Glucose responsive neurons in the nucleus of the solitary tract are responsive to nesfatin‐1 (1126.3)

Nesfatin‐1 (nes‐1) exerts important effects on food intake and glucose handling and is expressed in the nucleus of the solitary tract (NTS), a critical medullary autonomic control center. Since hypoglycemia induces cFos expression in nes‐1 immunoreactive NTS neurons, here we examined effects of nes‐1 on the excitability of glucose responsive NTS cells using whole‐cell patch clamp recordings. A total of 44% of neurons tested (7/16) responded to a decrease from 3 to 0.2 mM glucose, 4 with a depolarization (glucose inhibited (GI), mean 6.1 ± 1.6 mV), and 3 with a hyperpolarization (glucose excited (GE), mean ‐5.7 ± 1.4 mV). Bath applied nes‐1 (10 nM) influenced the excitability of all but one of these glucose responsive neurons. All GI neurons responded to nes‐1, 3 with a depolarization (mean 7.6 ± 2.4 mV) and 1 with a hyperpolarization (‐8.5 mV). Moreover, 2/3 GE cells were depolarized by nes‐1 (mean 3.3 ± 1.0 mV) while 1 did not respond. NTS neurons which did not respond to changes in glucose (9/16) were also nes‐1 responsive, with 5 showing a depolarization (mean 3.5 ± 0.4 mV) and 4 a hyperpolarization (mean ‐5.8 ± 0.5 mV). While our findings reveal clear actions of nes‐1 on glucose sensing NTS neurons, they do not suggest functional differentiation between the effects of nes‐1 on GI and GE neurons. Our observations lend further support to the hypothesis that nes‐1 may act as a locally released modulator of intrinsic neuronal function. Grant Funding Source : NSERC, FQRNT, HSFO