{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T15:10:48Z","timestamp":1784733048494,"version":"3.55.0"},"reference-count":60,"publisher":"American Diabetes Association","issue":"5","license":[{"start":{"date-parts":[[2021,9,8]],"date-time":"2021-09-08T00:00:00Z","timestamp":1631059200000},"content-version":"vor","delay-in-days":3067,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/3.0\/"}],"content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2013,5,1]]},"abstract":"<jats:p>Type 2 diabetes (T2D) is characterized by \u03b2-cell dysfunction and the subsequent depletion of insulin production, usually in a context of increased peripheral insulin resistance. T2D patients are routinely treated with oral antidiabetic agents such as sulfonylureas or dipeptidyl peptidase-4 antagonists, which promote glucose- and incretin-dependent insulin secretion, respectively. Interestingly, insulin secretion may also be induced by neural stimulation. Here we report the expression of Nogo-A in \u03b2-cells. Nogo-A is a membrane protein that inhibits neurite outgrowth and cell migration in the central nervous system. We observed that Nogo-A\u2013deficient mice display improved insulin secretion and glucose clearance. This was associated with a stronger parasympathetic input and higher sensitivity of \u03b2-cells to the cholinergic analog carbachol. Insulin secretion was also improved in diabetic db\/db mice treated with neutralizing antibody against Nogo-A. Together, these findings suggest that promoting the vagal stimulation of insulin secretion through the selective inhibition of Nogo-A could be a novel therapeutic approach in T2D.<\/jats:p>","DOI":"10.2337\/db12-0949","type":"journal-article","created":{"date-parts":[[2012,12,29]],"date-time":"2012-12-29T07:20:11Z","timestamp":1356765611000},"page":"1443-1452","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":10,"title":["Nogo-A Downregulation Improves Insulin Secretion in Mice"],"prefix":"10.2337","volume":"62","author":[{"given":"Claire B.","family":"Bonal","sequence":"first","affiliation":[{"name":"Department of Genetic Medicine and Development, Faculty of Medicine, University of Geneva, Geneva, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Delphine E.","family":"Baronnier","sequence":"additional","affiliation":[{"name":"Department of Genetic Medicine and Development, Faculty of Medicine, University of Geneva, Geneva, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Pot","sequence":"additional","affiliation":[{"name":"Division of Neurology, Department of Neurosciences, Geneva University Hospital, Geneva, Switzerland"},{"name":"Department of Pathology and Immunology, University of Geneva, Geneva, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahdia","family":"Benkhoucha","sequence":"additional","affiliation":[{"name":"Division of Neurology, Department of Neurosciences, Geneva University Hospital, Geneva, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin E.","family":"Schwab","sequence":"additional","affiliation":[{"name":"Brain Research Institute, University of Zurich, Zurich, Switzerland"},{"name":"Department of Biology, Swiss Federal Institute of Technology, Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrice H.","family":"Lalive","sequence":"additional","affiliation":[{"name":"Division of Neurology, Department of Neurosciences, Geneva University Hospital, Geneva, Switzerland"},{"name":"Department of Pathology and Immunology, University of Geneva, Geneva, Switzerland"},{"name":"Division of Laboratory Medicine, Department of Genetic and Laboratory Medicine, Geneva University Hospital, Geneva, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pedro L.","family":"Herrera","sequence":"additional","affiliation":[{"name":"Department of Genetic Medicine and Development, Faculty of Medicine, University of Geneva, Geneva, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1167","published-online":{"date-parts":[[2013,4,16]]},"reference":[{"key":"2022031303181678200_B1"},{"key":"2022031303181678200_B2","doi-asserted-by":"crossref","first-page":"1253","DOI":"10.1210\/jcem.86.3.7367","article-title":"Activation of the parasympathetic nervous system is necessary for normal meal-induced insulin secretion in rhesus macaques","volume":"86","author":"D\u2019Alessio","year":"2001","journal-title":"J Clin Endocrinol Metab"},{"key":"2022031303181678200_B3","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/0014-2999(92)90245-Y","article-title":"CCK-8-stimulated insulin secretion in vivo is mediated by CCKA receptors","volume":"213","author":"Karlsson","year":"1992","journal-title":"Eur J Pharmacol"},{"key":"2022031303181678200_B4","doi-asserted-by":"crossref","first-page":"R1449","DOI":"10.1152\/ajpregu.2000.279.4.R1449","article-title":"Portal GLP-1 administration in rats augments the insulin response to glucose via neuronal mechanisms","volume":"279","author":"Balkan","year":"2000","journal-title":"Am J Physiol Regul Integr Comp Physiol"},{"key":"2022031303181678200_B5","doi-asserted-by":"crossref","first-page":"766","DOI":"10.1055\/s-2004-826161","article-title":"Physiology of GLP-1\u2014lessons from glucoincretin receptor knockout mice","volume":"36","author":"Thorens","year":"2004","journal-title":"Horm Metab Res"},{"key":"2022031303181678200_B6","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1002\/dmrr.329","article-title":"Glucose-stimulated signaling pathways in biphasic insulin secretion","volume":"18","author":"Straub","year":"2002","journal-title":"Diabetes Metab Res Rev"},{"key":"2022031303181678200_B7","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1177\/0148607108321705","article-title":"Visceral nerves: vagal and sympathetic innervation","volume":"32","author":"Teff","year":"2008","journal-title":"JPEN J Parenter Enteral Nutr"},{"key":"2022031303181678200_B8","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1111\/j.1748-1716.1981.tb06698.x","article-title":"Nervous control of pancreatic endocrine secretion in pigs. II. The effect of pharmacological blocking agents on the response to vagal stimulation","volume":"111","author":"Holst","year":"1981","journal-title":"Acta Physiol Scand"},{"key":"2022031303181678200_B9","first-page":"R629","article-title":"Neural control of insulin secretion: interaction of norepinephrine and acetylcholine","volume":"244","author":"Campfield","year":"1983","journal-title":"Am J Physiol"},{"key":"2022031303181678200_B10","doi-asserted-by":"crossref","first-page":"885","DOI":"10.1210\/endo-123-2-885","article-title":"Effect of electrical stimulation of the vagus nerve on insulinemia and glycemia in Acomys cahirinus mice","volume":"123","author":"Ionescu","year":"1988","journal-title":"Endocrinology"},{"key":"2022031303181678200_B11","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1111\/j.1748-1716.1988.tb08311.x","article-title":"Effects of pancreatic noradrenaline infusion on basal and stimulated islet hormone secretion in the dog","volume":"132","author":"Ahr\u00e9n","year":"1988","journal-title":"Acta Physiol Scand"},{"key":"2022031303181678200_B12","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/0165-1838(92)90250-K","article-title":"Neonatal capsaicin-treatment in mice: effects on pancreatic peptidergic nerves and 2-deoxy-d-glucose-induced insulin and glucagon secretion","volume":"39","author":"Karlsson","year":"1992","journal-title":"J Auton Nerv Syst"},{"key":"2022031303181678200_B13","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1007\/BF02784941","article-title":"Neural regulation of the endocrine pancreas","volume":"18","author":"Brunicardi","year":"1995","journal-title":"Int J Pancreatol"},{"key":"2022031303181678200_B14","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1016\/0012-1606(90)90357-O","article-title":"Insulin cells of pancreas extend neurites but do not arise from the neuroectoderm","volume":"142","author":"Teitelman","year":"1990","journal-title":"Dev Biol"},{"key":"2022031303181678200_B15","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/0092-8674(88)90375-3","article-title":"On the origin of pancreatic endocrine cells","volume":"53","author":"Le Douarin","year":"1988","journal-title":"Cell"},{"key":"2022031303181678200_B16","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1677\/jme.1.01866","article-title":"Identification and characterization of a novel isoform of the vesicular gamma-aminobutyric acid transporter with glucose-regulated expression in rat islets","volume":"36","author":"Suckow","year":"2006","journal-title":"J Mol Endocrinol"},{"key":"2022031303181678200_B17","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1038\/347151a0","article-title":"Identification of the 64K autoantigen in insulin-dependent diabetes as the GABA-synthesizing enzyme glutamic acid decarboxylase","volume":"347","author":"Baekkeskov","year":"1990","journal-title":"Nature"},{"key":"2022031303181678200_B18","doi-asserted-by":"crossref","first-page":"6006","DOI":"10.1210\/en.2008-0274","article-title":"Expression of neurexin, neuroligin, and their cytoplasmic binding partners in the pancreatic beta-cells and the involvement of neuroligin in insulin secretion","volume":"149","author":"Suckow","year":"2008","journal-title":"Endocrinology"},{"key":"2022031303181678200_B19"},{"key":"2022031303181678200_B20","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1038\/35000219","article-title":"Nogo-A is a myelin-associated neurite outgrowth inhibitor and an antigen for monoclonal antibody IN-1","volume":"403","author":"Chen","year":"2000","journal-title":"Nature"},{"key":"2022031303181678200_B21","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/0896-6273(88)90212-7","article-title":"Antibody against myelin-associated inhibitor of neurite growth neutralizes nonpermissive substrate properties of CNS white matter","volume":"1","author":"Caroni","year":"1988","journal-title":"Neuron"},{"key":"2022031303181678200_B22","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1002\/ana.20420","article-title":"Nogo expression in muscle correlates with amyotrophic lateral sclerosis severity","volume":"57","author":"Jokic","year":"2005","journal-title":"Ann Neurol"},{"key":"2022031303181678200_B23","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1016\/j.conb.2004.01.004","article-title":"Nogo and axon regeneration","volume":"14","author":"Schwab","year":"2004","journal-title":"Curr Opin Neurobiol"},{"key":"2022031303181678200_B24","doi-asserted-by":"crossref","first-page":"12242","DOI":"10.1523\/JNEUROSCI.3827-06.2006","article-title":"The Nogo-Nogo receptor pathway limits a spectrum of adult CNS axonal growth","volume":"26","author":"Cafferty","year":"2006","journal-title":"J Neurosci"},{"key":"2022031303181678200_B25","doi-asserted-by":"crossref","first-page":"5393","DOI":"10.1523\/JNEUROSCI.23-13-05393.2003","article-title":"Nogo-A inhibits neurite outgrowth and cell spreading with three discrete regions","volume":"23","author":"Oertle","year":"2003","journal-title":"J Neurosci"},{"key":"2022031303181678200_B26","doi-asserted-by":"crossref","first-page":"7097","DOI":"10.1523\/JNEUROSCI.22-16-07097.2002","article-title":"Long-lasting sprouting and gene expression changes induced by the monoclonal antibody IN-1 in the adult spinal cord","volume":"22","author":"Bareyre","year":"2002","journal-title":"J Neurosci"},{"key":"2022031303181678200_B27","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/j.expneurol.2004.05.018","article-title":"Neonatal hypoxia suppresses oligodendrocyte Nogo-A and increases axonal sprouting in a rodent model for human prematurity","volume":"189","author":"Weiss","year":"2004","journal-title":"Exp Neurol"},{"key":"2022031303181678200_B28","doi-asserted-by":"crossref","first-page":"10793","DOI":"10.1074\/jbc.M808297200","article-title":"Neuronal Nogo-A modulates growth cone motility via Rho-GTP\/LIMK1\/cofilin in the unlesioned adult nervous system","volume":"284","author":"Montani","year":"2009","journal-title":"J Biol Chem"},{"key":"2022031303181678200_B29","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1002\/jnr.10803","article-title":"Myelin-associated inhibitors of axon regeneration","volume":"74","author":"Grados-Munro","year":"2003","journal-title":"J Neurosci Res"},{"key":"2022031303181678200_B30","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1007\/s11068-007-9014-3","article-title":"Synaptic destabilization by neuronal Nogo-A","volume":"35","author":"Aloy","year":"2006","journal-title":"Brain Cell Biol"},{"key":"2022031303181678200_B31","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1016\/S0304-3940(03)00508-1","article-title":"Electron microscopic localization of Nogo-A at the postsynaptic active zone of the rat","volume":"346","author":"Liu","year":"2003","journal-title":"Neurosci Lett"},{"key":"2022031303181678200_B32","doi-asserted-by":"crossref","first-page":"2753","DOI":"10.1523\/JNEUROSCI.5586-07.2008","article-title":"Synaptic function for the Nogo-66 receptor NgR1: regulation of dendritic spine morphology and activity-dependent synaptic strength","volume":"28","author":"Lee","year":"2008","journal-title":"J Neurosci"},{"key":"2022031303181678200_B33","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1016\/S0896-6273(03)00226-5","article-title":"Systemic deletion of the myelin-associated outgrowth inhibitor Nogo-A improves regenerative and plastic responses after spinal cord injury","volume":"38","author":"Simonen","year":"2003","journal-title":"Neuron"},{"key":"2022031303181678200_B34","doi-asserted-by":"crossref","first-page":"5591","DOI":"10.1523\/JNEUROSCI.1103-06.2006","article-title":"Nogo-A-deficient mice reveal strain-dependent differences in axonal regeneration","volume":"26","author":"Dimou","year":"2006","journal-title":"J Neurosci"},{"key":"2022031303181678200_B35"},{"key":"2022031303181678200_B36"},{"key":"2022031303181678200_B37"},{"key":"2022031303181678200_B38","doi-asserted-by":"crossref","first-page":"S92","DOI":"10.2337\/diabetes.53.suppl_3.S92","article-title":"Beta-cell-targeted expression of a dominant-negative mutant of hepatocyte nuclear factor-1alpha in mice: diabetes model with beta-cell dysfunction partially rescued by nonglucose secretagogues","volume":"53","author":"Winzell","year":"2004","journal-title":"Diabetes"},{"key":"2022031303181678200_B39","doi-asserted-by":"crossref","first-page":"e90","DOI":"10.1097\/00006676-200411000-00162","article-title":"Effects of cholinergic m-receptor agonists on insulin release in islets from obese and lean mice of different ages: the importance of bicarbonate","volume":"29","author":"Persson-Sj\u00f6gren","year":"2004","journal-title":"Pancreas"},{"key":"2022031303181678200_B40","doi-asserted-by":"crossref","first-page":"1324","DOI":"10.2337\/diabetes.54.5.1324","article-title":"Parasympathetic innervation and function of endocrine pancreas requires the glial cell line-derived factor family receptor alpha2 (GFRalpha2)","volume":"54","author":"Rossi","year":"2005","journal-title":"Diabetes"},{"key":"2022031303181678200_B41"},{"key":"2022031303181678200_B42","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1111\/j.1474-8673.1987.tb00143.x","article-title":"The mechanism of 2-deoxy-glucose-induced insulin secretion in the mouse","volume":"7","author":"Karlsson","year":"1987","journal-title":"J Auton Pharmacol"},{"key":"2022031303181678200_B43","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1210\/edrv-10-3-332","article-title":"The contribution of the autonomic nervous system to changes of glucagon and insulin secretion during hypoglycemic stress","volume":"10","author":"Havel","year":"1989","journal-title":"Endocr Rev"},{"key":"2022031303181678200_B44","doi-asserted-by":"crossref","first-page":"781","DOI":"10.1172\/JCI108992","article-title":"Vagal, cholinergic regulation of pancreatic polypeptide secretion","volume":"61","author":"Schwartz","year":"1978","journal-title":"J Clin Invest"},{"key":"2022031303181678200_B45","doi-asserted-by":"crossref","first-page":"18365","DOI":"10.1074\/jbc.M710466200","article-title":"Targeted ablation of glucose-dependent insulinotropic polypeptide-producing cells in transgenic mice reduces obesity and insulin resistance induced by a high fat diet","volume":"283","author":"Althage","year":"2008","journal-title":"J Biol Chem"},{"key":"2022031303181678200_B46"},{"key":"2022031303181678200_B47","doi-asserted-by":"crossref","first-page":"1111","DOI":"10.1038\/sj.ijo.0800523","article-title":"Cholinergic enhancement by pyridostigmine increases the insulin response to glucose load in obese patients but not in normal subjects","volume":"21","author":"Del Rio","year":"1997","journal-title":"Int J Obes Relat Metab Disord"},{"key":"2022031303181678200_B48","doi-asserted-by":"crossref","first-page":"821","DOI":"10.1055\/s-2007-1012448","article-title":"Effects of cholinergic stimulation and antagonism on plasma insulin concentration in lean and obese human subjects","volume":"18","author":"Tappy","year":"1986","journal-title":"Horm Metab Res"},{"key":"2022031303181678200_B49","doi-asserted-by":"crossref","first-page":"1705","DOI":"10.1210\/endo-121-5-1705","article-title":"Evidence that hyperglycemia increases muscarinic binding in pancreatic islets of the rat","volume":"121","author":"Ostenson","year":"1987","journal-title":"Endocrinology"},{"key":"2022031303181678200_B50","first-page":"E93","article-title":"Increased insulin secretion and normalization of glucose tolerance by cholinergic agonism in high fat-fed mice","volume":"277","author":"Ahr\u00e9n","year":"1999","journal-title":"Am J Physiol"},{"key":"2022031303181678200_B51","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1210\/endo.136.2.7835283","article-title":"Enhanced sensitivity of pancreatic islets from preobese 2-week-old ob\/ob mice to neurohormonal stimulation of insulin secretion","volume":"136","author":"Chen","year":"1995","journal-title":"Endocrinology"},{"key":"2022031303181678200_B52","first-page":"R475","article-title":"Muscarinic stimulation maintains in vivo insulin secretion in response to glucose after prolonged hyperglycemia","volume":"268","author":"Balkan","year":"1995","journal-title":"Am J Physiol"},{"key":"2022031303181678200_B53","doi-asserted-by":"crossref","first-page":"2526","DOI":"10.1210\/endo-128-5-2526","article-title":"Differential effects of prolonged hyperglycemia on in vivo and in vitro insulin secretion in rats","volume":"128","author":"Laury","year":"1991","journal-title":"Endocrinology"},{"key":"2022031303181678200_B54","first-page":"E317","article-title":"Hyperinsulinemia of preobese and obese fa\/fa rats is partly vagus nerve mediated","volume":"244","author":"Rohner-Jeanrenaud","year":"1983","journal-title":"Am J Physiol"},{"key":"2022031303181678200_B55","first-page":"565","article-title":"Mechanisms and physiological significance of the cholinergic control of pancreatic beta-cell function","volume":"22","author":"Gilon","year":"2001","journal-title":"Endocr Rev"},{"key":"2022031303181678200_B56"},{"key":"2022031303181678200_B57","doi-asserted-by":"crossref","first-page":"1042","DOI":"10.2337\/diab.38.8.1042","article-title":"Increased beta-cell secretory responsiveness to ceruletide and TPA in streptozocin-induced mildly diabetic rats","volume":"38","author":"Okabayashi","year":"1989","journal-title":"Diabetes"},{"key":"2022031303181678200_B58"},{"key":"2022031303181678200_B59"},{"key":"2022031303181678200_B60"}],"container-title":["Diabetes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.org\/diabetes\/diabetes\/article-pdf\/62\/5\/1443\/573032\/1443.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/diabetesjournals.org\/diabetes\/article-pdf\/62\/5\/1443\/573032\/1443.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,11,2]],"date-time":"2022-11-02T16:32:56Z","timestamp":1667406776000},"score":1,"resource":{"primary":{"URL":"https:\/\/diabetesjournals.org\/diabetes\/article\/62\/5\/1443\/42912\/Nogo-A-Downregulation-Improves-Insulin-Secretion"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,4,16]]},"references-count":60,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2013,4,16]]},"published-print":{"date-parts":[[2013,5,1]]}},"URL":"https:\/\/doi.org\/10.2337\/db12-0949","relation":{},"ISSN":["0012-1797","1939-327X"],"issn-type":[{"value":"0012-1797","type":"print"},{"value":"1939-327X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,4,16]]}}}