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Papers of the Week

Papers: 18 May 2024 - 24 May 2024

2024 May 22



Loss of ATP-sensitive potassium channel expression and function in the nervous system decreases opioid sensitivity in high-fat-diet-fed mouse model of diet-induced obesity.


Fisher C, Johnson K, Moore M, Sadrati A, Janecek JL, Graham ML, Klein AH


During diabetes progression, β-cell dysfunction due to loss of potassium channels sensitive to ATP, known as KATP channels, occurs contributing to hyperglycemia. The aim of this study is to investigate if KATP channel expression or activity in the nervous system was altered in a high-fatdiet-( HFD) fed mouse model of diet-induced obesity. Expression of two KATP channel subunits, Kcnj11 (Kir6.2) and Abcc8 (SUR1), were decreased in the peripheral and central nervous system in HFD mice, which is significantly correlated with mechanical paw withdrawal thresholds. HFD mice had decreased antinociception to systemic morphine compared to control diet (CON) mice, which was expected as KATP channels are downstream targets of opioid receptors. Mechanical hypersensitivity in HFD mice was exacerbated after systemic treatment with glyburide or nateglinide, KATP channel antagonists clinically used to control blood glucose levels. Upregulation of SUR1 and Kir6.2, through an adenovirus delivered intrathecally, increased morphine antinociception in HFD mice,. These data present a potential link between KATP channel function and neuropathy during early stages of diabetes. There is a need for increased knowledge in how diabetes affects structural and molecular changes in the nervous system, including ion channels, to lead to the progression of chronic pain and sensory issues.