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Sustained glucagon-like peptide 1 expression from encapsulated transduced cells to treat obese diabetic rats

Author:
  • Daniel H. Moralejo
  • Ofer Yanay
  • Kelly Kernan
  • Adam Bailey
  • Ake Lernmark
  • William Osborne
Publishing year: 2011-04
Language: English
Pages: 383-387
Publication/Series: Journal of Bioscience and Bioengineering
Volume: 111
Issue: 4
Document type: Journal article
Publisher: Elsevier

Abstract english

Obesity and type 2 diabetes (T2D) are two prevalent chronic diseases that have become a major public health concern in industrialized countries. T2D is characterized by hyperglycemia and islet beta cell dysfunction. Glucagon-like peptide 1 (GLP-1) promotes β cell proliferation and neogenesis and has a potent insulinotropic effect. Leptin receptor deficient male rats are obese and diabetic and provide a model of T2D. We hypothesized that their treatment by sustained expression of GLP-1 using encapsulated cells may prevent or delay diabetes onset. Vascular smooth muscle cells (VSMC) retrovirally transduced to secrete GLP-1 were seeded into TheraCyteTM encapsulation devices, implanted subcutaneously and rats were monitored for diabetes. Rats that received cell implants showed mean plasma GLP-1 level of 119.3±10.2pM that was significantly elevated over control values of 32.4±2.9pM (P<0.001). GLP-1 treated rats had mean insulin levels of 45.9±2.3ng/ml that were significantly increased over control levels of 7.3±1.5ng/ml (P<0.001). In rats treated before diabetes onset elevations in blood glucose were delayed and rats treated after onset became normoglycemic and showed improved glucose tolerance tests. Untreated diabetic rats possess abnormal islet structures characterized by enlarged islets with α-cell infiltration and multifocal vacuolization. GLP-1 treatment induced normalization of islet structures including a mantle of α-cells and increased islet mass. These data suggest that encapsulated transduced cells may offer a potential long term treatment of patients.

Keywords

  • β cells
  • Bioisolator
  • Diabetes
  • Encapsulated cells
  • GLP-1

Other

Published
  • ISSN: 1389-1723
E-mail: ake [dot] lernmark [at] med [dot] lu [dot] se

Principal investigator

Diabetes and Celiac Unit

+46 40 39 19 01

+46 70 616 47 79

60:11:015

Jan Waldenströms gata 35, Malmö

33

Lund University Diabetes Centre, CRC, SUS Malmö, Jan Waldenströms gata 35, House 91:12. SE-214 28 Malmö. Telephone: +46 40 39 10 00