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Citations to this article

Defective insulin secretion in hepatocyte nuclear factor 1alpha-deficient mice.
M Pontoglio, … , M Yaniv, K S Polonsky
M Pontoglio, … , M Yaniv, K S Polonsky
Published May 15, 1998
Citation Information: J Clin Invest. 1998;101(10):2215-2222. https://doi.org/10.1172/JCI2548.
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Defective insulin secretion in hepatocyte nuclear factor 1alpha-deficient mice.

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Abstract

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.

Authors

M Pontoglio, S Sreenan, M Roe, W Pugh, D Ostrega, A Doyen, A J Pick, A Baldwin, G Velho, P Froguel, M Levisetti, S Bonner-Weir, G I Bell, M Yaniv, K S Polonsky

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Year: 2025 2024 2023 2022 2021 2020 2019 2018 2017 2016 2015 2014 2013 2012 2011 2010 2009 2008 2007 2006 2005 2004 2003 2002 2001 2000 1999 1998 1994 1990 Total
Citations: 2 1 3 11 8 8 6 3 7 10 11 4 4 9 10 14 13 11 7 9 13 12 16 13 20 12 10 3 1 1 252
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Citations to this article in year 2005 (13)

Title and authors Publication Year
The MODY gene HNF-4 alpha regulates selected genes involved in insulin secretion
Rana K. Gupta, Marko Z. Vatamaniuk, Catherine S. Lee, Reed C. Flaschen, James T. Fulmer, Franz M. Matschinsky, Stephen A. Duncan, Klaus H. Kaestner
Journal of Clinical Investigation 2005
Minireview: Transcriptional Regulation in Pancreatic Development
JF Habener, DM Kemp, MK Thomas
Endocrinology 2005
The MODY1 gene HNF-4α regulates selected genes involved in insulin secretion
RK Gupta, MZ Vatamaniuk, CS Lee, RC Flaschen, JT Fulmer, FM Matschinsky, SA Duncan, KH Kaestner
Journal of Clinical Investigation 2005
The HNF-1 target Collectrin controls insulin exocytosis by SNARE complex formation
K Fukui, Q Yang, Y Cao, N Takahashi, H Hatakeyama, H Wang, J Wada, Y Zhang, L Marselli, T Nammo, K Yoneda, M Onishi, S Higashiyama, Y Matsuzawa, FJ Gonzalez, GC Weir, H Kasai, I Shimomura, J Miyagawa, CB Wollheim, K Yamagata
Cell Metabolism 2005
Genetics of type 2 diabetes mellitus: status and perspectives
L Hansen, O Pedersen
Diabetes, Obesity and Metabolism 2005
Collecting new targets in MODY
KH Kaestner
Cell Metabolism 2005
Optical imaging of pancreatic beta cells in living mice expressing a mouse insulin I promoter-firefly luciferase transgene
SY Park, X Wang, Z Chen, AC Powers, MA Magnuson, WS Head, DW Piston, GI Bell
genesis 2005
Diagnosis and Management of Maturity-Onset Diabetes of the Young
J Timsit, C Bellann??-Chantelot, D Dubois-Laforgue, G Velho
Treatments in Endocrinology 2005
Genetic and clinical characteristics of maturity-onset diabetes of the young
FM Giuffrida, AF Reis
Diabetes, Obesity and Metabolism 2005
Preserved insulin response to tolbutamide in hepatocyte nuclear factor-1α mutation carriers
JV Sagen, ER Pearson, A Johansen, G Spyer, O Søvik, O Pedersen, PR Njølstad, AT Hattersley, T Hansen
Diabetic Medicine 2005
The mouse RNase 4 and RNase 5/ang 1 locus utilizes dual promoters for tissue-specific expression
KD Dyer, HF Rosenberg
Nucleic Acids Research 2005
Genes and Type 2 Diabetes Mellitus
MT Luna
Archives of Medical Research 2005
Diagnosis and Management of Maturity-Onset Diabetes of the Young:
J Timsit, C Bellann??-Chantelot, D Dubois-Laforgue, G Velho
Treatments in Endocrinology 2005

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