We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Diabetes associated metabolomic perturbations in NOD mice.
- Authors
Grapov, Dmitry; Fahrmann, Johannes; Hwang, Jessica; Poudel, Ananta; Jo, Junghyo; Periwal, Vipul; Fiehn, Oliver; Hara, Manami
- Abstract
Non-obese diabetic (NOD) mice are a widely-used model of type 1 diabetes (T1D). However, not all animals develop overt diabetes. This study examined the circulating metabolomic profiles of NOD mice progressing or not progressing to T1D. Total beta-cell mass was quantified in the intact pancreas using transgenic NOD mice expressing green fluorescent protein under the control of mouse insulin I promoter. While both progressor and non-progressor animals displayed lymphocyte infiltration and endoplasmic reticulum stress in the pancreas tissue, overt T1D did not develop until animals lost ~70 % of the total beta-cell mass. Gas chromatography time of flight mass spectrometry was used to measure >470 circulating metabolites in male and female progressor and non-progressor animals (n = 76) across a wide range of ages (neonates to >40-week). Statistical and multivariate analyses were used to identify age and sex independent metabolic markers which best differentiated progressor and non-progressor animals' metabolic profiles. Key T1D-associated perturbations were related with: (1) increased plasma glucose and reduced 1,5-anhydroglucitol markers of glycemic control; (2) increased allantoin, gluconic acid and nitric acid-derived saccharic acid markers of oxidative stress; (3) reduced lysine, an insulin secretagogue; (4) increased branched-chain amino acids, isoleucine and valine; (5) reduced unsaturated fatty acids including arachidonic acid; and (6) perturbations in urea cycle intermediates suggesting increased arginine-dependent NO synthesis. Together these findings highlight the strength of the unique approach of comparing progressor and non-progressor NOD mice to identify metabolic perturbations involved in T1D progression.
- Subjects
ANIMAL models of diabetes; METABOLOMICS; TYPE 1 diabetes; ALLANTOIN; OXIDATIVE stress; DISEASE progression; METABOLIC profile tests; BIOMARKERS
- Publication
Metabolomics, 2015, Vol 11, Issue 2, p425
- ISSN
1573-3882
- Publication type
Article
- DOI
10.1007/s11306-014-0706-2