title: Decreased first phase insulin response in children with congenital insensitivity to pain with anhidrosis.
abstract: Nerve growth factor (NGF) and its receptor tyrosine kinase A (TrkA) participate in endocrine pancreas morphogenesis and insulin secretion in vitro. Mutations in the TrkA gene cause the syndrome of congenital insensitivity to pain with anhydrosis (CIPA). We hypothesized that CIPA may represent a natural model for impaired NGF effect on insulin secretion in humans. Glucose challenge tests were performed in seven children with CIPA. We calculated the first phase insulin response (FPIR), the second phase insulin response (SPIR) and glucose disposal rate. FPIR was impaired in four and borderline in two patients. SPIR and glucose disposal rate were within the normal range. Oral glucose tolerance test was normal in all patients. Low FPIR in. CIPA suggests for the first time that the NGF-TrkA pathway may play a role in insulin secretion in response to glucose challenge in humans. Additional studies on the clinical significance of NGF-TrkA effects on insulin secretion are required.
authors.affiliation: Pediatric Department, Soroka Medical Center and Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel.
authors.forename: Ruth
authors.initials: R
authors.lastname: Schreiber
authors.forename: Jacov
authors.initials: J
authors.lastname: Levy
authors.forename: Neta
authors.initials: N
authors.lastname: Loewenthal
authors.forename: Vered
authors.initials: V
authors.lastname: Pinsk
authors.forename: Eli
authors.initials: E
authors.lastname: Hershkovitz
mesh_terms: D000293:Adolescent; D001786:Blood Glucose; D002648:Child; D002675:Child, Preschool; D005260:Female; D005951:Glucose Tolerance Test; D009477:Hereditary Sensory and Autonomic Neuropathies / Q000097:blood / Q000235:genetics*; D006801:Humans; D007007:Hypohidrosis / Q000097:blood / Q000235:genetics*; D007328:Insulin / Q000097:blood*; D008297:Male; D000699:Pain Insensitivity, Congenital / Q000097:blood / Q000235:genetics*; D020917:Receptor, trkA / Q000235:genetics*
chemical_list: D001786:Blood Glucose; D007328:Insulin; D020917:Receptor, trkA