title: Fine tuning of insulin secretion by release of nerve growth factor from mouse and human islet β-cells.
abstract: Nerve growth factor (NGF) is a protein required for neuronal development that also has regulatory functions in non-neuronal cells. Both NGF and its membrane receptors trkA and p75(NTR) are expressed by islet β-cells. In this study we dynamically profiled NGF secretion from islets and used selective trkA and p75(NTR) inhibitors to identify the role of endogenous NGF in β-cell stimulus-secretion coupling. NGF secretion from mouse islets was transient and did not accompany the sustained second phase of glucose-induced insulin secretion. Despite being present in human islets, NGF was not released at sufficient levels to be quantified. Inhibition of NGF signaling through trkA and p75(NTR) increased basal insulin secretion from both human and mouse islets, but impaired glucose-stimulated insulin secretion. These data support a role for islet NGF in fine-tuning insulin secretion, to both maintain a low basal level of insulin output and contribute to the biphasic secretory response to glucose.
authors.affiliation: Diabetes Research Group, Diabetes & Nutritional Sciences Division, King's College London, Guy's Campus, SE1 1UL, London, United Kingdom.
authors.forename: Attilio
authors.initials: A
authors.lastname: Pingitore
authors.affiliation: Department of Pharmacy, Nutritional and Health Sciences, University of Calabria, Via Savinio, 87036, Rende, Italy.
authors.forename: Maria Cristina
authors.initials: MC
authors.lastname: Caroleo
authors.affiliation: Department of Pharmacy, Nutritional and Health Sciences, University of Calabria, Via Savinio, 87036, Rende, Italy.
authors.forename: Erika
authors.initials: E
authors.lastname: Cione
authors.affiliation: Department of General Surgery, Rio Carrión Hospital, University Hospital Complex of Palencia, 34005, Palencia, Spain.
authors.forename: Ramon
authors.initials: R
authors.lastname: Castañera Gonzalez
authors.affiliation: Diabetes Research Group, Diabetes & Nutritional Sciences Division, King's College London, Guy's Campus, SE1 1UL, London, United Kingdom.
authors.forename: Guo Cai
authors.initials: GC
authors.lastname: Huang
authors.affiliation: Diabetes Research Group, Diabetes & Nutritional Sciences Division, King's College London, Guy's Campus, SE1 1UL, London, United Kingdom. Electronic address: shanta.persaud@kcl.ac.uk.
authors.forename: Shanta J
authors.initials: SJ
authors.lastname: Persaud
mesh_terms: D000818:Animals; D005260:Female; D005947:Glucose / Q000494:pharmacology; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008813:Mice, Inbred ICR; D008875:Middle Aged; D020932:Nerve Growth Factor / Q000378:metabolism*; D011485:Protein Binding / Q000187:drug effects; D020917:Receptor, trkA / Q000378:metabolism; D017475:Receptors, Nerve Growth Factor / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D062947:rho-Specific Guanine Nucleotide Dissociation Inhibitors / Q000378:metabolism
chemical_list: D007328:Insulin; D017475:Receptors, Nerve Growth Factor; C517634:Ngfr protein, mouse; D062947:rho-Specific Guanine Nucleotide Dissociation Inhibitors; D020932:Nerve Growth Factor; D020917:Receptor, trkA; D005947:Glucose
keywords: Insulin secretion; Islets of Langerhans; NGF; p75(NTR); trkA; β-cells