ArticleThe Journal of clinical investigation2001
Development of diabetes mellitus in aging transgenic mice following suppression of pancreatic homeoprotein IDX-1.
Article in The Journal of clinical investigation, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 74 citations in OpenAlex.
- Mutant Huntingtin Impairs Pancreatic β-cells by Recruiting IRS-2 and Disturbing the PI3K/AKT/FoxO1 Signaling Pathway in Huntington's Disease.Journal of molecular neuroscience : MN · 2021Article
- Biallelic PDX1 (insulin promoter factor 1) mutations causing neonatal diabetes without exocrine pancreatic insufficiency.Diabetic medicine : a journal of the British Diabetic Association · 2013Article
- Conditional gene expression systems in the transgenic rat brain.BMC biology · 2012Article
- Metabolic syndrome in mice induced by expressing a transcriptional activator in adipose tissue.Transgenic research · 2012Article
- Maintenance of β-cell maturity and plasticity in the adult pancreas: developmental biology concepts in adult physiology.Diabetes · 2012Review
- Review
- β-Cell Specific Overexpression of GPR39 Protects against Streptozotocin-Induced Hyperglycemia.International journal of endocrinology · 2011Article
- Modeling multiple sclerosis in laboratory animals.Seminars in immunopathology · 2009Review
- The relationship of serum AGE levels in diabetic mothers with adverse fetal outcome.Journal of perinatology : official journal of the California Perinatal Association · 2009Article
- A new mouse model for temporal- and tissue-specific control of extracellular superoxide dismutase.Genesis (New York, N.Y. : 2000) · 2009Article
- PDX-1 interaction and regulation of the Pancreatic Derived Factor (PANDER, FAM3B) promoter.Biochimica et biophysica acta · 2008Article
- Transcriptional regulation of the distal promoter of the rat pyruvate carboxylase gene by hepatocyte nuclear factor 3beta/Foxa2 and upstream stimulatory factors in insulinoma cells.The Biochemical journal · 2007Article
- Regulation of insulin secretion and beta-cell mass by activating signal cointegrator 2.Molecular and cellular biology · 2006Article
- Suppression of Pdx-1 perturbs proinsulin processing, insulin secretion and GLP-1 signalling in INS-1 cells.Diabetologia · 2005Article
- Identification of PCIF1, a POZ domain protein that inhibits PDX-1 (MODY4) transcriptional activity.Molecular and cellular biology · 2004Article
- Transcriptional networks controlling pancreatic development and beta cell function.Diabetologia · 2004Review
- Increased islet apoptosis in Pdx1+/- mice.The Journal of clinical investigation · 2003Article
- Lessons for human diabetes from experimental mouse models.Current diabetes reports · 2003Review
- Pituitary tumor transforming gene-null male mice exhibit impaired pancreatic beta cell proliferation and diabetes.Proceedings of the National Academy of Sciences of the United States of America · 2003Article
- Developmental aspects of the endocrine pancreas.Reviews in endocrine & metabolic disorders · 2003Review
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 1 country.
Funding
Abstract
Monogenic forms of diabetes can result from mutations in genes encoding transcription factors. Mutations in the homeodomain transcription factor IDX-1, a critical regulator of pancreas development and insulin gene transcription, confer a strong predisposition to the development of diabetes mellitus in humans. To investigate the role of IDX-1 expression in the pathogenesis of diabetes, we developed a model for the inducible impairment of IDX-1 expression in pancreatic beta cells in vivo by engineering an antisense ribozyme specific for mouse IDX-1 mRNA under control of the reverse tetracycline transactivator (rtTA). Doxycycline-induced impairment of IDX-1 expression reduced activation of the Insulin promoter but activated the Idx-1 promoter, suggesting that pancreatic beta cells regulate IDX-1 transcription to maintain IDX-1 levels within a narrow range. In transgenic mice that express both rtTA and the antisense ribozyme construct, impaired IDX-1 expression elevated glycated hemoglobin levels, diminished glucose tolerance, and decreased insulin/glucose ratios. Metabolic phenotypes induced by IDX-1 deficiency were observed predominantly in male mice over 18 months of age, suggesting that cellular mechanisms to protect IDX-1 levels in pancreatic beta cells decline with aging. We propose that even in the absence of Idx-1 gene mutations, pathophysiological processes that decrease IDX-1 levels are likely to impair glucose tolerance. Therapeutic strategies to attain normal glucose homeostasis by restoring normal IDX-1 levels may be of particular importance for older individuals with diabetes mellitus.
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