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Glucose Uptake Measurement and Response to Insulin Stimulation in In Vitro Cultured Human Primary Myotubes
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Glucose-regulated glucose uptake by transplanted muscle cells expressing glucokinase counteracts diabetic

Pedro J Otaegui1, Maria Ontiveros, Tura Ferre

  • 1Department of Biochemistry and Molecular Biology, School of Veterinary Medicine, and Center of Animal Biotechnology and Gene Therapy, Universitat Autònoma de Barcelona, E-08193 Bellaterra, Spain.

Human Gene Therapy
|January 25, 2003
PubMed

Insights

Genetically engineered muscle cells expressing glucokinase (GK) can help manage type 1 diabetes. Transplanted GK-expressing myotubes effectively lowered hyperglycemia in diabetic mice, offering a potential glucose-regulated therapy.

Area of Science:

  • Biotechnology
  • Metabolic Diseases
  • Gene Therapy

Background:

  • Type 1 diabetes management relies on insulin therapy, but chronic hyperglycemia causes severe complications.
  • Effective glycemic control is crucial for preventing microvascular, macrovascular, and neurological damage in diabetic patients.
  • Engineering tissues to enhance glucose disposal offers a novel therapeutic strategy for hyperglycemia.

Purpose of the Study:

  • To investigate the potential of genetically engineered muscle cells expressing glucokinase (GK) as a glucose-regulated therapy for diabetic hyperglycemia.
  • To assess the in vitro glucose uptake and utilization of GK-expressing myoblasts.
  • To evaluate the in vivo efficacy of GK-expressing myotube transplantation in ameliorating hyperglycemia in mouse models of diabetes.

Main Methods:

  • Differentiated myoblast cells were engineered to overexpress the glucokinase (GK) enzyme.
  • In vitro studies assessed glucose uptake and utilization in GK-expressing myoblasts.
  • GK-expressing myotubes and control myotubes were transplanted into healthy and streptozotocin-induced diabetic mice.
  • Blood glucose levels, polydipsia, and polyphagia were monitored post-transplantation.

Main Results:

  • GK-expressing myoblasts demonstrated increased glucose uptake and utilization in a glucose-dependent manner in vitro.
  • Transplantation of GK-expressing myotubes into diabetic mice significantly lowered hyperglycemia, polydipsia, and polyphagia.
  • Control myotube transplants did not improve glycemic control in diabetic mice.
  • Transplantation into healthy mice did not disrupt normoglycemia.

Conclusions:

  • Genetically engineered muscle cells expressing glucokinase hold promise for a glucose-regulated therapeutic approach to manage diabetic hyperglycemia.
  • This strategy offers a potential alternative or adjunct to traditional insulin therapy for type 1 diabetes.
  • Further research into the long-term efficacy and safety of GK-expressing myotube transplantation is warranted.

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