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A new stable GIP-Oxyntomodulin hybrid peptide improved bone strength both at the organ and tissue levels in genetically-inherited type 2 diabetes mellitus.

Mansur, SA, Mieczkowska, A, Flatt, Peter, Bouvard, B, Chappard, D, Irwin, Nigel and Mabilleau, G (2016) A new stable GIP-Oxyntomodulin hybrid peptide improved bone strength both at the organ and tissue levels in genetically-inherited type 2 diabetes mellitus. Bone, 87 . pp. 102-113. [Journal article]

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DOI: 10.1016/j.bone.2016.04.001

Abstract

Obesity and type 2 diabetes mellitus (T2DM) progress worldwide with detrimental effects on several physiological systems including bone tissue mainly by affecting bone quality. Several gut hormones analogues have been proven potent in ameliorating bone quality. In the present study, we used the leptin receptor-deficient db/db mice as a model of obesity and severe T2DM to assess the extent of bone quality alterations at the organ and tissue levels. We also examined the beneficial effects of gut hormone therapy in this model by using a new triple agonist ([d-Ala2]GIP-Oxm) active at the GIP, GLP-1 and glucagon receptors. As expected, db/db mice presented with dramatic alterations of bone strength at the organ level associated with deterioration of trabecular and cortical microarchitectures and an augmentation in osteoclast numbers. At the tissue level, these animals presented also with alterations of bone strength (reduced hardness, indentation modulus and dissipated energy) with modifications of tissue mineral distribution, collagen glycation and collagen maturity. The use of [d-Ala2]GIP-Oxm considerably improved bone strength at the organ level with modest effects on trabecular microarchitecture. At the tissue level, [d-Ala2]GIP-Oxm ameliorated bone strength reductions with positive effects on collagen glycation and collagen maturity. This study provides support for including gut hormone analogues as possible new therapeutic strategies for improving bone quality in bone complications associated to T2DM.

Item Type:Journal article
Keywords:Type 2 diabetes mellitus; [d-Ala2]GIP–Oxm; Bone quality; Bone strength; db/db mice
Faculties and Schools:Faculty of Life and Health Sciences > School of Pharmacy and Pharmaceutical Science
Faculty of Life and Health Sciences > School of Biomedical Sciences
Faculty of Life and Health Sciences
Research Institutes and Groups:Biomedical Sciences Research Institute
Biomedical Sciences Research Institute > Pharmacy & Pharmaceutical Sciences
Biomedical Sciences Research Institute > Diabetes
ID Code:34514
Deposited By: Dr Nigel Irwin
Deposited On:26 Apr 2016 09:25
Last Modified:23 Jul 2018 18:47

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