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

Abstract

As in type 1 diabetes, the loss of pancreatic β-cell leads to insulin deficiency and eventual hyperglycemia. Exercise has been suggested 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 condition 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 attenuated glucagon-producing pancreatic α-cell mass and downregulated hepatic gluconeogenic program by decreasing G6Pase protein levels and upregulating AMPK activity rather than promoting the metabolic effect of an exercise on the muscle. Thus, our research demonstrates the new therapeutic potential of lithium for type 1 diabetes, which can be utilized independently of exercise.