Leptin increases KATP channels’ surface expression of GT1-7 cells to regulate low glucose response

Abstract

Glucose-sensing neurons in the hypothalamus play a pivotal role in maintaining glucose homeostasis in vivo and in detecting hypoglycemia. Leptin, a key hormone regulating body weight and energy balance, has been shown to modulate these glucose-sensing neurons, thereby enhancing glucose uptake. However, the precise mechanism by which leptin regulates K
ATP
channels to influence glucose responsiveness remains unclear. In this study, we employed a comprehensive approach combining electrophysiological techniques, biotinylation assays, and immunofluorescence—using the GT1-7 mouse hypothalamic cell line to elucidate this mechanism. We found that leptin enhances K
ATP
channel currents, resulting in hyperpolarization. This effect is attributable to the increased surface expression of the SUR1 subunit of K
ATP
channels. Importantly, leptin receptors are required in whole process. Consequently, leptin alters the glucose responsiveness of GT1-7 cells by modulating the surface expression of K
ATP
channels and enhancing their activity.