Endocrinology and Diabetes Research Unit, Medical School, The Australian National University, Canberra ACT, Australia (firstname.lastname@example.org)
Introduction: NODk mice are congenic for the protective MHC H2k (Idd 1 locus) and unlike NOD mice do not develop autoimmune diabetes. The aim of the study was determine if NODk β-cells have a non-immune islet b-cell defect that may be revealed by stressing the islets with a high fat diet. B10.Br and Balb/c mice were used as comparator groups.
Method: Male NODk, B10.Br and Balb/c mice (6-11 mice per group) were fed chow or high fat (HF) diets from 4 weeks of age for 10 weeks (short-term) and 20 weeks (long-term) study. Body weight and blood glucose were measured fortnightly. At 13 and 23 weeks of age intraperitoneal glucose tolerance tests (ipGTT) were performed for the short-term and long-term study mice, respectively. Intraperitoneal insulin tolerance tests (ipITT) were also performed at 13 weeks of age in the long-term study. At sacrifice, the pancreas was harvested for histological assessment.
Results: Despite excellent glucose tolerance at all ages on chow diet, high fat-fed NODk mice developed diet-induced obesity, profound hyperinsulinaemia and diabetes by 13 weeks of age. Due to severe hyperglycaemia several NODk mice needed to be euthanased prior to completing the long-term study. B10.Br mice had poor glucose tolerance on chow diet only, but despite some HF diet induced excessive weight gain, they did not develop severe hyperinsulinaemia or progress onto diabetes. Balb/c mice maintained excellent glucose tolerance on both diets. Preliminary analyses of the pancreas histology does not indicate that the diabetes in the HF fed NODk mice is due to insulitis.
Conclusion: The results indicate that NODk mice are prone to a severe type 2 diabetes phenotype when fed a HF diet. Underlying non-immune islet susceptibility factors may contribute to the propensity of NOD mice to type 1 diabetes and the NODk mice to type 2 diabetes.