ArticleProceedings of the National Academy of Sciences of the United States of America2011
Modulation of pancreatic islets-stress axis by hypothalamic releasing hormones and 11beta-hydroxysteroid dehydrogenase.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 2 of them syntheses that pooled it.
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Who cites it
29 citing papers in PubMed, 2 syntheses or guidelines pooled it, 54 citations in OpenAlex.
- Effects of diabetes-related family stress on glycemic control in young patients with type 1 diabetes: Systematic review.Canadian family physician Medecin de famille canadien · 2013Pooled it
- Large-scale association analyses identify new loci influencing glycemic traits and provide insight into the underlying biological pathways.Nature genetics · 2012Pooled it
- Identification of novel genomic variants in diabetic nephropathy patients using whole-exome sequencing: a pilot investigation.Frontiers in endocrinology · 2026Article
- Genetic Crosstalk Between Type 1 Diabetes and Sjögren's Syndrome: A Systematic Exploration of Risk Genes and Common Pathways.Journal of cellular and molecular medicine · 2025Article
- GHRH in diabetes and metabolism.Reviews in endocrine & metabolic disorders · 2025Review
- Growth hormone-releasing hormone and its analogues in health and disease.Nature reviews. Endocrinology · 2025Review
- Novel corticotropin-releasing hormone receptor genes (CRHR1 and CRHR2) linkage to and association with polycystic ovary syndrome.Journal of ovarian research · 2023Article
- Article
- Risks of Developing Diabetes and Hyperglycemic Crisis Following Carbon Monoxide Poisoning: A Study Incorporating Epidemiologic Analysis and Animal Experiment.Clinical epidemiology · 2022Article
- Beta-Cell Adaptation to Pregnancy - Role of Calcium Dynamics.Frontiers in endocrinology · 2022Review
- Steroids, steroid associated substances and gestational diabetes mellitus.Physiological research · 2021Review
- Article
- SurfaceGenie: a web-based application for prioritizing cell-type-specific marker candidates.Bioinformatics (Oxford, England) · 2020Article
- UCN2: a new candidate influencing pancreatic β-cell adaptations in pregnancy.The Journal of endocrinology · 2020Article
- Maternal β-Cell Adaptations in Pregnancy and Placental Signalling: Implications for Gestational Diabetes.International journal of molecular sciences · 2018Review
- Approaches and advances in the genetic causes of autoimmune disease and their implications.Nature immunology · 2018Review
- Analysis of Purified Pancreatic Islet Beta and Alpha Cell Transcriptomes Reveals 11β-Hydroxysteroid Dehydrogenase (Hsd11b1) as a Novel Disallowed Gene.Frontiers in genetics · 2017Article
- Survival of encapsulated islets: More than a membrane story.World journal of transplantation · 2016Review
- Growth Hormone-Releasing Hormone in Diabetes.Frontiers in endocrinology · 2016Review
- 11β-HSD1 modulates LPS-induced innate immune responses in adipocytes by altering expression of PTEN.Molecular endocrinology (Baltimore, Md.) · 2015Article
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Authors and funding
13 authors at 6 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Corticotropin-releasing hormone (CRH) and growth hormone-releasing hormone (GHRH), primarily characterized as neuroregulators of the hypothalamic-pituitary-adrenal axis, directly influence tissue-specific receptor-systems for CRH and GHRH in the endocrine pancreas. Here, we demonstrate the expression of mRNA for CRH and CRH-receptor type 1 (CRHR1) and of protein for CRHR1 in rat and human pancreatic islets and rat insulinoma cells. Activation of CRHR1 and GHRH-receptor significantly increased cell proliferation and reduced cell apoptosis. CRH stimulated both cellular content and release of insulin in rat islet and insulinoma cells. At the ultrastructural level, CRHR1 stimulation revealed a more active metabolic state with enlarged mitochondria. Moreover, glucocorticoids that promote glucose production are balanced by both 11b-hydroxysteroid dehydrogenase (11β-HSD) isoforms; 11β-HSD-type-1 and 11β-HSD-type-2. We demonstrated expression of mRNA for 11β-HSD-1 and 11β-HSD-2 and protein for 11β-HSD-1 in rat and human pancreatic islets and insulinoma cells. Quantitative real-time PCR revealed that stimulation of CRHR1 and GHRH-receptor affects the metabolism of insulinoma cells by down-regulating 11β-HSD-1 and up-regulating 11β-HSD-2. The 11β-HSD enzyme activity was analyzed by measuring the production of cortisol from cortisone. Similarly, activation of CRHR1 resulted in reduced cortisol levels, indicating either decreased 11β-HSD-1 enzyme activity or increased 11β-HSD-2 enzyme activity; thus, activation of CRHR1 alters the glucocorticoid balance toward the inactive form. These data indicate that functional receptor systems for hypothalamic-releasing hormone agonists exist within the endocrine pancreas and influence synthesis of insulin and the pancreatic glucocorticoid shuttle. Agonists of CRHR1 and GHRH-receptor, therefore, may play an important role as novel therapeutic tools in the treatment of diabetes mellitus.
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