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An update on the potential role of C-peptide in diabetes and osteoporosis

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Abstract

Purpose

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.

Conclusion

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.

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Authors and Affiliations

  1. Clinical Nutrition Unit, Department of Medical and Surgical Science, University Magna Graecia, Catanzaro, 88100, Italy

    Arturo Pujia

  2. Internal and Emergency Medicine and Center for Applied Clinical Research (Ce.R.C.A.) Clinical Institute “Beato Matteo”, Vigevano, 27029, Italy

    Carmine Gazzaruso

  3. Clinical Nutrition Unit, Menopause Clinic, Department of Clinical and Experimental Medicine, University Magna Graecia, Catanzaro, 88100, Italy

    Tiziana Montalcini

Authors
  1. Arturo Pujia
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  2. Carmine Gazzaruso
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  3. Tiziana Montalcini
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Correspondence to Tiziana Montalcini.

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Pujia, A., Gazzaruso, C. & Montalcini, T. An update on the potential role of C-peptide in diabetes and osteoporosis. Endocrine 58, 408–412 (2017). https://doi.org/10.1007/s12020-017-1286-5

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