title: Skeletal myoblast transplantation for attenuation of hyperglycaemia, hyperinsulinaemia and glucose intolerance in a mouse model of type 2 diabetes mellitus.
abstract: OBJECTIVE
  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
  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.
authors: National University Medical Institutes, National University of Singapore, Singapore, Republic of Singapore.
authors: L
authors: L
authors: Ye
authors: K O
authors: KO
authors: Lee
authors: L P
authors: LP
authors: Su
authors: W C
authors: WC
authors: Toh
authors: H K
authors: HK
authors: Haider
authors: P K
authors: PK
authors: Law
authors: W
authors: W
authors: Zhang
authors: S P
authors: SP
authors: Chan
authors: E K W
authors: EK
authors: Sim
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002470:Cell Survival; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000601:surgery*; D018149:Glucose Intolerance / Q000097:blood / Q000601:surgery*; D005951:Glucose Tolerance Test; D006801:Humans; D006943:Hyperglycemia / Q000601:surgery; D006946:Hyperinsulinism / Q000601:surgery; D007150:Immunohistochemistry; D051379:Mice; D023421:Models, Animal; D018485:Muscle Fibers, Skeletal / Q000473:pathology / Q000637:transplantation*; D013997:Time Factors; D014183:Transplantation, Heterologous
chemical_list: D001786:Blood Glucose