mellitus. This review will highlight new insights into the pathophysiology and future therapeutic modalities for osteoporosis in individuals with diabetes.
  
  
  METHODS
  This review provides a concise summary of old and new insights into the role of C-peptide in diabetes-related complications.
  
  
  RESULTS
  The data suggest that C-peptide is a bioactive peptide, acting independently of insulin, which binds to a G-protein-coupled membrane binding site in different cell types. By triggering Ca2+-dependent intracellular signaling pathways, both Na+, K+-ATPase and endothelial nitric oxide synthase are activated. C-peptide may act on osteoblast cells by ERK 1/2 pathway activation, modulate collagen biosynthesis and RANKL expression. Furthermore, C-peptide-deficient postmenopausal women, not affected by diabetes, have a lower bone mineral density than those with normal C-peptide levels.
  
  
  CONCLUSIONS
  Taken together these studies encourage further investigations to elucidate the role of C-peptide in preventing bone loss in type 1 diabetes mellitus and in those individuals with C-peptide deficiency and osteoporosis.
authors.affiliation: Clinical Nutrition Unit, Department of Medical and Surgical Science, University Magna Graecia, Catanzaro, 88100, Italy.
authors.forename: Arturo
authors.initials: A
authors.lastname: Pujia
authors.affiliation: Internal and Emergency Medicine and Center for Applied Clinical Research (Ce.R.C.A.) Clinical Institute "Beato Matteo", Vigevano, 27029, Italy.
authors.forename: Carmine
authors.initials: C
authors.lastname: Gazzaruso
authors.affiliation: Clinical Nutrition Unit, Menopause Clinic, Department of Clinical and Experimental Medicine, University Magna Graecia, Catanzaro, 88100, Italy. tmontalcini@unicz.it.
authors.forename: Tiziana
authors.initials: T
authors.lastname: Montalcini
mesh_terms: D001842:Bone and Bones / Q000473:pathology; D002096:C-Peptide / Q000378:metabolism*; D048909:Diabetes Complications / Q000378:metabolism; D003920:Diabetes Mellitus / Q000378:metabolism*; D050723:Fractures, Bone / Q000453:epidemiology / Q000209:etiology; D006801:Humans; D010024:Osteoporosis / Q000378:metabolism*
chemical_list: D002096:C-Peptide
keywords: C-peptide; Diabetes; Fractures; Intracellular signaling; Osteoporosis