Fig. 3

Central regulation of glucose homeostasis. Changes of the blood glucose level (i.e., hypoglycemia or hyperglycemia) is detected by peripheral glucose sensors in hepatic portal vein and gastrointestinal tract (GI tract), as well as glucose-sensing neurons in the acute nucleus of hypothalamus-median eminence (ARH-ME), and area postrema (AP) and nucleus of the solitary (NTS) in the hindbrain (blue arrows), where the blood brain barrier (BBB) is permeable. Then these afferent signals are transmitted to the ventromedial hypothalamic nucleus (VMH) or other glucose-responsive regions in the brain (black arrows in the brain) where they are integrated to mount the efferent responses to restore euglycemia. Maintenance of blood glucose level is achieved by balancing entry of glucose into blood vessels, and glucose uptake by peripheral tissues (e.g., adipose tissue and muscle). Insulin is secreted from pancreatic β-cells in response to a high circulating glucose level, which promotes glucose uptake into adipose tissue and muscle, and inhibits glucose production in the liver (black arrows) via suppression of glucagon from α-cells. In the context of hypoglycemia, counterregulatory hormones—glucagon from pancreatic α-cells and catecholamines from adrenal gland are released to promote hepatic glucose production, thereby increasing glucose entry into the blood vessels. At the same time, glucose removal from blood vessels via glucose uptake is inhibited. The brain is able to balance glucose entry and uptake via autonomic nervous system (both sympathetic and parasympathetic nervous system) to reset/restore the blood glucose level to a normal range (red arrows). The figure is created in BioRender.com