Prolonged survival and improved glycemia in BioBreeding diabetic rats after early sustained exposure to glucagon-like peptide 1.
J Gene Med
; 12(6): 538-44, 2010 Jun.
Article
em En
| MEDLINE
| ID: mdl-20527046
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 beta 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 + or - SEM) in untreated rats occurred at 56.5 + or - 0.6 days (n = 6) and, in GLP-1-treated rats, was delayed until 76.4 + or - 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 beta 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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Glicemia
/
Ratos Endogâmicos BB
/
Diabetes Mellitus Experimental
/
Peptídeo 1 Semelhante ao Glucagon
Tipo de estudo:
Diagnostic_studies
Limite:
Animals
/
Female
/
Humans
/
Male
Idioma:
En
Revista:
J Gene Med
Assunto da revista:
BIOLOGIA MOLECULAR
/
GENETICA MEDICA
Ano de publicação:
2010
Tipo de documento:
Article
País de afiliação:
Estados Unidos