NODk mice is protected from T1D due to congenic replacement of Idd1 MHC locus with an autoimmune diabetes-resistant H2k locus. However, male NODk mice fed a western-diet (WD) develop a type 2 diabetes (T2D) like phenotype characterised by weight gain, dyslipidaemia, hyperinsulinaemia, and severe hyperglycaemia.

To determine if time-restricted nutrient supply, via intermittent fasting (IF) regimen, can prevent development of hyperinsulinaemia, excessive weight gain, glucose intolerance and reduce incidence of diabetes in WD fed male NODk mice.

Methods: Male NODk mice were randomised to chow diet (CD), WD or WD with IF (WD+IF) from 6 weeks until 10 or 30 weeks of age. Their metabolic characteristics were assessed, including intraperitoneal glucose tolerance testing (ipGTT) after 3 and 17 weeks on diet, and incidence of diabetes after 24 weeks on diet.

IF attenuated WD-induced body weight (24 weeks on diet (meanSEM); 38.3±0.6, 51.4±0.7, 47.0±0.5 g; CD, WD, WD+IF, respectively; diet effect p<0.0001), prevented WD-induced glucose intolerance (ipGTT glucose AUCGlu; 1016±45, 2230±127, 1433±56, mM*min; diet effect p<0.0001); and prevented WD-induced hypertriglyceridaemia (124±25, 432±46, 216±24 mg/dL; diet effect p<0.0001). WD-induced hyperinsulinaemia (fed-state; 22.7±1.4 vs 14.3±0.5 ng/mL; WD, WD+IF; p<0.05), and during ipGTT (ipGTT insulin AUCIns after 17 weeks on diet; 35425 vs 25129 ng/ml*min; WD, WD+IF; p<0.05) was attenuated. IF prevented WD-induced diabetes after 24 weeks (diabetes in 0%, 81%, 0%, respectively; p<0.0001).

IF attenuated WD-induced weight gain, hyperinsulinaemia, hypertriglyceridaemia, glucose intolerance, and prevented diabetes in WD fed NODk mice.

 

These results suggest IF to be a promising nutrient deprivation approach for prevention and treatment of T2D


Muhammad Shamoon1,2, Jane Dahlstrom3, Viviane Delghingaro-Augusto4, Christopher Nolan1,2,5
 
 

1.     School of Medicine and Psychology, The Australian National University, Acton, ACT 2600 

2.     Division of Immunology and Infectious Diseases, John Curtin School of Medical Research, The Australian National University, ACT, 2600

3.     Department of Anatomical Pathology, ACT Pathology, Canberra Health Services, Garran, ACT 2605

4.     Division of Genome Science and Cancer, John Curtin School of Medical Research, Australian National University, Canberra ACT 2600, Australia

5.     Endocrinology and Diabetes, Canberra Health Services, Garran, ACT 2605