High-fat-diet-induced remission of diabetes in a subset of KATP-GOF insulin-secretory-deficient mice

Zihan Yan, Zeenat A. Shyr, Manuela Fortunato, Alecia Welscher, Mariana Alisio, Michael Martino, Brian N. Finck, Hannah Conway, Maria S. Remedi

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

Aims: To examine the effects of a high-fat-diet (HFD) on monogenic neonatal diabetes, without the confounding effects of compensatory hyperinsulinaemia. Methods: Mice expressing KATP channel gain-of-function (KATP-GOF) mutations, which models human neonatal diabetes, were fed an HFD. Results: Surprisingly, KATP-GOF mice exhibited resistance to HFD-induced obesity, accompanied by markedly divergent blood glucose control, with some KATP-GOF mice showing persistent diabetes (KATP-GOF-non-remitter [NR] mice) and others showing remission of diabetes (KATP-GOF-remitter [R] mice). Compared with the severely diabetic and insulin-resistant KATP-GOF-NR mice, HFD-fed KATP-GOF-R mice had lower blood glucose, improved insulin sensitivity, and increased circulating plasma insulin and glucagon-like peptide-1 concentrations. Strikingly, while HFD-fed KATP-GOF-NR mice showed increased food intake and decreased physical activity, reduced whole body fat mass and increased plasma lipids, KATP-GOF-R mice showed similar features to those of control littermates. Importantly, KATP-GOF-R mice had restored insulin content and β-cell mass compared with the marked loss observed in both HFD-fed KATP-GOF-NR and chow-fed KATP-GOF mice. Conclusion: Together, our results suggest that restriction of dietary carbohydrates and caloric replacement by fat can induce metabolic changes that are beneficial in reducing glucotoxicity and secondary consequences of diabetes in a mouse model of insulin-secretory deficiency.

Original languageEnglish
Pages (from-to)2574-2584
Number of pages11
JournalDiabetes, Obesity and Metabolism
Volume20
Issue number11
DOIs
StatePublished - Nov 2018

Keywords

  • glucose metabolism
  • high fat diet
  • insulin resistance
  • insulin secretion
  • islets
  • β-cell function

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