Prolonged survival and improved glycemia in BioBreeding diabetic rats after early sustained exposure to glucagon-like peptide
Yanay, Ofer ; Moralejo, Daniel H. ; Kernan, Kelly ; Brzezinski, Margaret ; Fuller, Jessica M. LU ; Barton, Randall W. ; Lernmark, Ake LU
and Osborne, William R.
(2010)
In Journal of Gene Medicine
12(6).
p.538-544
- Abstract
Background: Type 1 diabetes (T1D) in both humans and BioBreeding (BB) rats is an autoimmune disease that results in complete destruction of islets and insulin dependency for life. Glucagon-like peptide 1 (GLP-1) promotes β cell proliferation and neogenesis and has a potent insulinotropic effect. We hypothesized that the expression of GLP-1 before disease onset would increase islet mass, delay diabetes and prolong survival of BB rats. Methods: Vascular smooth muscle cells retrovirally transduced to secrete GLP-1 were seeded into TheraCyte™ encapsulation devices, implanted subcutaneously, and rats were monitored for diabetes. Results: In untreated control rats, plasma GLP-1 levels were 34.5-39.5 pmol/l, whereas, in treated rats, plasma... (More)
Background: Type 1 diabetes (T1D) in both humans and BioBreeding (BB) rats is an autoimmune disease that results in complete destruction of islets and insulin dependency for life. Glucagon-like peptide 1 (GLP-1) promotes β cell proliferation and neogenesis and has a potent insulinotropic effect. We hypothesized that the expression of GLP-1 before disease onset would increase islet mass, delay diabetes and prolong survival of BB rats. Methods: Vascular smooth muscle cells retrovirally transduced to secrete GLP-1 were seeded into TheraCyte™ encapsulation devices, implanted subcutaneously, and rats were monitored for diabetes. Results: In untreated control rats, plasma GLP-1 levels were 34.5-39.5 pmol/l, whereas, in treated rats, plasma levels were elevated, in the range 90-250.4 pmol/l. Hypoglycemia was not detected and this was anticipated from the glucose-regulated action of GLP-1. Diabetes onset (mean ± SEM) in untreated rats occurred at 56.5 ± 0.6 days (n = 6) and, in GLP-1-treated rats, was delayed until 76.4 ± 3.3 days (n = 5) (p < 0.001). After disease onset, untreated control rats showed a rapid weight loss and elevated blood glucose (>650 mg/dl) and did not survive beyond 11 days. At 5 days after diabetes onset, insulin-secreting islets were absent in untreated rats. By contrast, treated rats maintained weight for up to 143 days of age and showed insulin-secreting β cells. Conclusions: Sustained GLP-1 expression delivered by encapsulated cells before diabetes onset in BB rats showed an improved clinical outcome, suggesting the potential for treating patients using long lasting GLP-1 analogs.
(Less)
- author
- Yanay, Ofer
; Moralejo, Daniel H.
; Kernan, Kelly
; Brzezinski, Margaret
; Fuller, Jessica M.
LU
; Barton, Randall W.
; Lernmark, Ake
LU
and Osborne, William R.
- publishing date
- 2010
- type
- Contribution to journal
- publication status
- published
- keywords
- BB rats, Bioisolator, Diabetes, GLP-1, β cells
- in
- Journal of Gene Medicine
- volume
- 12
- issue
- 6
- pages
- 7 pages
- publisher
- John Wiley & Sons Inc.
- external identifiers
-
- scopus:77954574031
- pmid:20527046
- ISSN
- 1099-498X
- DOI
- 10.1002/jgm.1466
- language
- English
- LU publication?
- no
- id
- 1cc0597c-de4c-4d8b-9aac-071fe5c87237
- date added to LUP
- 2017-09-07 12:10:10
- date last changed
- 2024-03-13 08:08:13
@article{1cc0597c-de4c-4d8b-9aac-071fe5c87237,
abstract = {{<p>Background: Type 1 diabetes (T1D) in both humans and BioBreeding (BB) rats is an autoimmune disease that results in complete destruction of islets and insulin dependency for life. Glucagon-like peptide 1 (GLP-1) promotes β cell proliferation and neogenesis and has a potent insulinotropic effect. We hypothesized that the expression of GLP-1 before disease onset would increase islet mass, delay diabetes and prolong survival of BB rats. Methods: Vascular smooth muscle cells retrovirally transduced to secrete GLP-1 were seeded into TheraCyte™ encapsulation devices, implanted subcutaneously, and rats were monitored for diabetes. Results: In untreated control rats, plasma GLP-1 levels were 34.5-39.5 pmol/l, whereas, in treated rats, plasma levels were elevated, in the range 90-250.4 pmol/l. Hypoglycemia was not detected and this was anticipated from the glucose-regulated action of GLP-1. Diabetes onset (mean ± SEM) in untreated rats occurred at 56.5 ± 0.6 days (n = 6) and, in GLP-1-treated rats, was delayed until 76.4 ± 3.3 days (n = 5) (p < 0.001). After disease onset, untreated control rats showed a rapid weight loss and elevated blood glucose (>650 mg/dl) and did not survive beyond 11 days. At 5 days after diabetes onset, insulin-secreting islets were absent in untreated rats. By contrast, treated rats maintained weight for up to 143 days of age and showed insulin-secreting β cells. Conclusions: Sustained GLP-1 expression delivered by encapsulated cells before diabetes onset in BB rats showed an improved clinical outcome, suggesting the potential for treating patients using long lasting GLP-1 analogs.</p>}},
author = {{Yanay, Ofer and Moralejo, Daniel H. and Kernan, Kelly and Brzezinski, Margaret and Fuller, Jessica M. and Barton, Randall W. and Lernmark, Ake and Osborne, William R.}},
issn = {{1099-498X}},
keywords = {{BB rats; Bioisolator; Diabetes; GLP-1; β cells}},
language = {{eng}},
number = {{6}},
pages = {{538--544}},
publisher = {{John Wiley & Sons Inc.}},
series = {{Journal of Gene Medicine}},
title = {{Prolonged survival and improved glycemia in BioBreeding diabetic rats after early sustained exposure to glucagon-like peptide}},
url = {{http://dx.doi.org/10.1002/jgm.1466}},
doi = {{10.1002/jgm.1466}},
volume = {{12}},
year = {{2010}},
}