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.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Loss of HNF1α results in almost abolished insulin secretion, likely due to a decreased response to intracellular calcium.
“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]
The Discussion reports an 87% reduction in insulin secretion in homozygous HNF-1α-deficient mice, supporting the description of an almost abolished response. The section on changes in islet intracellular Ca²⁺ reports a reduced calcium response to glucose, not a decreased insulin-secretory response to intracellular calcium; it does not establish the proposed mechanism as phrased. (LLM, conf=0.85)
Experimental — accuracy not yet measuredHNF1α is important in maintaining β-cell function and is involved in maturity-onset diabetes of the young (MODY3).
“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]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Mutations in the hepatocyte nuclear factor-1α gene in maturity-onset diabetes of the young (MODY3)
Yamagata, K., Oda, N., Kaisaki, P. J., Menzel, S., Furuta, H., Vaxillaire, M., Southam, L., Cox, R., Lathrop, M. G., Boriraj, V. V., et al. (1996) · Nature · doi:10.1038/384455a0 · Cited by 1,610 · see citing works
Self-citationPontoglio, M., Barra, J., Hadchouel, M., Doyen, A., Kress, C., Poggi-Bach, J., Babinet, C., & Yaniv, M. (1996) · Cell · doi:10.1016/s0092-8674(00)81033-8 · Cited by 580 · see citing works
Self-citationInteraction of a Liver-Specific Nuclear Factor with the Fibrinogen and α 1 -Antitrypsin Promoters
Courtois, G., Morgan, J. G., Campbell, L. A., Fourel, G., & Crabtree, G. R. (1987) · Science · doi:10.1126/science.3499668 · Cited by 460 · see citing works
Compensatory Growth of Pancreatic β-Cells in Adult Rats After Short-Term Glucose Infusion
Bonner‐Weir, S., Deery, D. J., Leahy, J. L., & Weir, G. C. (1989) · Diabetes · doi:10.2337/diab.38.1.49 · Cited by 444 · see citing works
Self-citationFactors involved in control of tissue-specific expression of albumin gene
Cereghini, S., Raymondjean, M., Carrancá, A. G., Herbomel, P., & Yaniv, M. (1987) · Cell · doi:10.1016/0092-8674(87)90036-5 · Cited by 353 · see citing works
Self-citationThe Role of Cis-Acting Promoter Elements in Tissue-Specific Albumin Gene Expression
Maire, P., Wuarin, J., & Schibler, U. (1989) · Science · doi:10.1126/science.2711183 · Cited by 309 · see citing works
Byrne, M. M., Sturis, J., Menzel, S., Yamagata, K., Fajans, S. S., Dronsfield, M. J., Bain, S. C., Hattersley, A. T., Velho, G., Froguel, P., et al. (1996) · Diabetes · doi:10.2337/diab.45.11.1503 · Cited by 259 · see citing works
Self-citationCharacterization of the MODY3 phenotype. Early-onset diabetes caused by an insulin secretion defect.
Lehto, M. J., Tuomi, T., Mahtani, M. M., Widén, E., Forsblom, C. M., Sarelin, L., Gullström, M., Isomaa, B., Lehtovirta, M., Hyrkkö, A., et al. (1997) · Journal of Clinical Investigation · doi:10.1172/jci119199 · Cited by 196 · see citing works
Montaña, E., Bonner‐Weir, S., & Weir, G. C. (1993) · Journal of Clinical Investigation · doi:10.1172/jci116297 · Cited by 193 · see citing works
Self-citationTronche, F., Ringeisen, F. P., BLUMENFELD, M. L., Yaniv, M., & Pontoglio, M. (1997) · Journal of Molecular Biology · doi:10.1006/jmbi.1996.0760 · Cited by 178 · see citing works
Self-citationEmens, L. A., Landers, D. W., & Moss, L. G. (1992) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.89.16.7300 · Cited by 142 · see citing works
Maturity‐onset diabetes of the young (MODY)
Fajans, S. S. (1989) · Diabetes/Metabolism Reviews · doi:10.1002/dmr.5610050705 · Cited by 130 · see citing works
Sreenan, S., Sturis, J., Pugh, W., Burant, C., & Polonsky, K. S. (1996) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1996.271.4.e742 · Cited by 125 · see citing works
Self-citationMcCulloch, D. K., Koerker, D. J., Kahn, S. E., Bonner‐Weir, S., & Palmer, J. P. (1991) · Diabetes · doi:10.2337/diab.40.6.673 · Cited by 115 · see citing works
Self-citationRegulation of Pancreatic β-Cell Mass in Vivo
Bonner‐Weir, S. (1994) · Elsevier eBooks · doi:10.1016/b978-0-12-571149-4.50008-8 · Cited by 112 · see citing works
Self-citationVoltage-dependent intracellular calcium release from mouse islets stimulated by glucose
Roe, M. W., Lancaster, M. E., Mertz, R. J., Worley, J. F., & Dukes, I. D. (1993) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)82156-1 · Cited by 108 · see citing works
Self-citationCompensatory growth of pancreatic beta-cells in adult rats after short-term glucose infusion
Bonner‐Weir, S., Deery, D., Leahy, J. L., & Weir, G. C. (1989) · Diabetes · doi:10.2337/diabetes.38.1.49 · Cited by 107 · see citing works
Self-citationByrne, M. M., Sturis, J., Menzel, S., et al. (1996) · Diabetes · doi:10.2337/diabetes.45.11.1503 · Cited by 78 · see citing works
Pontoglio, M., Faust, D. M., Doyen, A., Yaniv, M., & Weiss, M. C. (1997) · Molecular and Cellular Biology · doi:10.1128/mcb.17.9.4948 · Cited by 74 · see citing works
Self-citationAlterations in pulsatile insulin secretion in the Zucker diabetic fatty rat
Sturis, J., Pugh, W. L., Tang, J. A., Ostrega, D., Polonsky, J. S., & Polonsky, K. S. (1994) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1994.267.2.e250 · Cited by 63 · see citing works
Self-citationBrooks, A. R., & Levy-Wilson, B. (1992) · Molecular and Cellular Biology · doi:10.1128/mcb.12.3.1134 · Cited by 48 · see citing works
Maturity onset diabetes of the young (MODY)
Fajan, S. S., Bell, G. I., Bowden, D. W., Halter, J. B., & Polonsky, K. S. (1996) · Diabetic Medicine · doi:10.1002/dme.1996.13.s6.90 · Cited by 21 · cited 1× · see citing works
“Maturity-onset diabetes of the young (MODY) 1 is an autosomal dominant form of non–insulin-dependent diabetes mellitus in which affected subjects develop hyperglycemia generally before the age of 25 yr (1, 2).”
BackgroundSelf-citationThe human prothrombin gene: transcriptional regulation in HepG2 cells
Bancroft, J. D., McDowell, S. A., & Degen, S. J. F. (1992) · Biochemistry · doi:10.1021/bi00164a025 · Cited by 18 · see citing works
Glucokinase and MODY: from the Gene to the Disease
Froguel, P. (1996) · Diabetic Medicine · doi:10.1002/dme.1996.13.s6.96 · Cited by 9 · see citing works
Self-citationBrooks, A. R., & Levy-Wilson, B. (1992) · Molecular and Cellular Biology · doi:10.1128/mcb.12.3.1134-1148.1992 · Cited by 7 · see citing works
Flagged first, then by citations
Research works printed but not linked: 1
- Weibel, E.R. 1978. Stereologic methods. In Practical Methods for Bio- logic Morphometry. Vol 1. Academic Press Ltd., London. 101-161.
Cited by
Sorted by citations
Molecular mechanisms and clinical pathophysiology of maturity-onset diabetes of the young
Fajans, S. S., Bell, G. I., & Polonsky, K. S. (2001) · New England Journal of Medicine · doi:10.1056/nejmra002168 · Cited by 1,123 · see citing works
Self-citationPancreatic regulation of glucose homeostasis.
Röder, P. V., Wu, B., Liu, Y., & Han, W. (2016) · Experimental & Molecular Medicine · doi:10.1038/emm.2016.6 · Cited by 985 · see citing works
Genetic cause of hyperglycaemia and response to treatment in diabetes
Pearson, E. R., Starkey, B. J., Powell, R. J., Gribble, F. M., Clark, P. M., & Hattersley, A. T. (2003) · The Lancet · doi:10.1016/s0140-6736(03)14571-0 · Cited by 607 · see citing works
Regulation of pancreatic β-cell growth and survival by the serine/threonine protein kinase Akt1/PKBα
Tuttle, R. L., Gill, N. S., Pugh, W., Lee, J.-P., Koeberlein, B., Furth, E. E., Polonsky, K. S., Naji, A., & Birnbaum, M. J. (2001) · Nature Medicine · doi:10.1038/nm1001-1133 · Cited by 511 · see citing works
“The pancreas was perfused using a slightly modified protocol as describe”
MethodSelf-citationDiabetes mellitus and genetically programmed defects in β-cell function
Bell, G. I., & Polonsky, K. S. (2001) · Nature · doi:10.1038/414788a · Cited by 475 · see citing works
“In mice lacking the gene for HNF-1α, β-cell mass fails to increase despite the presence of hyperglycaemia, which suggests that this transcription factor may regulate β-cell mas”
BackgroundSelf-citationMitochondrial function in normal and diabetic β-cells
Maechler, P., & Wollheim, C. B. (2001) · Nature · doi:10.1038/414807a · Cited by 519 · see citing works
“Suppression of the HNF-1α gene in mice results in diabetes and impairment of glucose-induced insulin secretion assessed in vitro”
BackgroundTranscription Factors in Liver Development, Differentiation, and Regeneration
Costa, R. H., Kalinichenko, V. V., Holterman, A. L., & Wang, X. (2003) · Hepatology · doi:10.1016/j.hep.2003.09.034 · Cited by 408 · see citing works
Minireview: transcriptional regulation in pancreatic development.
Habener, J., Kemp, D. M., & Thomas, M. K. (2005) · Endocrinology · doi:10.1210/en.2004-1576 · Cited by 437 · see citing works
Reduction in Pancreatic Transcription Factor PDX-1 Impairs Glucose-stimulated Insulin Secretion
Briššová, M., Shiota, M., Nicholson, W. E., GANNON, M. A., Knobel, S. M., Piston, D. W., Wright, C. V. E., & Powers, A. C. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m111272200 · Cited by 376 · see citing works
Bile system morphogenesis defects and liver dysfunction upon targeted deletion of HNF1β
Coffinier, C., Gresh, L., Fiette, L., Tronche, F., Schütz, G., Babinet, C., Pontoglio, M., Yaniv, M., & Barra, J. (2002) · Development · doi:10.1242/dev.129.8.1829 · Cited by 354 · see citing works
Self-citationGene expression cascades in pancreatic development
Wilson, M. E., Scheel, D., & German, M. S. (2002) · Mechanisms of Development · doi:10.1016/s0925-4773(02)00333-7 · Cited by 354 · see citing works
Increased islet apoptosis in Pdx1+/- mice.
Johnson, J. D., Ahmed, N. T., Luciani, D., Han, Z.-Q., Tran, H. D., Fujita, J., Misler, S., Edlund, H., & Polonsky, K. (2003) · Journal of Clinical Investigation · doi:10.1172/jci16537 · Cited by 348 · see citing works
“To obtain pancreatic islets, pancreata were removed and islets were isolated by collagenase digestion using a protocol adapted (21) from one described by Lacy and Kostianovsky (22).”
MethodInfluentialSelf-citationFamilial Renal Glucosuria and SGLT2
Santer, R., & Calado, J. (2009) · Clinical Journal of the American Society of Nephrology · doi:10.2215/cjn.04010609 · Cited by 341 · see citing works
“HNF1 / homozygous mice, compared with wild-type or heterozygous healthy littermates, displayed deficient insulin secretion and hyperglycemia (34); however, plasma glucose concentrations were lower than expected in light of the severity of the insulin secretory defect, probably secondary to the associated glucose resor…”
BackgroundInsulin Signaling in α Cells Modulates Glucagon Secretion In Vivo
Kawamori, D., Kurpad, A. J., Hu, J., Liew, C. W., Shih, J. L., Ford, E. L., Herrera, P. L., Polonsky, K. S., McGuinness, O. P., & Kulkarni, R. N. (2009) · Cell Metabolism · doi:10.1016/j.cmet.2009.02.007 · Cited by 316 · see citing works
“Insulin secretion from the in situ-perfused pancreas The pancreas was perfused in situ in a humidified temperature-controlled chamber using a modification of a protocol described previously (Pontoglio et al., 1998).”
Self-citationTargeted Overactivity of β Cell KATP Channels Induces Profound Neonatal Diabetes
Koster, J. C., Marshall, B. A., Ensor, N. J., Corbett, J. A., & Nichols, C. G. (2000) · Cell · doi:10.1016/s0092-8674(00)80701-1 · Cited by 287 · see citing works
Ryffel, G. (2001) · Journal of Molecular Endocrinology · doi:10.1677/jme.0.0270011 · Cited by 268 · see citing works
“A more detailed analysis revealed defective insulin secretion in the pancreatic -cells of HNF1 -deficient mice, but no impairment was found in heterozygous animals (Dukes et al. 1998, Pontoglio et al. 1998, Pontoglio 2000).”
BackgroundRegulation of the Pancreatic Pro-Endocrine Gene Neurogenin3
Lee, J. C., Smith, S. B., Watada, H., Lin, J., Scheel, D., Wang, J., Mirmira, R. G., & German, M. S. (2001) · Diabetes · doi:10.2337/diabetes.50.5.928 · Cited by 258 · see citing works
“However, it has been proposed that the diabetes in these animals and (by inference) the diabetes seen in humans with heterozygous mutations in HNF-1a results from defects in glucose sensing by the b-cell, rather than decreased islet mass (42).”
BackgroundA transcription factor regulatory circuit in differentiated pancreatic cells
Boj, S. F., Párrizas, M., Maestro, M. A., & Ferrer, J. P. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.241349398 · Cited by 253 · see citing works
Calcium release channel RyR2 regulates insulin release and glucose homeostasis
Santulli, G., Pagano, G., Sardu, C., Xie, W., Reiken, S. R., D’Ascia, S. L., Cannone, M., Marziliano, N., Trimarco, B., Guise, T. A., et al. (2015) · Journal of Clinical Investigation · doi:10.1172/jci79273 · Cited by 239 · see citing works
The MODY1 gene HNF-4α regulates selected genes involved in insulin secretion
Gupta, R. K., Vatamaniuk, M. Z., Lee, C. S., Flaschen, R. C., Fulmer, J. T., Matschinsky, F. M., Duncan, S. A., & Kaestner, K. H. (2005) · Journal of Clinical Investigation · doi:10.1172/jci22365 · Cited by 239 · see citing works
“For example, disruption of HNF-1α in mice results in defective glucose sensing and the failure of isolated islets from these animals to properly respond to glucose (21, 22).”
BackgroundEssential role for the homeoprotein vHNF1/HNF1β in visceral endoderm differentiation
Coffinier, C., Thépot, D., Babinet, C., Yaniv, M., & Barra, J. (1999) · Development · doi:10.1242/dev.126.21.4785 · Cited by 239 · see citing works
Self-citationMitochondrial dysfunction in pancreatic β cells
Supale, S., Li, N., Brun, T., & Maechler, P. (2012) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2012.06.002 · Cited by 231 · see citing works
The molecular functions of hepatocyte nuclear factors – In and beyond the liver
Lau, H. H., Ng, N. H. J., Loo, L. S. W., Jasmen, J. B., & Teo, A. K. K. (2018) · Journal of Hepatology · doi:10.1016/j.jhep.2017.11.026 · Cited by 250 · see citing works
Chen, J., Hui, S. T. Y., Couto, F. M., Mungrue, I. N., Davis, D. B., Attie, A., Lusis, A. J., Davis, R. A., & Shalev, A. (2008) · The FASEB Journal · doi:10.1096/fj.08-111690 · Cited by 226 · see citing works
Bernal-Mizrachi, E., Fátrai, S., Johnson, J. D., Ohsugi, M., Otani, K., Han, Z.-Q., Polonsky, K., & Permutt, M. (2004) · Journal of Clinical Investigation · doi:10.1172/jci20016 · Cited by 236 · see citing works
“experiments were carried out as described previously (39).”
Self-citationColclough, K., Bellanné‐Chantelot, C., Saint‐Martin, C., Flanagan, S. E., & Ellard, S. (2013) · Human Mutation · doi:10.1002/humu.22279 · Cited by 224 · see citing works
“Heterozygous HNF1A and HNF4A mutations are causative of the MODY phenotypes in humans, but mice with defects in a single copy of their Hnf1a or Hnf4a gene do not exhibit the impairments to glucose tolerance and insulin secretion or the renal glycosuria seen in humans, and are phenotypically indistinguishable from thei…”
BackgroundShih, D. Q., Screenan, S., Munoz, K. N., Philipson, L., Pontoglio, M., Yaniv, M., Polonsky, K. S., & Stoffel, M. (2001) · Diabetes · doi:10.2337/diabetes.50.11.2472 · Cited by 222 · see citing works
“Previous physiological studies using pancreatic islets from Hnf-1 –deficient mice showed that -cell dysfunction in these animals is likely to result from its defective glycolytic signaling proximal to mitochondrial oxidation (27,28).”
InfluentialSelf-citationHNF1α controls renal glucose reabsorption in mouse and man
Pontoglio, M., Prié, D., Chéret, C., Doyen, A., Leroy, C., Froguel, P., Velho, G., Yaniv, M., & Friedlander, G. (2000) · EMBO Reports · doi:10.1093/embo-reports/kvd071 · Cited by 221 · see citing works
Self-citationTranscriptional networks controlling pancreatic development and beta cell function
Servitja, J., & Ferrer, J. (2004) · Diabetologia · doi:10.1007/s00125-004-1368-9 · Cited by 225 · see citing works
“Hnf1α−/− mice are viable, and have thus turned out to be a very fruitful model to understand the function of MODY transcription factors in beta cells [19, 20, 21, 145, 146, 147].”
BackgroundMaturity-onset diabetes of the young (MODY): current perspectives on diagnosis and treatment
Urakami, T. (2019) · Diabetes Metabolic Syndrome and Obesity · doi:10.2147/dmso.s179793 · Cited by 212 · see citing works
“HNF1a knockout mice develop diabetes consequent to defective glucoseinduced insulin secretion.(28,29) Mutations in HNF1a are the most frequent causes of MODY in Europe, North America, and some Asian countries.”
BackgroundBeta-cell mitochondria in the regulation of insulin secretion: a new culprit in Type II diabetes
Wollheim, C. B. (2000) · Diabetologia · doi:10.1007/s001250050044 · Cited by 191 · see citing works
Defective insulin secretion in pancreatic β cells lacking type 1 IGF receptor
Xuan, S., Kitamura, T., Nakae, J., Politi, K. A., Kido, Y., Fisher, P. E., Morroni, M., Cinti, S., White, M. F., Herrera, P. L., et al. (2002) · Journal of Clinical Investigation · doi:10.1172/jci15276 · Cited by 198 · see citing works
Calpains Play a Role in Insulin Secretion and Action
Sreenan, S., Zhou, Y.-P., Otani, K., Hansen, P. A., Currie, K., Pan, C., Lee, J.-P., Ostrega, D., Pugh, W., Horikawa, Y., et al. (2001) · Diabetes · doi:10.2337/diabetes.50.9.2013 · Cited by 180 · see citing works
“We measured [Ca(21)]i responses to glucose and other secretagogues using fura-2 as described (6).”
BackgroundMethodSelf-citationJung, D., Hagenbuch, B., Gresh, L., Pontoglio, M., Meier, P. J., & Kullak-Ublick, G. A. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m103988200 · Cited by 170 · see citing works
Self-citationYamagata, K., Nammo, T., Moriwaki, M., Ihara, A., Iizuka, K., Yang, Q., Satoh, T., Li, M., Uenaka, R., Okita, K., et al. (2002) · Diabetes · doi:10.2337/diabetes.51.1.114 · Cited by 167 · see citing works
Vaxillaire, M., & Froguel, P. (2008) · Endocrine Reviews · doi:10.1210/er.2007-0024 · Cited by 167 · see citing works
“This is in part linked to defective islet-cell glycolytic flux and is associated with decreased expression of Glut2 glucose transporter and L-type pyruvate kinase genes (39, 40).”
BackgroundSelf-citationDefective Pancreatic β-Cell Glycolytic Signaling in Hepatocyte Nuclear Factor-1α-deficient Mice
Dukes, I. D., Sreenan, S., Roe, M. W., Levisetti, M. G., Zhou, Y.-P., Ostrega, D., Bell, G. I., Pontoglio, M., Yaniv, M., Philipson, L. H., et al. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.38.24457 · Cited by 165 · see citing works
Self-citationContreras, J. L., Eckstein, C. P., Smyth, C. A., Sellers, M. T., Vilatobá, M., Bilbao, G., Rahemtulla, F. G., Young, C. J., Thompson, J. A., Chaudry, I. H., et al. (2003) · Diabetes · doi:10.2337/diabetes.52.12.2935 · Cited by 164 · see citing works
“Six hours after mechanical ventilation in animals with and without CNS injury, the pancreas was perfused in situ using a modified protocol described previously (14).”
MethodWang, H.-Y., Maechler, P., Hagenfeldt, K., & Wollheim, C. (1998) · EMBO Journal · doi:10.1093/emboj/17.22.6701 · Cited by 162 · see citing works
“In agreement with our results, Pontoglio et al. (1998) have recently reported that glucose-induced but not K -evoked [Ca2 ]i increase was diminished in HNF-1α-deficient mice.”
BackgroundResultInfluentialThe HNF-1 target Collectrin controls insulin exocytosis by SNARE complex formation
Fukui, K., Yang, Q., Cao, Y., Takahashi, N. K., Hatakeyama, H., Wang, H., Wada, J., Zhang, Y., Marselli, L., Nammo, T., et al. (2005) · Cell Metabolism · doi:10.1016/j.cmet.2005.11.003 · Cited by 152 · see citing works
“Earlier studies indicated that HNF-1a plays an important role in the multifactorial process of insulin secretion including glucose transport, glycolysis and mitochondrial oxidation (Pontoglio et al., 1998; Dukes et al., 1998; Yamagata et al., 2002; Wang et al., 1998, 2000; Yang et al., 2002).”
BackgroundAnimal models of type 2 diabetes with reduced pancreatic β-cell mass
Masiello, P. (2005) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2005.09.007 · Cited by 146 · see citing works
Hegele, R. A., Cao, H., Harris, S. B., Hanley, A. J., & Zinman, B. (1999) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.84.3.5528 · Cited by 144 · see citing works
“The decreased stimulation of glucose utilization, oxidation, and nonoxidative glucose disposal and the blunted suppression of endogenous glucose output that are seen in MODY3 patients with HNF1a mutations appear to result from insulinopenia, whereas insulin sensitivity appears to be intact in these subjects (25).”
BackgroundClinical features and treatment of maturity onset diabetes of the young (MODY)
Gardner, D. S.-L., & Tai, E. S. (2012) · Diabetes Metabolic Syndrome and Obesity · doi:10.2147/dmso.s23353 · Cited by 143 · see citing works
“The HNF1A gene consists of ten exons and studies of HNF1A knockout animals show a reduction in the key steps of glucose transport and metabolism.(23) In β-cell lines, mitochondrial metabolism also appears to be reduced.”
Párrizas, M., Maestro, M. A., Boj, S. F., Paniagua, A., Casamitjana, R., Gomis, R., Rivera, F., & Ferrer, J. P. (2001) · Molecular and Cellular Biology · doi:10.1128/mcb.21.9.3234-3243.2001 · Cited by 141 · see citing works
“These mice display glycosuria secondary to renal tubular dysfunction, and like humans with heterozygous mutations in the gene encoding HNF1-a, they develop overt diabetes (23, 30 ).”
BackgroundResultInfluentialServitja, J., Pignatelli, M., Maestro, M. Á., Cardalda, C. A., Boj, S. F., Lozano, J. J., Blanco, E., Lafuente, A., McCarthy, M. I., Sumoy, L., et al. (2009) · Molecular and Cellular Biology · doi:10.1128/mcb.01389-08 · Cited by 140 · see citing works
“Also consistent with previous studies, islet size in young Hnf1a / mice was decreased (50), although”
BackgroundResultInfluentialHui, H., & Perfetti, R. (2002) · European Journal of Endocrinology · doi:10.1530/eje.0.1460129 · Cited by 137 · see citing works
Pearson, E. R., Velho, G., Clark, P., Stride, A., Shepherd, M. H., Frayling, T. M., Bulman, M. P., Ellard, S., Froguel, P., & Hattersley, A. T. (2001) · Diabetes · doi:10.2337/diabetes.50.2007.s101 · Cited by 134 · see citing works
Self-citationMolecular targets of a human HNF1α mutation responsible for pancreatic β‐cell dysfunction
Wang, H., Antinozzi, P. A., Hagenfeldt, K. A., Maechler, P., & Wollheim, C. B. (2000) · The EMBO Journal · doi:10.1093/emboj/19.16.4257 · Cited by 133 · see citing works
Monogenic Diabetes: What It Teaches Us on the Common Forms of Type 1 and Type 2 Diabetes
Yang, Y., & Chan, L. (2016) · Endocrine Reviews · doi:10.1210/er.2015-1116 · Cited by 133 · see citing works
Hepatocyte Nuclear Factor 1, a Transcription Factor at the Crossroads of Glucose Homeostasis
Pontoglio, M. (2000) · Journal of the American Society of Nephrology · doi:10.1681/asn.v11suppl_2s140 · Cited by 129 · see citing works
Self-citationSoutoglou, E., Papafotiou, G., Katrakili, N., & Talianidis, I. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.275.17.12515 · Cited by 127 · see citing works
Harries, L. W., Ellard, S., Stride, A., Morgan, N. G., & Hattersley, A. T. (2006) · Human Molecular Genetics · doi:10.1093/hmg/ddl147 · Cited by 127 · see citing works
“Our data is in agreement with Tcf1 expression data from the mouse (21,29).”
BackgroundResultInfluentialSpecifying pancreatic endocrine cell fates.
Collombat, P., Hecksher-Sørensen, J., Serup, P., & Mansouri, A. (2006) · Mechanisms of Development · doi:10.1016/j.mod.2006.05.006 · Cited by 142 · see citing works
“1 – (Shih et al., 2001), 2 – (Pontoglio et al., 1998), 3 – (Coffinier et al., 1999), 4 – (Kaestner et al., 1999), 5 – (Ang and Rossant, 1994), 6 – (Weinstein et al., 1994), 7 – (Sund et al., 2001b), 8 – (Kaestner et al., 1998), 9 – (Shen et al., 2001), 10 – (Chen et al., 1994), 11 – (Duncan et al.,…”
BackgroundRegulation of Apolipoprotein M Gene Expression by MODY3 Gene Hepatocyte Nuclear Factor-1α
Richter, S., Shih, D. Q., Pearson, E. R., Wolfrum, C., Fajans, S. S., Hattersley, A. T., & Stoffel, M. (2003) · Diabetes · doi:10.2337/diabetes.52.12.2989 · Cited by 124 · see citing works
Hattersley, A. T., & Pearson, E. R. (2006) · Endocrinology · doi:10.1210/en.2006-0152 · Cited by 118 · see citing works
The Role of Hepatic Nuclear Factor 1α and PDX-1 in Transcriptional Regulation of the pdx-1 Gene
Gerrish, K., Cissell, M. A., & Stein, R. W. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m109244200 · Cited by 116 · see citing works
Pancreatic Development and Disease
Cano, D. A., Hebrok, M., & Zenker, M. (2007) · Gastroenterology · doi:10.1053/j.gastro.2006.12.054 · Cited by 114 · see citing works
Maestro, M. A., Cardalda, C. A., Boj, S. F., Luco, R. F., Servitja, J., & Ferrer, J. P. (2007) · Endocrine development · doi:10.1159/000109603 · Cited by 112 · see citing works
Molecular Genetics of Maturity-onset Diabetes of the Young
Froguel, P., & Velho, G. (1999) · Trends in Endocrinology and Metabolism · doi:10.1016/s1043-2760(98)00134-9 · Cited by 110 · see citing works
Self-citationMcCarthy, M. I. (2004) · Human Molecular Genetics · doi:10.1093/hmg/ddh057 · Cited by 108 · see citing works
Zhou, Y.-P., Pena, J. C., Roe, M. W., Mittal, A., Levisetti, M. G., Baldwin, A. C., Pugh, W., Ostrega, D., Ahmed, N. T., Bindokas, V. P., et al. (2000) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.2000.278.2.e340 · Cited by 108 · see citing works
Self-citationD'Angelo, A., Bluteau, O., García-González, M. Á., Gresh, L., Doyen, A., Garbay, S., Robine, S., & Pontoglio, M. (2010) · Development · doi:10.1242/dev.044420 · Cited by 105 · see citing works
“In fact, Hnf1a-deficient mice (Hnf1a–/–) are born normally, but suffer from hepatic, pancreatic and renal functional defects (Pontoglio et al., 1996; Pontoglio et al., 1997; Pontoglio et al., 1998; Lee et al., 1998; Pontoglio et al., 2001).”
BackgroundSelf-citationDiagnosis and Management of Maturity-Onset Diabetes of the Young
Timsit, J., Bellanné‐Chantelot, C., Dubois-Laforgue, D., & Velho, G. (2005) · Treatments in Endocrinology · doi:10.2165/00024677-200504010-00002 · Cited by 103 · see citing works
Self-citationOhsugi, M., CRAS-MÉNEUR, C. M. H., Zhou, Y., Bernal‐Mizrachi, E., Johnson, J. D., Luciani, D. S., Polonsky, K. S., & Permutt, M. A. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m411727200 · Cited by 99 · see citing works
Self-citationTranscription Factors in Islet Development and Physiology: Role of PDX‐1 in Beta‐Cell Function
Melloul, D. (2004) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1294.003 · Cited by 99 · see citing works
Pancreas development and diabetes
St‐Onge, L., Wehr, R., & Grusst, P. (1999) · Current Opinion in Genetics & Development · doi:10.1016/s0959-437x(99)80044-6 · Cited by 97 · see citing works
Wang, H.-Y., Gauthier, B. R., Hagenfeldt-Johansson, K., Iezzi, M., & Wollheim, C. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m111037200 · Cited by 104 · see citing works
Anatomy of a Homeoprotein Revealed by the Analysis of Human MODY3 Mutations
Vaxillaire, M., Abderrahmani, A., Boutin, P., Bailleul, B., Froguel, P., Yaniv, M., & Pontoglio, M. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.50.35639 · Cited by 95 · see citing works
Self-citationBacon, S., Kyithar, M. P., Rizvi, S. R., Donnelly, E., McCarthy, A., Burke, M., Colclough, K., Ellard, S., & Byrne, M. M. (2015) · Diabetic Medicine · doi:10.1111/dme.12992 · Cited by 94 · see citing works
Common variants in HNF-1 α and risk of type 2 diabetes
Holmkvist, J., Cervin, C., Lyssenko, V., Winckler, W., Anevski, D., Cilio, C., Almgren, P.-E., Berglund, G., Nilsson, P. M., Tuomilehto, J., et al. (2006) · Diabetologia · doi:10.1007/s00125-006-0450-x · Cited by 92 · see citing works
“It has also been suggested that HNF-1α might influence islet size and, indeed, the Hnf-1α mouse is characterised by decreased islet mass [37].”
BackgroundGlucagon-like peptide 1 receptor signaling influences topography of islet cells in mice
Ling, Z., Wu, D., Zambre, Y., Flamez, D., Drucker, D. J., PIPELEERS, D. G., & Schuit, F. C. (2001) · Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin · doi:10.1007/s004280000374 · Cited by 91 · see citing works
Dominant-negative mutant hepatocyte nuclear factor 1α induces diabetes in transgenic-cloned pigs
Umeyama, K., Watanabe, M., Saitô, H., Kurome, M., Tohi, S., Matsunari, H., Miki, K., & Nagashima, H. (2009) · Transgenic Research · doi:10.1007/s11248-009-9262-3 · Cited by 90 · see citing works
“HNF-1a knock-out mice exhibit a phenotype that lacks insulin secretion with severe renal dysfunction (Pontoglio et al. 1996, 1998).”
Purushotham, A., Xu, Q., Lu, J., Foley, J. F., Yan, X., Kim, D.-H., Kemper, J. K., & Li, X. (2012) · Molecular and Cellular Biology · doi:10.1128/mcb.05988-11 · Cited by 87 · see citing works
“Haploinsufficiency of HNF1 in humans (56) and knockout of HNF1 in mice led to the development of diabetes, renal Fanconi syndrome, hepatic dysfunction, and hypercholesterolemia (25, 38, 39).”
BackgroundA Genetic Switch in Pancreatic β-Cells
Ferrer, J. P. (2002) · Diabetes · doi:10.2337/diabetes.51.8.2355 · Cited by 89 · see citing works
“One apparent difference between HNF-1 null mutant mice and humans is the lack of a clear phenotype in heterozygous mice up to age 16 weeks (23,27).”
BackgroundResultInfluentialHepatocyte Nuclear Factor-1α Gene Mutations and Diabetes in Norway
Bjørkhaug, L., Sagen, J. V., Thorsby, P. M., Sövik, O., Molven, A., & Njølstad, P. R. (2003) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2002-020945 · Cited by 85 · see citing works
Akiyama, T. E. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m004388200 · Cited by 87 · see citing works
Cardenas-Diaz, F. L., Osorio-Quintero, C., Diaz-Miranda, M. A., Kishore, S., Leavens, K. F., Jobaliya, C. D., Stanescu, D. E., Ortiz-González, X., Yoon, C., Chen, C. S., et al. (2019) · Cell Stem Cell · doi:10.1016/j.stem.2019.07.007 · Cited by 82 · see citing works
“Another approach has been overexpression of a dominant negative form of HNF1A with phenotypes from this model being comparable to the HNF1A null model and include hyperglycemia, impaired insulin secretion, abnormal expression of genes related to β-cell function and loss of β-cell mass by apoptosis (Bonner et al. 2010;…”
BackgroundMethodEeckhoute, J., Moerman, E., Bouckenooghe, T., Lukowiak, B., Pattou, F. N., Formstecher, P., Kerr-Conte, J. A., Vandewalle, B., & Laine, B. (2003) · Endocrinology · doi:10.1210/en.2002-0024 · Cited by 85 · see citing works
Novel insights into genetics and clinics of the HNF1A-MODY
Valkovicova, T., Skopkova, M., Stanik, J., & Gasperikova, D. (2019) · Endocrine Regulations · doi:10.2478/enr-2019-0013 · Cited by 84 · see citing works
“Impaired B-cell glucose sensing is probably the result of reduced aerobic glycolysis and mitochondrial metabolism (Byrne et al. 1996; Dukes et al. 1998; Pontoglio et al. 1998).”
BackgroundMurakami, S., Nemazanyy, I., White, S. M., Chen, H., Nguyen, C. D. K., Graham, G. T., Saur, D., Pende, M., & Yi, C. (2019) · Developmental Cell · doi:10.1016/j.devcel.2019.07.022 · Cited by 83 · see citing works
“Endocrine progenitor markers Onecut1, NeuroG3 and NeuroD1 were also upregulated in long-term surviving Yap− cells in vitro and in regenerated KYYF pancreata, although Hnf1a, a transcription factor necessary for maintaining the homeostasis of differentiated endocrine cells (Pontoglio et al., 1998), was largely unaffect…”
BackgroundBonnefond, A., Lomberk, G. A., Buttar, N. S., Busiah, K., Vaillant, E., Lobbens, S., Yengo, L., Dechaume, A., Mignot, B., Simon, A., et al. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.215822 · Cited by 82 · see citing works
Self-citationZeng, X. Y., Lin, Y., Yin, C., Zhang, X., Ning, B., Zhang, Q., Zhang, J., Qiu, L., Qin, X.-R., Chen, Y.-X., et al. (2010) · Hepatology · doi:10.1002/hep.24647 · Cited by 82 · see citing works
“, dramatic liver enlargement caused by an increased proliferation of hepatocytes and degeneration of individual hepatocytes).(13,14) On the other hand, it has been proven that the expression of HNF1a was decreased in chemically induced liver tumors in mice(15) and in human HCC tissues.”
BackgroundMany faces of monogenic diabetes
Schwitzgebel, V. (2014) · Journal of Diabetes Investigation · doi:10.1111/jdi.12197 · Cited by 82 · see citing works
Genetic Basis of Maturity-Onset Diabetes of the Young
Vaxillaire, M., & Froguel, P. (2006) · Endocrinology and Metabolism Clinics of North America · doi:10.1016/j.ecl.2006.02.009 · Cited by 81 · see citing works
Self-citationRegulation of the Liver Fatty Acid-binding Protein Gene by Hepatocyte Nuclear Factor 1α (HNF1α)
Akiyama, T. E., Ward, J. M., & Gonzalez, F. J. (2000) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)61487-0 · Cited by 82 · see citing works
The Human Islet: Mini-Organ With Mega-Impact
Walker, J. T., Saunders, D. C., Briššová, M., & Powers, A. C. (2021) · Endocrine Reviews · doi:10.1210/endrev/bnab010 · Cited by 80 · see citing works
Stancill, J. S., Cartailler, J., Clayton, H. W., O’Connor, J. T., Dickerson, M. T., Dadi, P. K., Osipovich, A. B., Jacobson, D. A., & Magnuson, M. A. (2017) · Diabetes · doi:10.2337/db16-1355 · Cited by 76 · see citing works
“Furthermore, because a gene knockout of Hnf1a results in b-cell failure and diabetes (56), a predicted decrease in its activity could explain the decrease in genes involved in b-cell function in Abcc8 b-cells.”
The Prevalence of the HNF-1α G319S Mutation in Canadian Aboriginal Youth With Type 2 Diabetes
Sellers, E. A. C., Triggs‐Raine, B. L., Greenberg, C. R., & Dean, H. (2002) · Diabetes Care · doi:10.2337/diacare.25.12.2202 · Cited by 75 · see citing works
“Evidence of decreased production and secretion of insulin in the HNF-1 ( / ) knockout mouse lends support to this proposed mechanism (3).”
BackgroundGenetic and clinical characteristics of maturity‐onset diabetes of the young
Giuffrida, F. M. A., & Reis, A. F. (2004) · Diabetes Obesity and Metabolism · doi:10.1111/j.1463-1326.2004.00399.x · Cited by 75 · see citing works
Low, B. S. J., Lim, C. S., Ding, S. S. L., Tan, Y. S., Ng, N. H. J., Krishnan, V. G., Ang, S. F., Neo, C. W. Y., Verma, C. S., Hoon, S. S., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-22843-4 · Cited by 74 · see citing works
HNF1A：From Monogenic Diabetes to Type 2 Diabetes and Gestational Diabetes Mellitus
Li, L., Jiang, B., & Sun, L. (2022) · Frontiers in Endocrinology · doi:10.3389/fendo.2022.829565 · Cited by 72 · see citing works
Wice, B. M., Wang, S., Crimmins, D. L., Diggs‐Andrews, K. A., Althage, M. C., Ford, E. L., Tran, H. D., Ohlendorf, M. F., Griest, T. A., Wang, Q., et al. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.129304 · Cited by 74 · see citing works
Self-citationMaturity onset diabetes of the young: clinical characteristics, diagnosis and management.
Kavvoura, F. K., & Owen, K. R. (2012) · PubMed · Cited by 74 · see citing works
Wild, W., von Strandmann, E. P., Nastos, A., Senkel, S., Lingott, A., Bulman, M. P., Bingham, C., Ellard, S., Hattersley, A. T., & Ryffel, G. U. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.080010897 · Cited by 74 · see citing works
Research Resource: The Pdx1 Cistrome of Pancreatic Islets
Khoo, C., Yang, J., Weinrott, S. A., Kaestner, K. H., Naji, A., Schug, J., & Stoffers, D. A. (2012) · Molecular Endocrinology · doi:10.1210/me.2011-1231 · Cited by 71 · see citing works
Human islets expressing HNF1A variant have defective &bgr; cell transcriptional regulatory networks
Haliyur, R., Tong, X., Sanyoura, M., Shrestha, S., Lindner, J., Saunders, D. C., Aramandla, R., Poffenberger, G., Redick, S. D., Bottino, R., et al. (2018) · Journal of Clinical Investigation · doi:10.1172/jci121994 · Cited by 67 · see citing works
Hagenfeldt-Johansson, K. A., Herrera, P. L., Wang, H., Gjinovci, A., Ishihara, H., & Wollheim, C. B. (2001) · Endocrinology · doi:10.1210/endo.142.12.8592 · Cited by 72 · see citing works
“Although the HNF-1 -knockout mice have yielded important information (6, 11, 13, 22, 23), the pleiotropic impact of the disruption of the HNF-1 gene complicates their use for the study of glucose homeostasis.”
BackgroundResultEeckhoute, J. (2004) · Nucleic Acids Research · doi:10.1093/nar/gkh581 · Cited by 71 · see citing works
Growth factor control of pancreatic islet regeneration and function
Aßmann, A., Hinault, C., & Kulkarni, R. (2008) · Pediatric Diabetes · doi:10.1111/j.1399-5448.2008.00468.x · Cited by 71 · see citing works
Molecular mechanisms of congenital hyperinsulinism
Rahman, S. A., Nessa, A., & Hussain, K. (2015) · Journal of Molecular Endocrinology · doi:10.1530/jme-15-0016 · Cited by 69 · see citing works
“Though the loss of HNF1-a function does inevitably cause insulin dysregulation as shown using Hnf1a-null mice (Pontoglio et al. 1998), the exact mechanism is unknown.”
Background
- 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 › Surgery › 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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
