Glucose in the hypothalamic paraventricular nucleus regulates GLP-1 release

• DOI: 10.1172/jci.insight.132760
• Publication Date: 2020-03-31T16:17:54Z
• Authors: Yue Ma; Risheka Ratnasaba...; Ivan De Backer; Chioma Izzi-Engbeaya; Marie-Sophie Nguy...; Joyceline Cuenco; Ben Jones; Christopher D. John; Brian Y.H. Lam; Guy A. Rutter; Giles S.H. Yeo; Waljit S. Dhillo; James Gardiner
• Keywords: Male; HOMEOSTASIS; Rats, Inbred WF; Research & Experimental Medicine; NEUROTRANSMITTERS; RATS; 03 medical and health sciences; Endocrinology; Glucagon-Like Peptide 1; STIMULATES GLP-1; Glucokinase; Animals; BRAIN; Glucose metabolism; 0303 health sciences; Science & Technology; PURIFICATION; PEPTIDE-1 SECRETION; Research & Experimental; Diabetes; Rats; Glucose; Medicine, Research & Experimental; CELLS; Medicine; GIP SECRETION; Peptides; Life Sciences & Biomedicine; GLUCOKINASE; Research Article; Neuroscience; Paraventricular Hypothalamic Nucleus

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.