Interaction of B0AT1 deficiency and diet on metabolic function and diabetes incidence in male NOD mice
Matthew F Waters, Viviane Delghingaro-Augusto, Muhammad Shamoon, Kiran Javed, Gaetan Burgio, Jane E Dahlstrom, Stefan Bröer, Christopher J NolanAbstract
Context
The obesity epidemic parallels an increasing type 1 diabetes incidence, such that westernized diets, containing high fat, sugar and/or protein, through inducing nutrient-induced islet beta-cell stress, have been proposed as contributing factors. The broad-spectrum neutral amino acid transporter (B0AT1), encoded by Slc6a19, is the major neutral amino acids transporter in intestine and kidney. B0AT1 deficiency in C567Bl/6J mice, causes aminoaciduria, lowers insulinemia and improves glucose tolerance.
Objective
We investigated the effects of standard rodent chow (Chow), high-fat high-sucrose (HFHS) and high-fat high-protein (HFHP) diets, in addition to B0AT1 deficiency, on the diabetes incidence of male non-obese diabetic (NOD/ShiLtJArc (NOD)) mice.
Results
The incidence of diabetes and severe glucose intolerance was 3.8% in HFHS-fed, 25.0% in HFHP-fed, and 14.7% in Chow-fed mice, with higher pancreatic islet number and lower insulitis scores in HFHS-fed mice. B0AT1 deficiency had no effect on diabetes incidence, but curtailed HFHS-induced excessive weight gain, adipose tissue expansion and hyperinsulinemia. In HFHP-fed mice, B0AT1 deficiency significantly increased pancreatic beta-cell clusters and small islets. Male NOD mice that did not develop autoimmune diabetes were resistant to diet-induced hyperglycemia.
Conclusion
Dietary composition does, but B0AT1 deficiency does not, impact autoimmune diabetes incidence in male NOD mice. B0AT1 deficiency, however, reduces diet-induced metabolic dysfunction and in HFHP fed mice increases pancreatic beta-cell clusters and small islets.