Capsaicin sensitive afferent neurons from peripheral glucose receptors mediate the insulin-induced increase in...

The effect of insulin and of 2-deoxy-D-glucose (2-DG) on adrenaline secretion was compared in rats pretreated as neonates with capsaicin and in rats pretreated with the drug-vehicle. Capsaicin-pretreatment did not inhibit the fall in blood glucose concentrations induced by insulin or by fasting, nor did it affect the increase in blood glucose concentrations in response to 2-DG or restraint stress. Capsaicin greatly reduced the rise in urinary adrenaline excretion over 24 h and the fall in the adrenaline content of the adrenal glands normally induced by insulin. In contrast, capsaicin-pretreatment did not interfere with the rise in the adrenaline excretion and the fall in the adrenaline content of the adrenal glands normally induced by 2-DG. Insulin-induced hypoglycaemia as well as intracellular glucopenia in the brain caused by 2-DG activate hypothalamic centres which stimulate the nervous input to the adrenal medulla and adrenaline secretion. The fact that capsaicin interfered only with the adrenal effect of insulin suggests the involvement of afferent C-fibres in this insulin effect. Injection into the hepatic portal vein of a C-fibre stimulating dose of capsaicin increased arterial glucose concentrations in vehicle-pretreated rats but not in capsaicin-pretreated rats. The response was significantly diminished after bilateral vagotomy. From the present results it is concluded that glucose receptors in the hepatic portal vein transmit signals via afferent, capsaicin sensitive C-fibres to the brain and that activation of this pathway is essential for the increase in adrenaline secretion elicited by insulin-induced hypoglycaemia.