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Effect of GLP-1 Treatment on Bone Turnover in Normal, Type 2 Diabetic, and Insulin-Resistant States

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Abstract

It has been suggested that hormones released after nutrient absorption, such as glucose-dependent insulinotropic peptide (GIP) and glucagon-like peptide 2 (GLP-2), could be responsible for changes in bone resorption. However, information about the role of GLP-1 in this regard is scanty. Diabetes-related bone loss occurs as a consequence of poor control of glucose homeostasis, but the relationship between osteoporosis and type 2 diabetes remains unclear. Since GLP-1 is decreased in the latter condition, we evaluated some bone characteristics in streptozotocin-induced type 2 diabetic (T2D) and fructose-induced insulin-resistant (IR) rat models compared to normal (N) and the effect of GLP-1 or saline (control) treatment (3 days by osmotic pump). Blood was taken before and after treatment for plasma measurements; tibiae and femora were collected for gene expression of bone markers (RT-PCR) and structure (μCT) analysis. Compared to N, plasma glucose and insulin were, respectively, higher and lower in T2D; osteocalcin (OC) and tartrate-resistant alkaline phosphatase 5b were lower; phosphate in IR showed a tendency to be higher; PTH was not different in T2D and IR; all parameters were unchanged after GLP-1 infusion. Bone OC, osteoprotegerin (OPG) and RANKL mRNA were lower in T2D and IR; GLP-1 increased OC and OPG in all groups and RANKL in T2D. Compared to N, trabecular bone parameters showed an increased degree of anisotropy in T2D and IR, which was reduced after GLP-1. These findings show an insulin-independent anabolic effect of GLP-1 and suggest that GLP-1 could be a useful therapeutic agent for improving the deficient bone formation and bone structure associated with glucose intolerance.

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Acknowledgements

This work was supported by CIBERDEM and grants (PI 060076 and PI 050117) from ISCIII, Ministry of Ciencia e Innovación. B. N., P. M., and J. C. are research fellows from Fundación Conchita Rábago de Jiménez Díaz and J. J. H. is a research fellow from Fundación IMABIS. We thank Estrella Martín-Crespo for excellent technical assistance; Amelia Porres for measuring plasma calcium, phosphate, and creatinine; and Mark Davis for proofreading the manuscript.

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Authors and Affiliations

  1. Department of Metabolism, Nutrition, and Hormones, Fundación Jiménez Díaz, Avda. Reyes Católicos 2, 28040, Madrid, Spain

    Bernardo Nuche-Berenguer, Paola Moreno, Jesús Cancelas, Juan J. Haro-Mora & María L. Villanueva-Peñacarrillo

  2. Bone and Mineral Metabolism Laboratory, Fundación Jiménez Díaz, 28040, Madrid, Spain

    Pedro Esbrit

  3. Trabeculae, Parque Tecnológico de Galicia, Edificio CEI, Nido 39-32900, San Cibrao das Viñas, Orense, Spain

    Sonia Dapía & José R. Caeiro

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  1. Bernardo Nuche-Berenguer
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  2. Paola Moreno
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  3. Pedro Esbrit
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  4. Sonia Dapía
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  7. Juan J. Haro-Mora
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  8. María L. Villanueva-Peñacarrillo
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Correspondence to María L. Villanueva-Peñacarrillo.

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Nuche-Berenguer, B., Moreno, P., Esbrit, P. et al. Effect of GLP-1 Treatment on Bone Turnover in Normal, Type 2 Diabetic, and Insulin-Resistant States. Calcif Tissue Int 84, 453–461 (2009). https://doi.org/10.1007/s00223-009-9220-3

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  • DOI: https://doi.org/10.1007/s00223-009-9220-3

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