Involvement of Nesfatin-1/NUCB2 in the Arcuate Nucleus in Glucose homeostasis
Máté Durst1, Rita Matuska2, Péter Várnai2, Eszter Soltész-Katona2, Miklós Geiszt2, Zsuzsanna E. Tóth1
Nesfatin-1, the secreted fragment of nucleobindin’2 (NUCB2) protein was identified as an anorexigen neurotransmitter. It is widely expressed in the brain including the arcuate nucleus (Arc). Both nesfatin-1 and the Arc have recently been linked to the central regulation of the glucose homeostasis, however the exact physiological role of nesfatin-1/NUCB2 of arcuate origin is not known. In the present study, we elevated or silenced the expression of nesfatin-1/NUCB2 within the Arc in different groups of rats using synapsin promoter-driven NUCB2 overexpressing, or Sh-RNA expressing AAV9 vectors respectively, with appropriate controls. After recovery, the bodyweights were recorded regularly. To assess regulation of the blood glucose level, intraperitoneal glucose (ipGTT) and insulin tolerance tests (ipITT) were performed following the onset of virus expression. Shortage of nesfatin-1/NUCB2 in the Arc caused a slight, significant increase, overexpression of nesfatin-1/NUCB2 did not cause any changes in the bodyweight-gain compared to controls. Elevated and depressed nesfatin-1/NUCB2 levels in the Arc improved and worsened glucose tolerance of the animals, respectively. In harmony with this, insulin sensitivity increased with nesfatin-1/NUCB2 overexpression, while showed a tendency to decrease in rats with attenuated nesfatin-1/NUCB2 expression. Our results suggest a contributing role of nesfatin-1/NUCB2 in Arc to the central regulation of glucose homeostasis.