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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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MethodInfluentialSelf-citationFamilial Renal Glucosuria and SGLT2
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“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
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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
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“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
“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 251
Calcium release channel RyR2 regulates insulin release and glucose homeostasis
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The MODY1 gene HNF-4α regulates selected genes involved in insulin secretion
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“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
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 247
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
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Self-citationColclough, K., Bellanné‐Chantelot, C., Saint‐Martin, C., Flanagan, S. E., & Ellard, S. (2013) · Human Mutation · doi:10.1002/humu.22279 · Cited by 229
“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
“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
Self-citationTranscriptional networks controlling pancreatic development and beta cell function
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“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
“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.”
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Wollheim, C. B. (2000) · Diabetologia · doi:10.1007/s001250050044 · Cited by 192
Defective insulin secretion in pancreatic β cells lacking type 1 IGF receptor
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Calpains Play a Role in Insulin Secretion and Action
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“We measured [Ca(21)]i responses to glucose and other secretagogues using fura-2 as described (6).”
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“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
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
“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).”
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“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.”
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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
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“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)
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“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
“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 145
“Also consistent with previous studies, islet size in young Hnf1a / mice was decreased (50), although”
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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
Self-citationMolecular targets of a human HNF1α mutation responsible for pancreatic β‐cell dysfunction
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Hepatocyte Nuclear Factor 1, a Transcription Factor at the Crossroads of Glucose Homeostasis
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“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 132
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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
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The Role of Hepatic Nuclear Factor 1α and PDX-1 in Transcriptional Regulation of the pdx-1 Gene
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Pancreatic Development and Disease
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Molecular Genetics of Maturity-onset Diabetes of the Young
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“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
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
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
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
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
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
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
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 95
“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 95
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
“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
“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
“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
Akiyama, T. E. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m004388200 · Cited by 87
Cardenas‐Diaz, F. L., Osorio-Quintero, C., Diaz‐Miranda, M. A., Kishore, S., Leavens, K. F., Jobaliya, C., Stanescu, D. E., Ortiz-Gonzalez, X. R., Yoon, C. J., Chen, C. S., et al. (2019) · Cell stem cell · doi:10.1016/j.stem.2019.07.007 · Cited by 87
“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
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
“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
“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
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
“, 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 89
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
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
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 88
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
“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
“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
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
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 73
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
Self-citationMaturity onset diabetes of the young: clinical characteristics, diagnosis and management.
Kavvoura, F. K., & Owen, K. R. (2012) · PubMed · Cited by 71
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 73
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 72
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
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
“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
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 72
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
“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
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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