Figure 2.

Pathways for hypoglycemia activation of the sympathetic nerve. Glucose‐sensing neurons that transmit hypoglycemia signals to the sympathetic nerve are located in the brainstem and the hypothalamus. In the brainstem, epinephrine and norepinephrine neurons of the ventrolateral medulla (VLM) can be activated by hypoglycemia or neuroglucopenia. They activate the sympathetic glucagon response indirectly through projections to the hypothalamus or directly through connections to the intermediolateral cell column (IML). Cholecystokinin neurons of the parabrachial nucleus (PBN) send projections to the ventromedial nucleus (VMN) to control glucagon secretion, as discussed in the text. The indicated hypothalamic nuclei also contain neurons that can detect hypoglycemia and activate the sympathetic nerve either through intrahypothalamic connections to the paraventricular nucleus (PVN), which send direct projections to the IML or indirect projections through the VLM. The lateral nucleus (LH) also sends projection to the VLM and IML to control sympathetic activity. The activated sympathetic nerve stimulates epinephrine secretion from the adrenals, which increases glucagon secretion and hepatic glucose production; it activates lipolysis in adipose tissue to provide free fatty acids required to fuel hepatic neoglucogenesis; it inhibits insulin secretion and directly stimulates glucagon secretion; it also directly stimulates hepatic glucose production.