Progressive erosion of ß-cell function precedes the onset of hyperglycemia in the NOD mouse model of type 1 diabetes.
Diabetes
; 60(8): 2086-91, 2011 Aug.
Article
en En
| MEDLINE
| ID: mdl-21659497
ABSTRACT
OBJECTIVE:
A progressive decline in insulin responses to glucose was noted in individuals before the onset of type 1 diabetes. We determined whether such abnormalities occurred in prediabetic NOD mice-the prototypic model for human type 1 diabetes. RESEARCH DESIGN ANDMETHODS:
Morning blood glucose was measured every other day in a cohort of NOD females. Glucose tolerance and insulin secretion were measured longitudinally by intraperitoneal glucose tolerance tests in NOD/ShiLtJ and BALB/cJ mice 6 to 14 weeks of age. Arginine-stimulated insulin secretion and insulin sensitivity were assessed during intraperitoneal arginine or intraperitoneal insulin tolerance tests.RESULTS:
During prediabetes, NOD females displayed a progressive increase in glucose levels followed by an acute onset of hyperglycemia. First-phase insulin responses (FPIRs) during the intraperitoneal glucose tolerance test (IPGTT) declined before loss of glucose tolerance in NOD. The failure of FPIR could be detected, with a decline in peak insulin secretion during IPGTT. Arginine-stimulated insulin secretion remained unchanged during the study period. The decline in insulin secretion in NOD mice could not be explained by changes in insulin sensitivity.CONCLUSIONS:
There was an impressive decline in FPIR before changes in glucose tolerance, suggesting that impairment of FPIR is an early in vivo marker of progressive ß-cell failure in NOD mice and human type 1 diabetes. We portend that these phenotypes in NOD mice follow a similar pattern to those seen in humans with type 1 diabetes and validate, in a novel way, the importance of this animal model for studies of this disease.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Estado Prediabético
/
Diabetes Mellitus Tipo 1
/
Células Secretoras de Insulina
/
Glucosa
/
Hiperglucemia
Límite:
Animals
Idioma:
En
Revista:
Diabetes
Año:
2011
Tipo del documento:
Article
País de afiliación:
Estados Unidos