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Effects of C-Peptide Replacement Therapy on Bone Microarchitecture Parameters in Streptozotocin-Diabetic Rats

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Abstract

C-peptide therapy protects against diabetic micro- and macrovascular damages and neuropatic complications. However, to date, the role of C-peptide in preventing diabetes-related bone loss has not been investigated. Our aim was to evaluate if C-peptide infusion improves bone quality in diabetic rats. Twenty-three male Wistar rats were randomly divided into three groups: normal control group; sham diabetic control group; diabetic plus C-peptide group. Diabetes was induced by streptozotocin injection and C-peptide was delivered subcutaneously for 6 weeks. We performed micro-CT and histological testing to assess several trabecular microarchitectural parameters. At the end, diabetic plus C-peptide rats had a higher serum C-peptide (p = 0.02) and calcium (p = 0.04) levels and tibia weight (p = 0.02) than the diabetic control group. The diabetic plus C-peptide group showed a higher trabecular thickness and cross-sectional thickness than the diabetic control group (p = 0.01 and p = 0.03). Both the normal control and diabetic plus C-peptide groups had more Runx-2 and PLIN1 positive cells in comparison with the diabetic control group (p = 0.045 and p = 0.034). Diabetic rats receiving C-peptide had higher quality of trabecular bone than diabetic rats not receiving this treatment. If confirmed, C-peptide could have a role in improving bone quality in diabetes.

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Acknowledgement

We are grateful to Dr John Wahren, from Karolinska Institutet, Stockholm, Sweden, for providing Rat C-Peptide.

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Author information

Author notes

  1. Samantha Maurotti and Cristina Russo have contributed equally to this work.

Authors and Affiliations

  1. Department of Medical and Surgical Science, Magna Græcia University of Catanzaro, 88100, Catanzaro, Italy

    Samantha Maurotti, Elisa Mazza, Roberta Pujia, Stefano Romeo & Arturo Pujia

  2. Department of Clinical and Experimental Medicine, Magna Græcia University of Catanzaro, Viale S. Venuta, 88100, Catanzaro, Italy

    Cristina Russo & Tiziana Montalcini

  3. IRC-FSH Interregional Center for Food Safety and Health, Department of Health Sciences, Magna Græcia University of Catanzaro, Catanzaro, Italy

    Vincenzo Musolino, Saverio Nucera, Micaela Gliozzi, Miriam Scicchitano, Francesca Bosco & Vincenzo Mollace

  4. Department of Health Sciences, Magna Græcia University of Catanzaro, Catanzaro, Italy

    Valeria Maria Morittu, Monica Ragusa & Domenico Britti

  5. Diabetes and Endocrine and Metabolic Diseases Unit and the Centre for Applied Clinical Research (Ce.R.C.A.) Clinical Institute “Beato Matteo” (Hospital Group San Donato), 27029, Vigevano, Italy

    Carmine Gazzaruso

  6. Department of Medicine, Specialized Regional Center for Biomolecular and Histomorphometric Research On Degenerative and Skelatal Diseases, Verona, Italy

    Maria Teresa Valenti, Michela Deiana & Luca Dalle Carbonare

  7. Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, 37134, Verona, Italy

    Michela Deiana

  8. Department of Molecular and Clinical Medicine, Sahlgrenska Center for Cardiovascolar and Metabolic Research, University of Gothenburg, 42246, Göteborg, Sweden

    Stefano Romeo

  9. Department of Medicine, University of Padova and Regional Center for Osteoporosis, Clinica Medica 1, Padova, Italy

    Sandro Giannini

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  1. Samantha Maurotti
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  2. Cristina Russo
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Contributions

SM, CR, MG, MS, FB, EM contributed to the experimental work. SM, CR and VM are guarantor of the integrity of the data; VM and SN performed microCT assessment; RP was responsible for the glucose monitoring and insulin injection planning; MTV, MD, SG and LDC performed the histological assessment; VMM, MR and DB performed all the laboratory measurements; SR, VM, AP and TM designed the study and prepared the first draft of the paper. TM and CG were responsible for statistical analysis of the data. All authors revised the paper critically for intellectual content and approved the final version.

Corresponding author

Correspondence to Tiziana Montalcini.

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Conflict of interest

All authors declared there were no conflict of interests involved.

Ethical Approval

The experiments were carried out following the European guidelines (2010/63/EU) regarding procedures with animals used, in accordance with the approval of the Ethics Committee for Experimental Animals Welfare of the University Magna Grecia, Catanzaro (Auth. 10/01/2018) and Italian Ministry of Health (Auth. No 353/2018-protocol ADEAB.16, Auth. 9/05/2018).

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Maurotti, S., Russo, C., Musolino, V. et al. Effects of C-Peptide Replacement Therapy on Bone Microarchitecture Parameters in Streptozotocin-Diabetic Rats. Calcif Tissue Int 107, 266–280 (2020). https://doi.org/10.1007/s00223-020-00716-0

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