ArticleInternational journal of clinical and experimental pathology2010
Persistent hyperinsulinemic hypoglycemia of infancy: constitutive activation of the mTOR pathway with associated exocrine-islet transdifferentiation and therapeutic implications.
Article in International journal of clinical and experimental pathology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 31 citations in OpenAlex.
- Sirolimus in infants with congenital hyperinsulinism (CHI) - a single-centre experience.European journal of pediatrics · 2022Article
- Congenital hyperinsulinism in clinical practice: From biochemical pathophysiology to new monitoring techniques.Frontiers in pediatrics · 2022Review
- Sirolimus Therapy and Follow-up in a Patient with Severe Congenital Hyperinsulinism Following Subtotal PancreatectomyJournal of clinical research in pediatric endocrinology · 2021Article
- Hyperinsulinemic hypoglycemia in children and adolescents: Recent advances in understanding of pathophysiology and management.Reviews in endocrine & metabolic disorders · 2020Review
- Sirolimus: Efficacy and Complications in Children With Hyperinsulinemic Hypoglycemia: A 5-Year Follow-Up Study.Journal of the Endocrine Society · 2019Article
- Article
- Congenital Hyperinsulinism: Diagnosis and Treatment Update.Journal of clinical research in pediatric endocrinology · 2017Review
- Morphoproteomics and biomedical analytics coincide with clinical outcomes in supporting a constant but variable role for the mTOR pathway in the biology of congenital hyperinsulinism of infancy.Orphanet journal of rare diseases · 2017Article
- Approach to hypoglycemia in infants and children.Translational pediatrics · 2017Review
- Distinct roles for the mTOR pathway in postnatal morphogenesis, maturation and function of pancreatic islets.Development (Cambridge, England) · 2017Article
- Extreme caution on the use of sirolimus for the congenital hyperinsulinism in infancy patient.Orphanet journal of rare diseases · 2017Article
- Congenital Hypoglycemia Disorders: New Aspects of Etiology, Diagnosis, Treatment and Outcomes: Highlights of the Proceedings of the Congenital Hypoglycemia Disorders Symposium, Philadelphia April 2016.Pediatric diabetes · 2017Article
- Diagnosis and treatment of hyperinsulinaemic hypoglycaemia and its implications for paediatric endocrinology.International journal of pediatric endocrinology · 2017Review
- Sirolimus therapy in a child with partially diazoxide-responsive hyperinsulinaemic hypoglycaemia.Endocrinology, diabetes & metabolism case reports · 2016Article
- The Diagnosis and Management of Hyperinsulinaemic Hypoglycaemia.Journal of clinical research in pediatric endocrinology · 2015Review
- Dipeptidyl peptidase-4 expression in pancreatic tissue from patients with congenital hyperinsulinism.International journal of clinical and experimental pathology · 2015Article
- Non-small cell lung carcinoma therapy using mTOR-siRNA.International journal of clinical and experimental pathology · 2012Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundAmino-acids stimulate the mammalian target of rapamycin complex(mTORC)1; mTORC1 integrates amino-acid and energy-sensing pathways in beta-cells. Rapamycin inhibits mTORC1. We examined the mTOR pathway and cell cycle data in the exocrine pancreas in diffuse persistent hyperinsulinemic hypoglycemia of infancy (PHHI).
designTissues from two diffuse PHHI cases, one pediatric control and from adult pancreatic tissue microarray were analyzed. The case studies are newborns of non-diabetic mothers, one with SUR1 mutation, and the other with a family history of PHHI. Immunostaining for (p)-mTOR(Ser2448), phospholipase(PLD)1, cell cycle analytes ( Ki67, Skp2, p27Kip1), and insulin were performed. Cell cycle analytes were assessed by automated cellular imaging or visual quantification. Multispectral imaging of double immunostaining for insulin/p-mTOR and transmission electron microscopy (TEM) were performed.
resultsHematoxylin-eosin and insulin-staining showed beta-cell hyperplasia in the exocrine pancreas, without mass effect. Overexpression of (p)-mTOR on the plasmalemmal, but not nuclear compartment, consistent with mTORC1, was noted in acinar elements. Residual expression was noted in islets. Double immunostaining revealed occasional exocrine cells co-expressing mTOR and insulin. No such co-expressions were seen in the control. TEM showed acinar cells containing zymogen and hormone-secreting granules. No nuclear Skp2 was noted. Obversely, p27Kip1 was expressed. Mitotic index was 1/40 (0.25/10) HPF.
conclusionMorphoproteomic, histopathologic and morphometric findings in this study of diffuse PHHI coincide with existing genomic and signal transduction data in: 1) supporting a role for a constitutively activated and overexpressed mTORC1 pathway in the acinar pancreas in its pathogenesis; 2) reaffirming transdifferentiation of acinar-to-islet cells; 3) raising the possibility of rapamycin as a therapeutic option in PHHI.
Indexed as
Identifiers
20830240PMC2933389W1718583305What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.