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

Moralejo, Daniel H.; Yanay, Ofer; Kernan, Kelly; Bailey, Adam; Lernmark, Ake LU and Osborne, William (2011) In Journal of Bioscience and Bioengineering 111(4). p.383-387
Abstract

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... (More)

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.

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author
publishing date
type
Contribution to journal
publication status
published
keywords
β cells, Bioisolator, Diabetes, Encapsulated cells, GLP-1
in
Journal of Bioscience and Bioengineering
volume
111
issue
4
pages
5 pages
publisher
Elsevier
external identifiers
  • scopus:79953321386
ISSN
1389-1723
DOI
10.1016/j.jbiosc.2010.12.008
language
English
LU publication?
no
id
4ddec768-5a00-4397-b02f-246e1c68e1ec
date added to LUP
2017-09-07 12:39:22
date last changed
2017-09-07 12:39:22
@article{4ddec768-5a00-4397-b02f-246e1c68e1ec,
  abstract     = {<p>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 TheraCyte<sup>TM</sup> 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&lt;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&lt;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.</p>},
  author       = {Moralejo, Daniel H. and Yanay, Ofer and Kernan, Kelly and Bailey, Adam and Lernmark, Ake and Osborne, William},
  issn         = {1389-1723},
  keyword      = {β cells,Bioisolator,Diabetes,Encapsulated cells,GLP-1},
  language     = {eng},
  number       = {4},
  pages        = {383--387},
  publisher    = {Elsevier},
  series       = {Journal of Bioscience and Bioengineering},
  title        = {Sustained glucagon-like peptide 1 expression from encapsulated transduced cells to treat obese diabetic rats},
  url          = {http://dx.doi.org/10.1016/j.jbiosc.2010.12.008},
  volume       = {111},
  year         = {2011},
}