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Using fasted RIPGLUT1 \u00d7 GLUT2\u2212\/\u2212 mice, we showed that glucagonemia was no longer increased by hypoglycemic (2.5 mmol\/l glucose) clamps or suppressed by hyperglycemic (10 and 20 mmol\/l glucose) clamps. However, an increase in plasma glucagon levels was detected when glycemia was decreased to \u22641 mmol\/l, indicating preserved glucagon secretory ability, but of reduced sensitivity to glucopenia. To evaluate whether the high-fed glucagonemia could be due to an abnormally increased tone of the autonomic nervous system, fed mutant mice were injected with the ganglionic blockers hexamethonium and chlorisondamine. Both drugs lead to a rapid return of glucagonemia to the levels found in control fed mice. We conclude that 1) in the absence of GLUT2, there is an impaired control of glucagon secretion by low or high glucose; 2) this impaired glucagon secretory activity cannot be due to absence of GLUT2 from \u03b1-cells because these cells do not normally express this transporter; 3) this dysregulation may be due to inactivation of GLUT2-dependent glucose sensors located outside the endocrine pancreas and controlling glucagon secretion; and 4) because fed hyperglucagonemia is rapidly reversed by ganglionic blockers, this suggests that in the absence of GLUT2, there is an increased activity of the autonomic nervous system stimulating glucagon secretion during the fed state.<\/jats:p>","DOI":"10.2337\/diabetes.50.6.1282","type":"journal-article","created":{"date-parts":[[2007,3,6]],"date-time":"2007-03-06T19:04:22Z","timestamp":1173207862000},"page":"1282-1289","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":60,"title":["Evidence That Extrapancreatic GLUT2-Dependent Glucose Sensors Control Glucagon Secretion"],"prefix":"10.2337","volume":"50","author":[{"given":"Re\u0301my","family":"Burcelin","sequence":"first","affiliation":[{"name":"Institute of Pharmacology and Toxicology, University of Lausanne, Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernard","family":"Thorens","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology and Toxicology, University of Lausanne, Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1167","reference":[{"key":"2022031207101756600_R1","doi-asserted-by":"crossref","unstructured":"Bolli G, De Feo P, Compagnucci P, Cartechini MG, Angeletti GA, Santeusanio F, Brunetti P, Gerich JE: Abnormal glucose counterregulation in insulin-dependent diabetes mellitus. 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