Glucose-responsive hepatic insulin gene therapy of spontaneously diabetic BB/Wor rats.
Hum Gene Ther
; 14(15): 1401-13, 2003 Oct 10.
Article
en En
| MEDLINE
| ID: mdl-14577921
Hepatic insulin gene therapy (HIGT) ameliorates hyperglycemia in multiple rodent models of diabetes mellitus, with variable degrees of glucose control. We demonstrate here that adenoviral delivery of a glucose-regulated transgene into rat hepatocytes produces near-normal glycemia in spontaneously diabetic BB/Wor rats without administration of exogenous insulin. We compared growth, glycemia, counterregulatory hormones, and lipids in HIGT-treated diabetic rats to nondiabetic rats and diabetic rats treated with either insulin injections or sustained-release insulin pellets. HIGT-treated rats achieved near-normal blood glucose levels within 1 week and maintained glycemic control for up to 3 months. Rats treated with sustained release insulin implants had similar blood sugars, but more hypoglycemia and gained more weight than HIGT-treated rats. HIGT-treated rats normalized blood glucose within 2 hr after a glucose load, and tolerated a 24-hr fast without hypoglycemia. HIGT treatment suppressed ketogenesis similarly to peripheral insulin. However, glucagon levels and free fatty acids were increased in HIGT-treated rats compared to either nondiabetic controls or rats treated with exogenous insulin. In addition to extending successful application of HIGT to a rat model of autoimmune diabetes, these findings emphasize the relative contribution of hepatic insulin effect in the metabolic stabilization of diabetes mellitus.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Terapia Genética
/
Glucosa
/
Insulina
/
Hígado
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Hum Gene Ther
Asunto de la revista:
GENETICA MEDICA
/
TERAPEUTICA
Año:
2003
Tipo del documento:
Article
País de afiliación:
Estados Unidos
Pais de publicación:
Estados Unidos