Article: article from journal or magazin.
Evidence from glut2-null mice that glucose is a critical physiological regulator of feeding.
A role for glucose in the control of feeding has been proposed, but its precise physiological importance is unknown. Here, we evaluated feeding behavior in glut2-null mice, which express a transgenic glucose transporter in their beta-cells to rescue insulin secretion (ripglut1;glut2-/- mice). We showed that in the absence of GLUT2, daily food intake was increased and feeding initiation and termination following a fasting period were abnormal. This was accompanied by suppressed regulation of hypothalamic orexigenic and anorexigenic neuropeptides expression during the fast-to-refed transition. In these conditions, however, there was normal regulation of the circulating levels of insulin, leptin, or glucose but a loss of regulation of plasma ghrelin concentrations. To evaluate whether the abnormal feeding behavior was due to suppressed glucose sensing, we evaluated feeding in response to intraperitoneal or intracerebroventricular glucose or 2-deoxy-D-glucose injections. We showed that in GLUT2-null mice, feeding was no longer inhibited by glucose or activated by 2-deoxy-D-glucose injections and the regulation of hypothalamic neuropeptide expression by intracerebroventricular glucose administration was lost. Together, these data demonstrate that absence of GLUT2 suppressed the function of central glucose sensors, which control feeding probably by regulating the hypothalamic melanocortin pathway. Furthermore, inactivation of these glucose sensors causes overeating.
Animals, Base Sequence, DNA Primers, Feeding Behavior/physiology, Ghrelin, Glucose Transporter Type 2/deficiency, Glucose Transporter Type 2/genetics, Hypothalamus/physiology, Insulin/blood, Leptin/blood, Mice, Mice, Inbred C57BL, Mice, Knockout, Neuropeptides/genetics, Peptide Hormones/blood, Pro-Opiomelanocortin/genetics, RNA, Messenger/genetics, RNA, Messenger/isolation & purification, Reverse Transcriptase Polymerase Chain Reaction, alpha-MSH/physiology
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