title: Stable Incretin Mimetics Counter Rapid Deterioration of Bone Quality in Type 1 Diabetes Mellitus.
abstract: Type 1 diabetes mellitus is associated with a high risk for bone fractures. Although bone mass is reduced, bone quality is also dramatically altered in this disorder. However, recent evidences suggest a beneficial effect of the glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1) pathways on bone quality. The aims of the present study were to conduct a comprehensive investigation of bone strength at the organ and tissue level; and to ascertain whether enzyme resistant GIP or GLP-1 mimetic could be beneficial in preventing bone fragility in type 1 diabetes mellitus. Streptozotocin-treated mice were used as a model of type 1 diabetes mellitus. Control and streptozotocin-diabetic animals were treated for 21 days with an enzymatic-resistant GIP peptide ([D-Ala(2) ]GIP) or with liraglutide (each at 25 nmol/kg bw, ip). Bone quality was assessed at the organ and tissue level by microCT, qXRI, 3-point bending, qBEI, nanoindentation, and Fourier-transform infrared microspectroscopy. [D-Ala2]GIP and liraglutide treatment did prevent loss of whole bone strength and cortical microstructure in the STZ-injected mice. However, tissue material properties were significantly improved in STZ-injected animals following treatment with [D-Ala2]GIP or liraglutide. Treatment of STZ-diabetic mice with [D-Ala(2) ]GIP or liraglutide was capable of significantly preventing deterioration of the quality of the bone matrix. Further studies are required to further elucidate the molecular mechanisms involved and to validate whether these findings can be translated to human patients.
authors.affiliation: School of Biomedical Sciences, Ulster University, Coleraine, United Kingdom.|University Tun Hussein Onn Malaysia, Johor, Malaysia.
authors.forename: Sity Aishah
authors.initials: SA
authors.lastname: Mansur
authors.affiliation: GEROM-LHEA, Institut de Biologie en Santé, LUNAM Université, Angers, France.
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Mieczkowska
authors.affiliation: GEROM-LHEA, Institut de Biologie en Santé, LUNAM Université, Angers, France.
authors.forename: Béatrice
authors.initials: B
authors.lastname: Bouvard
authors.affiliation: School of Biomedical Sciences, Ulster University, Coleraine, United Kingdom.
authors.forename: Peter R
authors.initials: PR
authors.lastname: Flatt
authors.affiliation: GEROM-LHEA, Institut de Biologie en Santé, LUNAM Université, Angers, France.|SCIAM, Institut de Biologie en Santé, LUNAM Université, Angers, France.
authors.forename: Daniel
authors.initials: D
authors.lastname: Chappard
authors.affiliation: School of Biomedical Sciences, Ulster University, Coleraine, United Kingdom.
authors.forename: Nigel
authors.initials: N
authors.lastname: Irwin
authors.affiliation: GEROM-LHEA, Institut de Biologie en Santé, LUNAM Université, Angers, France.|SCIAM, Institut de Biologie en Santé, LUNAM Université, Angers, France.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Mabilleau
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena; D015519:Bone Density / Q000187:drug effects; D050071:Bone Density Conservation Agents / Q000494:pharmacology*; D016723:Bone Remodeling / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D005749:Gastric Inhibitory Polypeptide / Q000494:pharmacology*; D052216:Glucagon-Like Peptide 1 / Q000031:analogs & derivatives* / Q000494:pharmacology; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D054795:Incretins / Q000494:pharmacology*; D000069450:Liraglutide; D008297:Male; D051379:Mice; D015591:Microspectrophotometry; D010006:Osteoblasts / Q000187:drug effects / Q000378:metabolism; D010010:Osteoclasts / Q000187:drug effects / Q000378:metabolism; D017550:Spectroscopy, Fourier Transform Infrared; D013977:Tibia / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D013997:Time Factors; D055114:X-Ray Microtomography
chemical_list: D050071:Bone Density Conservation Agents; D007004:Hypoglycemic Agents; D054795:Incretins; C557888:glucose-dependent insulinotropic polypeptide, Ala(2)-; D005749:Gastric Inhibitory Polypeptide; D000069450:Liraglutide; D052216:Glucagon-Like Peptide 1