Wen-Bin Lu, Yi-Shan Huang, Jian-Ching Wu, Lee-Wei Chen, I-Wen Lin, Pei-Chin Chen, Po-Han Chen, Cheng-Yi Huang, Tzu-Teng Tai, Shu-Hung Huang, Sheng-Hua Wu, Feng-Sheng Wang, Hsu-Wen Chao, Ming-Hong Tai
The exercise-induced hormone irisin plays an important role in the regulation of glucose homeostasis; however, its underlying mechanisms under insulin-deficient conditions remain unclear. We investigated whether irisin can directly regulate hepatic glucose metabolism and manage diabetic phenotypes in insulin-deficient Akita mice. Irisin improved diabetic phenotypes and was associated with enhanced glucose uptake (peroxisome proliferator-activated receptor-γ/GLUT2/GCK axis), increased glycogen storage (GSK-3β-dependent and GSK-3β-independent pathways), and reduced gluconeogenic activity, accompanied by increased AMPK phosphorylation independently of increases in insulin levels. These findings identify irisin as an insulin-independent regulator in hepatic glucose metabolism and suggest a potential therapeutic strategy for insulin-deficient diabetes.