The DOI matches its Crossref record; 25 of the 25 references it cites were found in a registry or an index.
Defective insulin secretion in hepatocyte nuclear factor 1alpha-deficient mice.
Open accessAbstract
Mutations in the gene for the transcription factor hepatocyte nuclear factor (HNF) 1alpha cause maturity-onset diabetes of the young (MODY) 3, a form of diabetes that results from defects in insulin secretion. Since the nature of these defects has not been defined, we compared insulin secretory function in heterozygous [HNF-1alpha (+/-)] or homozygous [HNF-1alpha (-/-)] mice with null mutations in the HNF-1alpha gene with their wild-type littermates [HNF-1alpha (+/+)]. Blood glucose concentrations were similar in HNF-1alpha (+/+) and (+/-) mice (7.8+/-0.2 and 7.9+/-0.3 mM), but were significantly higher in the HNF-1alpha (-/-) mice (13.1+/-0.7 mM, P < 0.001). Insulin secretory responses to glucose and arginine in the perfused pancreas and perifused islets from HNF-1alpha (-/-) mice were < 15% of the values in the other two groups and were associated with similar reductions in intracellular Ca2+ responses. These defects were not due to a decrease in glucokinase or insulin gene transcription. beta cell mass adjusted for body weight was not reduced in the (-/-) animals, although pancreatic insulin content adjusted for pancreas weight was slightly lower (0.06+/-0.01 vs. 0.10+/-0.01 microg/mg, P < 0.01) than in the (+/+) animals. In summary, a null mutation in the HNF-1alpha gene in homozygous mice leads to diabetes due to alterations in the pathways that regulate beta cell responses to secretagogues including glucose and arginine. These results provide further evidence in support of a key role for HNF-1alpha in the maintenance of normal beta cell function.
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“it is the loss of HNF1α resulting in an almost abolished insulin secretion, likely due to a decreased response to intracellular calcium.”
From Pancreatic regulation of glucose homeostasis. (2016) · cites this paper as [176]
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“These findings support the importance of HNF1α in maintaining β-cell function176 and its involvement in maturity-onset diabetes of the young (MODY3).177”
From Pancreatic regulation of glucose homeostasis. (2016) · cites this paper as [176]
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Self-citationInteraction of a Liver-Specific Nuclear Factor with the Fibrinogen and α 1 -Antitrypsin Promoters
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Items 301–320 of 320
M OLECULAR M ECHANISMS AND C LINICAL P ATHOPHYSIOLOGY OF M ATURITY -O NSET D IABETES OF THE Y OUNG
Ajans, S. T. S. F., Ell, G. R. I. B., Enneth, A. K., & Olonsky, S. P. (2001)
Nonalcoholic Fatty Liver Disease and Diabetes Mellitus
Adams, L. A. (2007) · CRC Press eBooks · doi:10.3109/9780849379581-38
Knebel, B. (2007) · CRC Press eBooks · doi:10.3109/9780849379581-36
Energy Homeostasis During Fasting and Fed States: Foxa2 Regulates Hepatic Amino Acid Uptake
Lee, V. M. (2007) · Digital Commons - RU (Rockefeller University) · doi:10.48496/em89-nh27
Caetano, L. A. (2018) · Digital Library of Theses and Dissertations (Universidade de São Paulo) · doi:10.11606/t.5.2018.tde-26032018-131334
Pediatric Diabetes: Review Article
Bavishna, B., Devi, R. U., & Krishnan, S. G. (2019) · Indian Journal of Public Health Research & Development · doi:10.5958/0976-5506.2019.04013.0
Dissecting Pancreatic β-cell Stress Using Whole Transcriptome Sequencing
Stancill, J. S. (2017)
Development of the Endocrine Pancreas
Hebrok, M., & German, M. S. (2010) · Elsevier eBooks · doi:10.1016/b978-1-4160-5583-9.00031-9
Tiermodelle in der biomedizinischen Forschung
Strehle, M., & Britisch, S. (2008) · Springer eBooks · doi:10.1007/978-3-540-69414-4_9
HNF1α transcriptional activation and repression maintain human islet α and β cell functionPreprint
Qian, M. F., Bevacqua, R. J., Nguyen, V., Liu, X., Zhao, W., Chang, C., Gu, X., Dai, X.-Q., MacDonald, P. E., & Kim, S. K. (2022) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2022.09.25.509394
“In humans, HNF1A haploinsufficiency underlies HNF1A-MODY, but mice heterozygous for an Hnf1a null allele are not diabetic (Pontoglio et al. 1998).”
BackgroundFirdous, P., Nissar, K., Masoodi, S. R., Wani, J. A., Hassan, T., & Ganai, B. A. (2022) · Journal of Endocrinological Investigation · doi:10.1007/s40618-022-01953-w
“The reduction in GSIS and hyperglycemia in homozygous knockout mice has been attributed to the defective glycolytic signaling proximal to mitochondrial oxidation [7, 23, 24] and possibly in response to the defective mitochondrial functioning [30].”
BackgroundSharmine, S., Unger, L., Altankhuyag, A., Legøy, T. A., Ghila, L., & Chera, S. (2025) · Research Square · doi:10.21203/rs.3.rs-8013440/v1
Acosta-Montalvo, A. (2022) · theses.fr (ABES) · doi:10.70675/3712a689zf56fz4ce7z814bz28dc25f0cc70
Mapping the genetic landscape of HNF1B-dependent cell growth
Gaglioti, D. (2024) · theses.fr (ABES) · doi:10.70675/0d561dcezfd54z4e38z89fezef3bd730482b
Lorenzo, D. (2024) · theses.fr (ABES) · doi:10.70675/ba1107b2ze1c9z4e6ezad24z3a1778a18d7e
Progressive HNF1A-MODY pathophysiology revealed by a translational mouse model
Louvet, I., Acosta-Montalvo, A., Saponaro, C., Moreno-Lopez, M., Douffi, S., Karchaoui, A. E., Pasquetti, G., Thévenet, J., Delalleau, N., Gmyr, V., et al. (2026) · JCI Insight · doi:10.1172/jci.insight.198095
“…human HNF1A-MODY has enabled us to identify previously unrecognized pathogenic mechanisms with substantial implications for disease monitoring and biomarker development, offering a marked advantage over previous knockout models that display immediate, non-progressive severity (16, 17, 19, 46, 53).”
Pancreatic Development in the Context of Diabetes
Hewitt, L., & Grapin‐Botton, A. (2026) · Elsevier eBooks · doi:10.1016/b978-0-443-11985-9.00001-9
Metadata
- Authors
- Pontoglio, M., Sreenan, S., Roe, M., Pugh, W., Ostrega, D., Doyen, A., Pick, A. J., Baldwin, A., Velho, G., Froguel, P., Levisetti, M., Bonner-Weir, S., Bell, G. I., Yaniv, M., & Polonsky, K. S.
- Affiliations
- Centre National de la Recherche Scientifique (FR)
- Institut Pasteur de Lille (FR)
- Inserm (FR)
- Howard Hughes Medical Institute (US)
- Venue
- Journal of Clinical Investigation
- Published
- 1998-05-15
- Volume
- 101
- Issue
- 10
- Pages
- 2215-2222
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC508809
- OpenAlex
- W2095311108
- Cited by
- 321
- References
- 23
- Citations by year
- 2026: 4 · 2025: 8 · 2024: 4 · 2023: 3 · 2022: 14 · 2021: 11 · 2020: 7 · 2019: 7 · 2018: 5 · 2017: 8 · 2016: 7 · 2015: 16 · 2014: 7 · 2013: 4 · 2012: 11
- FWCI
- 21.87
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5p01dk044840-10)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK 44840, DK-31842, DK 20595)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pancreatic function and diabetes
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Keywords
- HNF1A, maturity-onset diabetes of the young, MODY3, insulin secretion, beta-cell function, glucose-stimulated insulin secretion, arginine-stimulated insulin secretion, intracellular calcium, hyperglycemia, insulin content, glucokinase, insulin gene transcription
- MeSH terms
- Insulin Secretion, Animals, Arginine, Blood Glucose, Body Weight, Calcium, Diabetes Mellitus, Type 2, DNA-Binding Proteins, Gene Expression Regulation, Glucose, Heterozygote, Homozygote, Immunohistochemistry, Insulin, Islets of Langerhans, Nuclear Proteins, Organ Size, Pancreas, RNA, Messenger, Transcription Factors, Mice, Knockout, Mice, Hepatocyte Nuclear Factor 1, Hepatocyte Nuclear Factor 1-alpha, Hepatocyte Nuclear Factor 1-beta
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