title: Nervous glucose sensing regulates postnatal β cell proliferation and glucose homeostasis.
abstract: How glucose sensing by the nervous system impacts the regulation of β cell mass and function during postnatal development and throughout adulthood is incompletely understood. Here, we studied mice with inactivation of glucose transporter 2 (Glut2) in the nervous system (NG2KO mice). These mice displayed normal energy homeostasis but developed late-onset glucose intolerance due to reduced insulin secretion, which was precipitated by high-fat diet feeding. The β cell mass of adult NG2KO mice was reduced compared with that of WT mice due to lower β cell proliferation rates in NG2KO mice during the early postnatal period. The difference in proliferation between NG2KO and control islets was abolished by ganglionic blockade or by weaning the mice on a carbohydrate-free diet. In adult NG2KO mice, first-phase insulin secretion was lost, and these glucose-intolerant mice developed impaired glucagon secretion when fed a high-fat diet. Electrophysiological recordings showed reduced parasympathetic nerve activity in the basal state and no stimulation by glucose. Furthermore, sympathetic activity was also insensitive to glucose. Collectively, our data show that GLUT2-dependent control of parasympathetic activity defines a nervous system/endocrine pancreas axis that is critical for β cell mass establishment in the postnatal period and for long-term maintenance of β cell function.
authors: David
authors: D
authors: Tarussio
authors: Salima
authors: S
authors: Metref
authors: Pascal
authors: P
authors: Seyer
authors: Lourdes
authors: L
authors: Mounien
authors: David
authors: D
authors: Vallois
authors: Christophe
authors: C
authors: Magnan
authors: Marc
authors: M
authors: Foretz
authors: Bernard
authors: B
authors: Thorens
mesh_terms: D000200:Action Potentials; D000818:Animals; D001339:Autonomic Fibers, Preganglionic / Q000502:physiology; D049109:Cell Proliferation; D004734:Energy Metabolism; D005260:Female; D005726:Ganglia, Parasympathetic / Q000378:metabolism / Q000503:physiopathology; D005947:Glucose / Q000378:metabolism*; D018149:Glucose Intolerance / Q000378:metabolism; D051273:Glucose Transporter Type 2 / Q000172:deficiency / Q000235:genetics*; D006706:Homeostasis; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010179:Pancreas / Q000294:innervation / Q000473:pathology
chemical_list: D051273:Glucose Transporter Type 2; D007328:Insulin; C495682:Slc2a2 protein, mouse; D005947:Glucose