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Original Article

Korean J Physiol Pharmacol 2024; 28(1): 31-38

Published online January 1, 2024 https://doi.org/10.4196/kjpp.2024.28.1.31

Copyright © Korean J Physiol Pharmacol.

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

Su-Ryun Jung1,2,*, Ji-Hye Lee3,4, Hanguk Ryu3, Yurong Gao3, and Jaemin Lee3,4,5,*

1College of Pharmacy, Keimyung University, Daegu 42601, 2Senotherapy-based Metabolic Disease Control Research Center, Yeungnam University, Daegu 42415, 3Department of New Biology, 4New Biology Research Center, 5Well Aging Research Center, Daegu Gyeongbuk Institute of Science and Technology (DGIST), Daegu 42988, Korea

Correspondence to:Su-Ryun Jung
E-mail: susu73@yu.ac.kr
Jaemin Lee
E-mail: jaeminlee@dgist.ac.kr

Author contributions: S.R.J. conducted animal experiments and Western blotting, and J.H.L., H.R., and Y.G. analyzed blood insulin levels, islet histology, and its quantification. S.R.J. and J.L. examined the experimental data, wrote the manuscript, and conceptualized and supervised the study.

Received: August 11, 2023; Revised: October 22, 2023; Accepted: November 2, 2023

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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.

Keywords: Diabetes mellitus, type 1, Exercise, Glucagon-secreting cells, Gluconeogenesis, Lithium