Volume 1 Supplement 1
Increased insulin resistance compounded by reduced insulin sensitivity drives the "Fat Aussie" (Alms1foz/foz) model of Alström syndrome towards obesity and type 2 diabetes mellitus
© Girard and Petrovsky; licensee BioMed Central Ltd. 2012
Published: 16 November 2012
The Fat Aussie mouse carries a spontaneous mutation (foz) resulting in a premature stop codon in exon 8 of the Alms1 gene and is a model for Alström syndrome. From 60 days of age onwards Alms1foz/foz mice exhibit a strong metabolic phenotype leading to severe obesity and type 2 diabetes mellitus (T2DM).
Investigate whether peripheral insulin resistance or a beta-cell insulin secretory defect comes first in young, non-obese pre-diabetic Alms1foz/foz mice.
Insulin tolerance tests (ITT), glucose tolerance tests (GTT), fasting and post-challenge serum insulin levels and HOMA-IR score determination were performed in age and sex-matched young lean Alms1foz/foz mice and wildtype littermates.
When compared to wildtype mice, young Alms1foz/foz mice had a significantly reduced response to insulin during ITT while no differences were observed in glucose and endogenous insulin levels during GTT. Male but not female Alms1foz/foz mice had significantly higher fasting hyperinsulinemia and HOMA-IR scores compared to wildtype littermates.
These data indicate that insulin resistance precedes obesity in young Alms1foz/foz mice at a time that beta-cell function isn’t affected. This suggests that early peripheral insulin resistance is an inherent primary consequence of the Alms1foz/foz mutation and may thereby drive the subsequent metabolic complications in this model.
This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.