Glucoprivation of hypothalamic neurons elicits the counter‐regulatory response in rats

Abstract

Whether the sympathetic counter‐regulatory response to hypoglycaemia is activated by glucose sensing neurons in the fore‐or hind‐brain remains controversial, since systemic hypoglycaemia excites neurons located in both areas. Here, we hypothesize that neurons in the perifornical hypothalamus (PeH), but not in the rostral ventrolateral medulla (RVLM), sense the reduction in glycaemia and increase the adrenal sympathetic nerve activity (ASNA). Experiments were conducted in anaesthetized (urethane, 1.2 g/kg i.v.), paralysed (pancuronium bromide, 1 mg/kg i.v.), and artificially ventilated male Sprague‐Dawley rats. Local glucopaenia, induced by bilateral microinjections of 2‐deoxy‐D‐glucose (2DG; 15 ng/50 nl) into the PeH, increased ASNA (101±1% vs 175±11%, N=10; P<0.05) and blood glucose (6.6±0.3 vs 7.6±0.3 mmol/l, N=9; P<0.05). A higher dose of 2DG (150 ng/50 nl) further increased ASNA (157±7% vs 280±59%, N=6; P<0.05) and blood glucose (7.5±0.5 vs.9.6±0.5 mmol/l, N=4; P<0.05). Microinjections of 2DG (15 ng/50 nl) into the RVLM (N=6) neither changed ASNA (101±1% vs 84±14%) nor blood glucose (6.4±0.1 vs 6.9±0.1 mmol/l). Subsequent intravenous infusion of 2DG (250 mg/kg) increased ASNA (101±1% vs 183±8%; P<0.05). The results indicate that neurons in the PeH, but not in the RVLM, are glucose sensitive and their excitation produces adrenaline release in response to glucoprivation.