Skeletal myoblast transplantation for attenuation of hyperglycaemia, hyperinsulinaemia and glucose intolerance in a mouse model of type 2 diabetes mellitus.

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  • Additional Information
    • Source:
      Publisher: Springer Verlag Country of Publication: Germany NLM ID: 0006777 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1432-0428 (Electronic) Linking ISSN: 0012186X NLM ISO Abbreviation: Diabetologia Subsets: MEDLINE
    • Publication Information:
      Original Publication: Berlin Springer Verlag
    • Subject Terms:
      Diabetes Mellitus, Type 2/*surgery ; Glucose Intolerance/*surgery ; Muscle Fibers, Skeletal/*transplantation; Animals ; Blood Glucose/metabolism ; Cell Survival ; Diabetes Mellitus, Type 2/blood ; Glucose Intolerance/blood ; Glucose Tolerance Test ; Humans ; Hyperglycemia/surgery ; Hyperinsulinism/surgery ; Immunohistochemistry ; Mice ; Models, Animal ; Muscle Fibers, Skeletal/pathology ; Time Factors ; Transplantation, Heterologous
    • Abstract:
      Aims/hypothesis: We aimed to demonstrate the feasibility and efficacy of intra-muscular transplantation of human skeletal myoblasts (hSkMs) for attenuation of hyperglycaemia and improvement of insulin sensitivity using a mouse model of type 2 diabetes mellitus.
      Methods: KK Cg-Ay/J mice, aged 12 to 14 weeks, underwent an initial intraperitoneal glucose tolerance test (GTT) and were divided into the following groups: KK control group, basal medium (M199) only; KK myoblast group, with hSkM transplantation; KK fibroblast group, with human fibroblast transplantation. Non-diabetic C57BL mice were used as an additional normal control and also had hSkM transplantation. Cells were transplanted intra-muscularly into the skeletal muscles of the mice. All animals were treated with ciclosporin for 6 weeks only. HbA(1c) and fasting GTT, as well as serum adiponectin, cholesterol, insulin and triacylglycerol were studied.
      Results: Immunohistochemistry studies showed extensive survival of the transplanted hSkMs in the skeletal muscles at 12 weeks, with nuclei of the hSkMs integrated into the host muscle fibres. Repeat GTT showed a significant decrease in glucose concentrations in the KK myoblast group compared with the KK control and KK fibroblast groups. The KK myoblast group also had reduced mean HbA(1c), cholesterol, insulin and triacylglycerol, and increased adiponectin compared with the KK control and KK fibroblast groups. C57BL mice showed no change in glucose homeostasis after hSkM transplant.
      Conclusions/interpretation: Human skeletal myoblast transplantation attenuated hyperglycaemia and hyperinsulinaemia and improved glucose tolerance in the KK mouse. This novel approach of improving muscle insulin resistance may be a potential alternative treatment for type 2 diabetes mellitus.
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    • Accession Number:
      0 (Blood Glucose)
    • Publication Date:
      Date Created: 20090714 Date Completed: 20100108 Latest Revision: 20211020
    • Publication Date:
      20231215
    • Accession Number:
      10.1007/s00125-009-1421-9
    • Accession Number:
      19593542