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

Autor: Yan Z; Department of Medicine, Division of Endocrinology, Metabolism and Lipid Research, Washington University School of Medicine, St Louis, Missouri., Shyr ZA; Department of Medicine, Division of Endocrinology, Metabolism and Lipid Research, Washington University School of Medicine, St Louis, Missouri., Fortunato M; Department of Medicine, Division of Endocrinology, Metabolism and Lipid Research, Washington University School of Medicine, St Louis, Missouri., Welscher A; Department of Medicine, Division of Endocrinology, Metabolism and Lipid Research, Washington University School of Medicine, St Louis, Missouri., Alisio M; Department of Medicine, Division of Endocrinology, Metabolism and Lipid Research, Washington University School of Medicine, St Louis, Missouri., Martino M; Department of Medicine, Division of Geriatrics and Nutritional Science, Washington University School of Medicine, St Louis, Missouri., Finck BN; Department of Medicine, Division of Geriatrics and Nutritional Science, Washington University School of Medicine, St Louis, Missouri., Conway H; Department of Medicine, Division of Endocrinology, Metabolism and Lipid Research, Washington University School of Medicine, St Louis, Missouri., Remedi MS; Department of Medicine, Division of Endocrinology, Metabolism and Lipid Research, Washington University School of Medicine, St Louis, Missouri.
Jazyk: angličtina
Zdroj: Diabetes, obesity & metabolism [Diabetes Obes Metab] 2018 Nov; Vol. 20 (11), pp. 2574-2584. Date of Electronic Publication: 2018 Jul 11.
DOI: 10.1111/dom.13423
Abstrakt: 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 K ATP channel gain-of-function (K ATP -GOF) mutations, which models human neonatal diabetes, were fed an HFD.
Results: Surprisingly, K ATP -GOF mice exhibited resistance to HFD-induced obesity, accompanied by markedly divergent blood glucose control, with some K ATP -GOF mice showing persistent diabetes (K ATP -GOF-non-remitter [NR] mice) and others showing remission of diabetes (K ATP -GOF-remitter [R] mice). Compared with the severely diabetic and insulin-resistant K ATP -GOF-NR mice, HFD-fed K ATP -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 K ATP -GOF-NR mice showed increased food intake and decreased physical activity, reduced whole body fat mass and increased plasma lipids, K ATP -GOF-R mice showed similar features to those of control littermates. Importantly, K ATP -GOF-R mice had restored insulin content and β-cell mass compared with the marked loss observed in both HFD-fed K ATP -GOF-NR and chow-fed K ATP -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.
(© 2018 John Wiley & Sons Ltd.)
Databáze: MEDLINE
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