Glucose in the hypothalamic paraventricular nucleus regulates GLP-1 release.
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Glucokinase (GK) is highly expressed in the hypothalamic paraventricular nucleus (PVN); however, its role is currently unknown. We found that GK in the PVN acts as part of a glucose-sensing mechanism within the PVN that regulates glucose homeostasis by controlling glucagon-like peptide 1 (GLP-1) release. GLP-1 is released from enteroendocrine L cells in response to oral glucose. Here we identify a brain mechanism critical to the release of GLP-1 in response to oral glucose. We show that increasing expression of GK or injection of glucose into the PVN increases GLP-1 release in response to oral glucose. On the contrary, decreasing expression of GK or injection of nonmetabolizable glucose into the PVN prevents GLP-1 release. Our results demonstrate that gluco-sensitive GK neurons in the PVN are critical to the response to oral glucose and subsequent release of GLP-1.
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2379-3708
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Wellcome Trust (100574/Z/12/Z)
Medical Research Council (MC_UU_12012/1)
Medical Research Council (MC_UU_12012/5)
MRC (MC_UU_00014/5)
MRC (MR/S026193/1)
Biotechnology and Biological Sciences Research Council (BB/S017593/1)
Medical Research Council (MC_PC_12012)