Dipeptidyl peptidase-4 inhibitor MK-626 restores insulin secretion through enhancing autophagy in high fat diet-induced mice

Biochemical and Biophysical Research Communications
Limei LiuXiaoxing Yu

Abstract

Autophagy is cellular machinery for maintenance of β-cell function and mass. The current study aimed to investigate the regulatory effects of MK-626, a dipeptidyl peptidase-4 inhibitor, on insulin secretion through the activation of autophagy in high fat diet-induced obese mice. C57BL/6 mice were fed with a rodent diet containing 45 kcal% fat for 16 weeks to induce obesity and then were received either vehicle or MK-626 (3 mg/kg/day) orally during the final 4 weeks. Mouse islets were isolated. Phosphorylation of serine/threonine-protein kinase mTOR and levels of light chain 3B I (LC3B I), LC3B II, sequestosome-1 (SQSTM1/p62) and autophagy-related protein-7 (Atg7) were examined by Western blotting. Glucagon like-peptide-1 (GLP-1) level and insulin secretion were measured by ELISA. GLP-1 level in plasma was decreased in obese mice, which was elevated by dipeptidyl peptidase-4 inhibitor MK-626. In the islets of obese mice, phosphorylation of mTOR, ratio of LC3B I and LC3B II, and level of p62 were elevated and the expression of Atg7 and insulin secretion were reduced compared to those of C57BL/6 mice. However, such effects were reversed by MK-626. Autophagy activator rapamycin stimulated insulin secretion in obese mice but autopha...Continue Reading

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Citations

Apr 5, 2018·Endocrinology·Michelle R Marasco, Amelia K Linnemann
Jan 16, 2019·Aging Cell·Biao ZhuGuangda Xiang
Feb 12, 2017·Clinical Science·Bárbara MaizteguiJuan J Gagliardino
Sep 27, 2018·Cells·Manon Moulis, Cecile Vindis
Apr 25, 2018·Nature Reviews. Endocrinology·Yingmei ZhangJun Ren
Aug 6, 2019·Journal of Molecular Biology·Kevin VivotRomeo Ricci
Feb 12, 2021·The Journal of Clinical Endocrinology and Metabolism·Kaitlin M Love, Zhenqi Liu
Jun 3, 2021·International Journal of Molecular Sciences·Safia CostesMagalie A Ravier
Sep 12, 2021·Nature Reviews. Endocrinology·Munehiro Kitada, Daisuke Koya

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