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.
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 humanneonatal 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.
Authors: Zihan Yan; Manuela Fortunato; Zeenat A Shyr; Amy L Clark; Matt Fuess; Colin G Nichols; Maria S Remedi Journal: Diabetes Date: 2022-06-01 Impact factor: 9.337
Authors: Amy L Clark; Zihan Yan; Sophia X Chen; Victoria Shi; Devesha H Kulkarni; Abhinav Diwan; Maria S Remedi Journal: Diabetes Obes Metab Date: 2021-08-02 Impact factor: 6.408