ArticleThe Journal of clinical investigation2011
In vitro insulin secretion by pancreatic tissue from infants with diazoxide-resistant congenital hyperinsulinism deviates from model predictions.
Article in The Journal of clinical investigation, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 1 of them a synthesis that pooled it.
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Who cites it
26 citing papers in PubMed, 1 synthesis or guideline pooled it, 51 citations in OpenAlex.
- Efficacy and safety of diazoxide for treating hyperinsulinemic hypoglycemia: A systematic review and meta-analysis.PloS one · 2021Pooled it
- Ghrelin and relamorelin counteract hypoglycemia in mice engrafted with congenital hyperinsulinism stem cell-derived islets.Stem cells translational medicine · 2026Article
- Loss of β-Cell KATP Reduces Ca2+ Sensitivity of Insulin Secretion and Trpm5 Expression.Diabetes · 2025Article
- Standardised practices in the networked management of congenital hyperinsulinism: a UK national collaborative consensus.Frontiers in endocrinology · 2023Review
- Investigation of the Therapeutic Potential of New Antidiabetic Compounds Using Islet-on-a-Chip Microfluidic Model.Biosensors · 2022Article
- ATP-Sensitive Potassium Channels in Hyperinsulinism and Type 2 Diabetes: Inconvenient Paradox or New Paradigm?Diabetes · 2022Review
- Stem Cell Based Models in Congenital Hyperinsulinism - Perspective on Practicalities and Possibilities.Frontiers in endocrinology · 2022Review
- SUR1-mutant iPS cell-derived islets recapitulate the pathophysiology of congenital hyperinsulinism.Diabetologia · 2021Article
- Hyperinsulinemic hypoglycemia in children and adolescents: Recent advances in understanding of pathophysiology and management.Reviews in endocrine & metabolic disorders · 2020Review
- Therapies and outcomes of congenital hyperinsulinism-induced hypoglycaemia.Diabetic medicine : a journal of the British Diabetic Association · 2019Review
- Functional and Metabolomic Consequences of KDiabetes · 2017Article
- Congenital Hyperinsulinism Caused by aEJIFCC · 2017Article
- Benign Tumors and Tumorlike Lesions of the Pancreas.Surgical pathology clinics · 2016Review
- Hyperinsulinemic Hypoglycemia - The Molecular Mechanisms.Frontiers in endocrinology · 2016Review
- Dynamics and Regulation of Insulin Secretion in Pancreatic Islets from Normal Young Children.PloS one · 2016Article
- Dipeptidyl peptidase-4 expression in pancreatic tissue from patients with congenital hyperinsulinism.International journal of clinical and experimental pathology · 2015Article
- Mapping of long-range INS promoter interactions reveals a role for calcium-activated chloride channel ANO1 in insulin secretion.Proceedings of the National Academy of Sciences of the United States of America · 2014Article
- Uncoupling of secretion from growth in some hormone secretory tissues.The Journal of clinical endocrinology and metabolism · 2014Review
- Reduced Glycemic Variability in Diazoxide-Responsive Children with Congenital Hyperinsulinism Using Supplemental Omega-3-Polyunsaturated Fatty Acids; A Pilot Trial with MaxEPA(R.).Frontiers in endocrinology · 2014Article
- Roles of lncRNAs in pancreatic beta cell identity and diabetes susceptibility.Frontiers in genetics · 2014Review
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Authors and funding
9 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Congenital hyperinsulinism (CHI) is the major cause of persistent neonatal hypoglycemia. CHI most often occurs due to mutations in the ABCC8 (which encodes sulfonylurea receptor 1) or KCNJ11 (which encodes the potassium channel Kir6.2) gene, which result in a lack of functional KATP channels in pancreatic β cells. Diffuse forms of CHI (DiCHI), in which all β cells are abnormal, often require subtotal pancreatectomy, whereas focal forms (FoCHI), which are characterized by localized hyperplasia of abnormal β cells, can be cured by resection of the lesion. Here, we characterized the in vitro kinetics of insulin secretion by pancreatic fragments from 6 DiCHI patients and by focal lesion and normal adjacent pancreas from 18 FoCHI patients. Responses of normal pancreas were similar to those reported for islets from adult organ donors. Compared with normal pancreas, basal insulin secretion was elevated in both FoCHI and DiCHI tissue. Affected tissues were heterogeneous in their secretory responses, with increased glucose levels often producing a rapid increase in insulin secretion that could be followed by a paradoxical decrease below prestimulatory levels. The KATP channel blocker tolbutamide was consistently ineffective in stimulating insulin secretion; conversely, the KATP channel activator diazoxide often caused an unanticipated increase in insulin secretion. These observed alterations in secretory behavior were similar in focal lesion and DiCHI tissue, and independent of the specific mutation in ABCC8 or KCNJ11. They cannot be explained by classic models of β cell function. Our results provide insight into the excessive and sometimes paradoxical changes in insulin secretion observed in CHI patients with inactivating mutations of KATP channels.
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