Glucokinase and insulin receptor in supraoptic nucleus neurons: Potential role in glucose and metabolic sensing

Oxytocin (OT) is an anorexic agent. Deficits in OT are associated with human obesity. Glucokinase (GK), a hallmark of glucose‐sensing cells, is expressed in the supraoptic nucleus (SON) of the hypothalamus, where OT and vasopressin (VP) are synthesized. Neurons in SON also express insulin receptor (Ins‐R) mRNA and protein. Ins‐R could either serve to increase glucose uptake to meet the high metabolic needs of these hormone producing cells or serve a nutrient‐sensing function. Therefore, SON neurons may function as both glucose‐sensors and metabolic sensors. We used live‐cell calcium imaging to determine if glucose and/or insulin altered intracellular calcium ([Ca ++ ] i ) signaling in SON neurons. Hypothalamic explants that include SON were loaded with the calcium sensitive dye, Fura‐2AM. Changes in [Ca ++ ] i were monitored by changes in the 340/380 emission in response to an increase in the glucose concentration from 0.1 to 5 mM in the absence or presence of insulin (3 ng/ml). This increment in glucose caused a transient increase in [Ca ++ ] i in a subset of SON neurons. The response was not altered by the presence of insulin. To identify the peptidergic phenotype of the responsive neurons, their responses to OT and VP were examined. The majority of the glucose‐responsive neurons responded to both OT and VP. These findings are consistent with a subset of SON OT neurons functioning as glucose‐sensors. Supported by NIH RO1 27975.