The Korean Journal of Physiology and Pharmacology

The Korean Society of Pharmacology (대한약리학회)
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Lithium and exercise ameliorate insulin-deficient hyperglycemia by independently attenuating pancreatic α-cell mass and hepatic gluconeogenesis

  • Su-Ryun Jung (College of Pharmacy, Keimyung University) ;
  • Ji-Hye Lee (Department of New Biology, Daegu Gyeongbuk Institute of Science and Technology (DGIST)) ;
  • Hanguk Ryu (Department of New Biology, Daegu Gyeongbuk Institute of Science and Technology (DGIST)) ;
  • Yurong Gao (Department of New Biology, Daegu Gyeongbuk Institute of Science and Technology (DGIST)) ;
  • Jaemin Lee (Department of New Biology, Daegu Gyeongbuk Institute of Science and Technology (DGIST))
  • Received : 2023.08.11
  • Accepted : 2023.11.02
  • Published : 2024.01.01
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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 exercise-induced 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.

Keywords

Acknowledgement

This study was supported by the DGIST R&D Program and Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science and ICT and Ministry of Education to S.-R.J. (NRF-2020S1A5A2A01045700), J.L. (NRF-2020M3A9D8038660, 23-CoE-BT-04), and J.-H.L. (NRF-2019R1A6A3A01094138).

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