Negative Effects of Cyclic Palmitate Treatment on Glucose Responsiveness and Insulin Production in Mouse Insulinoma Min6 Cells Are Reversible

内科学 内分泌学 葡萄糖激酶 生物 胰岛素瘤 胰岛素 PDX1型 体内 下调和上调 小岛 医学 基因 生物化学 生物技术
作者
Yuanyuan Nie,Jiaxuan Li,Yan Jin,B. L. Grégoire Nyomba,Peter A. Cattini,Hana Vakili
出处
期刊:DNA and Cell Biology [Mary Ann Liebert, Inc.]
卷期号:38 (4): 395-403
标识
DOI:10.1089/dna.2018.4558
摘要

Pancreatic β-cell failure is characterized by compromised insulin secretion in response to glucose, which ultimately results in hyperglycemia, the clinical hallmark of type 2 diabetes mellitus (T2DM). Acute exposure to plasma free fatty acids (FFAs) potentiates glucose stimulated insulin secretion (GSIS), while chronic exposure impairs GSIS, and the latter has been associated with the mechanism of β cell failure in obesity linked T2DM. By contrast, growth hormone (GH) signaling has been linked positively to GSIS in β cells. Numerous studies have examined chronic exposure of β cells to elevated FFAs both with in vivo cohorts and in vitro models. Little attention, however, has been given to the fluctuation of plasma FFA levels due to rhythmic effects that are affected by daily diet and fat intake. Mouse insulinoma Min6 cells were exposed to cyclic/daily palmitate treatment over 2 and 3 days to assess effects on GSIS. Cyclic/daily palmitate treatment with a period of recovery negatively affected GSIS in a dose-dependent manner. Removal of palmitate after two cycles/day resulted in reversal of the effect on GSIS, which was also reflected by relative gene expression involved in insulin biosynthesis (Ins1, Ins2, Pdx1, and MafA) and GSIS (glucose 2 transporter and glucokinase). Modest positive effects on GSIS and glucokinase transcript levels were also observed when Min6 cells were cotreated with human GH and palmitate. These observations indicate that like continuous palmitate treatment, cyclic exposure to palmitate can acutely impair GSIS over 48 and 72 h. However, they also suggest that the negative effects of short periods of exposure to FFAs on β cell function remain reversible.
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