Combination therapy with glucagon-like peptide-1 and gastrin restores normoglycemia in diabetic NOD mice.
Diabetes
; 57(12): 3281-8, 2008 Dec.
Article
em En
| MEDLINE
| ID: mdl-18835930
ABSTRACT
OBJECTIVE:
Glucagon-like peptide-1 (GLP-1) and gastrin promote pancreatic beta-cell function, survival, and growth. Here, we investigated whether GLP-1 and gastrin can restore the beta-cell mass and reverse hyperglycemia in NOD mice with autoimmune diabetes. RESEARCH DESIGN ANDMETHODS:
Acutely diabetic NOD mice were treated with GLP-1 and gastrin, separately or together, twice daily for 3 weeks. Blood glucose was measured weekly and for a further 5 weeks after treatments, after which pancreatic insulin content and beta-cell mass, proliferation, neogenesis, and apoptosis were measured. Insulin autoantibodies were measured, and adoptive transfer of diabetes and syngeneic islet transplant studies were done to evaluate the effects of GLP-1 and gastrin treatment on autoimmunity.RESULTS:
Combination therapy with GLP-1 and gastrin, but not with GLP-1 or gastrin alone, restored normoglycemia in diabetic NOD mice. The GLP-1 and gastrin combination increased pancreatic insulin content, beta-cell mass, and insulin-positive cells in pancreatic ducts, and beta-cell apoptosis was decreased. Insulin autoantibodies were reduced in GLP-1- and gastrin-treated NOD mice, and splenocytes from these mice delayed adoptive transfer of diabetes in NOD-scid mice. Syngeneic islet grafts in GLP-1 -and gastrin-treated NOD mice were infiltrated by leukocytes with a shift in cytokine expression from interferon-gamma to transforming growth factor-beta1, and beta-cells were protected from apoptosis.CONCLUSIONS:
Combination therapy with GLP-1 and gastrin restores normoglycemia in diabetic NOD mice by increasing the pancreatic beta-cell mass and downregulating the autoimmune response.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Glicemia
/
Gastrinas
/
Diabetes Mellitus Tipo 1
/
Peptídeo 1 Semelhante ao Glucagon
Limite:
Animals
Idioma:
En
Revista:
Diabetes
Ano de publicação:
2008
Tipo de documento:
Article
País de afiliação:
Canadá