12 research outputs found
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Use of metformin to control clozapine-associated weight gain in an adolescent with schizoaffective disorder
Novel Presentations of Congenital Hyperinsulinism due to Mutations in the MODY genes: HNF1A
High Risk of Diabetes and Neurobehavioral Deficits in Individuals With Surgically Treated Hyperinsulinism
Identification of transcriptional targets during pancreatic growth after partial pancreatectomy and exendin-4 treatment
Postoperative Surveillance and Detection of Postprandial Hypoglycemia after Fundoplasty in Children
A liquid chromatography-mass spectrometry assay for quantification of Exendin[9-39] in human plasma
Prevalence of Adverse Events in Children With Congenital Hyperinsulinism Treated With Diazoxide
Functional and Metabolomic Consequences of KATP Channel Inactivation in Human Islets
Loss-of-function mutations of 尾-cell KATP channels cause the most severe form of congenital hyperinsulinism (KATPHI). KATPHI is characterized by fasting and protein-induced hypoglycemia that is unresponsive to medical therapy. For a better understanding of the pathophysiology of KATPHI, we examined cytosolic calcium ([Ca2+]i), insulin secretion, oxygen consumption, and [U-13C]glucose metabolism in islets isolated from the pancreases of children with KATPHI who required pancreatectomy. Basal [Ca2+]i and insulin secretion were higher in KATPHI islets compared with controls. Unlike controls, insulin secretion in KATPHI islets increased in response to amino acids but not to glucose. KATPHI islets have an increased basal rate of oxygen consumption and mitochondrial mass. [U-13C]glucose metabolism showed a twofold increase in alanine levels and sixfold increase in 13C enrichment of alanine in KATPHI islets, suggesting increased rates of glycolysis. KATPHI islets also exhibited increased serine/glycine and glutamine biosynthesis. In contrast, KATPHI islets had low 纬-aminobutyric acid (GABA) levels and lacked 13C incorporation into GABA in response to glucose stimulation. The expression of key genes involved in these metabolic pathways was significantly different in KATPHI 尾-cells compared with control, providing a mechanism for the observed changes. These findings demonstrate that the pathophysiology of KATPHI is complex, and they provide a framework for the identification of new potential therapeutic targets for this devastating condition.</jats:p