Astrocytes in systemic regulation of blood glucose and the development of type 2 diabetes

The central nervous system (CNS) relies primarily on glucose for energy, and therefore maintaining peripheral glucose homeostasis is essential to ensure adequate CNS energy supply and normal physiological functions. Historically, hypothalamic neurons-particularly defined glucose-sensing neuronal populations-were considered the main sensors and regulators of systemic glucose, while astrocytes primarily serving a nutritional and supportive role for neurons. However, recent studies have progressively revealed that astrocytes also play a significant role in systemic glucose regulation, particularly within the hypothalamus. In this review, we discuss the molecular mechanisms by which hypothalamic astrocytes sense glucose and modulate glucose homeostasis, and we examine how astrocyte-neuron interactions cooperate to maintain systemic glucose balance. We also summarize evidence that astrocytes in other regions, such as the hindbrain, participate in glucose regulation. Finally, we consider how altered astrocyte function may contribute to the development and progression of type 2 diabetes through changes in metabolism and inflammatory or signaling pathways. Research in this field not only expands our understanding of glial cell functions in metabolic regulation but also provides novel potential intervention targets for diseases associated with energy homeostasis imbalance, such as diabetes.