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- Title
Progressive erosion of β-cell function precedes the onset of hyperglycemia in the NOD mouse model of type 1 diabetes.
- Authors
Ize-Ludlow D; Lightfoot YL; Parker M; Xue S; Wasserfall C; Haller MJ; Schatz D; Becker DJ; Atkinson MA; Mathews CE; Ize-Ludlow, Diego; Lightfoot, Yaima L; Parker, Matthew; Xue, Song; Wasserfall, Clive; Haller, Michael J; Schatz, Desmond; Becker, Dorothy J; Atkinson, Mark A; Mathews, Clayton E
- Abstract
<bold>Objective: </bold>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.<bold>Research Design and Methods: </bold>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.<bold>Results: </bold>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.<bold>Conclusions: </bold>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 β-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.
- Publication
Diabetes, 2011, Vol 60, Issue 8, p2086
- ISSN
0012-1797
- Publication type
journal article
- DOI
10.2337/db11-0373