Lithium and exercise ameliorate insulin-deficient hyperglycemia by independently attenuating pancreatic α-cell mass and hepatic gluconeogenesis.

IF 1.6 4区 医学 Q3 PHARMACOLOGY & PHARMACY
Su-Ryun Jung, Ji-Hye Lee, Hanguk Ryu, Yurong Gao, Jaemin Lee
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引用次数: 0

Abstract

As in type 1 diabetes, the loss of pancreatic β-cells leads to insulin deficiency and the subsequent development of hyperglycemia. Exercise has been proposed as a viable remedy for hyperglycemia. Lithium, which has been used as a treatment for bipolar disorder, has also been shown to improve glucose homeostasis under the conditions of obesity and type 2 diabetes by enhancing the effects of exercise on the skeletal muscles. In this study, we demonstrated that unlike in obesity and type 2 diabetic conditions, under the condition of insulin-deficient type 1 diabetes, lithium administration attenuated pancreatic a-cell mass without altering insulin-secreting β-cell mass, implying a selective impact on glucagon production. Additionally, we also documented that lithium downregulated the hepatic gluconeogenic program by decreasing G6Pase protein levels and upregulating AMPK activity. These findings suggest that lithium's effect on glucose metabolism in type 1 diabetes is mediated through a different mechanism than those associated with exerciseinduced metabolic changes in the muscle. Therefore, our research presents the novel therapeutic potential of lithium in the treatment of type 1 diabetes, which can be utilized along with insulin and independently of exercise.

锂和运动可通过独立减轻胰腺α细胞质量和肝脏葡萄糖生成来改善胰岛素缺乏性高血糖症。
与 1 型糖尿病一样,胰腺 β 细胞的缺失会导致胰岛素缺乏,进而引发高血糖。运动被认为是治疗高血糖症的可行方法。锂已被用作治疗躁郁症的药物,也已被证明可通过增强运动对骨骼肌的影响来改善肥胖和 2 型糖尿病患者的葡萄糖稳态。在这项研究中,我们发现与肥胖症和 2 型糖尿病不同,在胰岛素缺乏的 1 型糖尿病条件下,锂能减少胰腺 a 细胞的数量,而不改变分泌胰岛素的 β 细胞的数量,这意味着锂对胰高血糖素的产生有选择性的影响。此外,我们还发现,锂通过降低 G6Pase 蛋白水平和上调 AMPK 活性,下调了肝糖原生成程序。这些研究结果表明,锂对 1 型糖尿病患者糖代谢的影响是通过不同的机制介导的,与运动诱导肌肉代谢变化的机制不同。因此,我们的研究展示了锂在治疗 1 型糖尿病方面的新的治疗潜力,它可以与胰岛素一起使用,而不依赖于运动。
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来源期刊
Korean Journal of Physiology & Pharmacology
Korean Journal of Physiology & Pharmacology PHARMACOLOGY & PHARMACY-PHYSIOLOGY
CiteScore
3.20
自引率
5.00%
发文量
53
审稿时长
6-12 weeks
期刊介绍: The Korean Journal of Physiology & Pharmacology (Korean J. Physiol. Pharmacol., KJPP) is the official journal of both the Korean Physiological Society (KPS) and the Korean Society of Pharmacology (KSP). The journal launched in 1997 and is published bi-monthly in English. KJPP publishes original, peer-reviewed, scientific research-based articles that report successful advances in physiology and pharmacology. KJPP welcomes the submission of all original research articles in the field of physiology and pharmacology, especially the new and innovative findings. The scope of researches includes the action mechanism, pharmacological effect, utilization, and interaction of chemicals with biological system as well as the development of new drug targets. Theoretical articles that use computational models for further understanding of the physiological or pharmacological processes are also welcomed. Investigative translational research articles on human disease with an emphasis on physiology or pharmacology are also invited. KJPP does not publish work on the actions of crude biological extracts of either unknown chemical composition (e.g. unpurified and unvalidated) or unknown concentration. Reviews are normally commissioned, but consideration will be given to unsolicited contributions. All papers accepted for publication in KJPP will appear simultaneously in the printed Journal and online.
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