Mutation of the murine maturity-onset diabetes mellitus of the young (Mody) locus induces diabetes, but the effects of its homozygosity on the pancreas remain unknown. F2 mice were obtained by F1 (diabetic C57BL6 x normal Mus musculus castaneus) crosses. About 20% of the F2 progeny developed diabetes by 2 wk of age, 50% of the progeny were normal at 2 wk and developed diabetes between 5 and 8 wk of age, and the remaining 30% did not develop diabetes. Quantitative trait locus analysis using blood glucose levels of 118 F2 mice at 2 wk of age and 5-8 wk of age located Mody within 3 cM of D7Mit258. Histopathological investigation revealed hypoplastic islets (approximately 33% of that of wild-type mice) and a lower density of beta cells (approximately 20% of wild-type) with a reciprocal dominance of alpha cells (four times that of wild-type) in Mody homozygotes. Electron microscopic observations revealed a specific decrease in the number of insulin secretory granules and a lower density of beta cells. Ratios of insulin to glucagon contents confirmed specific decreases in insulin content: 0.01 for homozygotes, 0.54 for heterozygotes, and 1.11 for wild-type mice on day 14. These results suggest that Mody is involved in both islet growth and beta cell function.
T Kayo, A Koizumi
Title and authors | Publication | Year |
---|---|---|
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Contribution of animal models to diabetes research: Its history, significance, and translation to humans
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Bone | 2021 |
Alterations in β-Cell Sphingolipid Profile Associated with ER Stress and iPLA2β: Another Contributor to β-Cell Apoptosis in Type 1 Diabetes
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2020 | |
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Experimental biology and medicine (Maywood, N.J.) | 2020 |
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In utero exposure to maternal diabetes impairs nephron progenitor differentiation
DM Cerqueira, SL Hemker, AJ Bodnar, DM Ortiz, FO Oladipupo, E Mukherjee, Z Gong, C Appolonia, R Muzumdar, S Sims-Lucas, J Ho |
American journal of physiology. Renal physiology | 2019 |
Biosynthesis, structure, and folding of the insulin precursor protein
M Liu, MA Weiss, A Arunagiri, J Yong, N Rege, J Sun, L Haataja, RJ Kaufman, P Arvan |
Diabetes, obesity & metabolism | 2018 |
Inhibition of mTORC1 by ER stress impairs neonatal β-cell expansion and predisposes to diabetes in the Akita mouse
Y Riahi, T Israeli, R Yeroslaviz, S Chimenez, D Avrahami, M Stolovich-Rain, I Alter, M Sebag, N Polin, E Bernal-Mizrachi, Y Dor, E Cerasi, G Leibowitz |
eLife | 2018 |
Insulin mutations impair beta-cell development in a patient-derived iPSC model of neonatal diabetes
D Balboa, J Saarimäki-Vire, D Borshagovski, M Survila, P Lindholm, E Galli, S Eurola, J Ustinov, H Grym, H Huopio, J Partanen, K Wartiovaara, T Otonkoski |
eLife | 2018 |
β-cell-specific overexpression of adiponectin receptor 1 does not improve diabetes mellitus in Akita mice
J Choi, H Kobayashi, H Okuda, KH Harada, M Takeda, H Fujimoto, S Yamane, D Tanaka, S Youssefian, N Inagaki, A Koizumi, V Sánchez-Margalet |
PloS one | 2018 |
Misfolded proinsulin in the endoplasmic reticulum during development of beta cell failure in diabetes: Diabetogenic misfolding of proinsulin
A Arunagiri, L Haataja, CN Cunningham, N Shrestha, B Tsai, L Qi, M Liu, P Arvan |
Annals of the New York Academy of Sciences | 2018 |
Pulmonary Vein Ganglia Are Remodeled in the Diabetic Heart
G Bassil, M Chang, A Pauza, JD Vera, A Tsalatsanis, BG Lindsey, SF Noujaim |
Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease | 2018 |
Endoplasmic reticulum stress and eIF2α phosphorylation: The Achilles heel of pancreatic β cells
M Cnop, S Toivonen, M Igoillo-Esteve, P Salpea |
Molecular Metabolism | 2017 |
Effects of fetal exposure to high-fat diet or maternal hyperglycemia on L-arginine and nitric oxide metabolism in lung
C Grasemann, R Herrmann, J Starschinova, M Gertsen, MR Palmert, H Grasemann |
Nutrition and Diabetes | 2017 |
QRS/T-Wave and Calcium Alternans in a Type I Diabetic Mouse Model for Spontaneous Post Myocardial Infarction Ventricular Tachycardia: A Mechanism for the Antiarrhythmic Effect of Statins
H Jin, CM Welzig, M Aronovitz, F Noubary, R Blanton, B Wang, M Rajab, A Albano, MS Link, SF Noujaim, HJ Park, JB Galper |
Heart Rhythm | 2017 |
“Statins Protect Against Arrhythmogenic Calcium Alternans in the Post-MI Diabetic Heart: Pleiotropy on Steroids”
RL Verrier |
Heart Rhythm | 2017 |
Hyperglucagonemia in an animal model of insulin- deficient diabetes: what therapy can improve it?
F Barbetti, C Colombo, L Haataja, C Cras-Méneur, S Bernardini, P Arvan |
Clinical Diabetes and Endocrinology | 2016 |
A prominent role of PDIA6 in processing of misfolded proinsulin
DG Gorasia, NL Dudek, H Safavi-Hemami, RA Perez, RB Schittenhelm, PM Saunders, S Wee, JE Mangum, MJ Hubbard, AW Purcell |
Biochimica et Biophysica Acta (BBA) - Proteins & Proteomics | 2016 |
Insulin demand regulates beta cell proliferation via the UPR
Rohit Sharma, Amy O'Donnell, Rachel Stamateris, Binh Ha, Karen McCloskey, Paul Reynolds, Peter Arvan, Laura Alonso |
Journal of Clinical Investigation | 2015 |
Group VIA Phospholipase A 2 (iPLA 2 β) Modulates Bcl-x 5′-Splice Site Selection and Suppresses Anti-apoptotic Bcl-x(L) in β-Cells
SE Barbour, PT Nguyen, M Park, B Emani, X Lei, M Kambalapalli, JC Shultz, D Wijesinghe, CE Chalfant, S Ramanadham |
The Journal of biological chemistry | 2015 |
Altered parasympathetic nervous system regulation of the sinoatrial node in Akita diabetic mice
PS Krishnaswamy, EE Egom, M Moghtadaei, HJ Jansen, J Azer, O Bogachev, M Mackasey, C Robbins, RA Rose |
Journal of Molecular and Cellular Cardiology | 2015 |
Glycogen Synthase Kinase-3 Inhibition Ameliorates Cardiac Parasympathetic Dysfunction in Type 1 Diabetic Akita Mice
Y Zhang, CM Welzig, KL Picard, C Du, B Wang, JQ Pan, JM Kyriakis, MJ Aronovitz, WC Claycomb, RM Blanton, HJ Park, JB Galper |
Diabetes | 2014 |
Interactive network analysis of the plasma amino acids profile in a mouse model of hyperglycemia
T Tanaka, T Mochida, Y Maki, Y Shiraki, H Mori, S Matsumoto, K Shimbo, T Ando, K Nakamura, F Endo, M Okamoto |
SpringerPlus | 2013 |
Genetic complexity in a Drosophila model of diabetes-associated misfolded human proinsulin
SY Park, MZ Ludwig, NA Tamarina, BZ He, SH Carl, DA Dickerson, L Barse, B Arun, CL Williams, CM Miles, LH Philipson, DF Steiner, GI Bell, M Kreitman |
Genetics | 2013 |
Increased inducibility of ventricular tachycardia and decreased heart rate variability in a mouse model for type 1 diabetes: effect of pravastatin
M Rajab, H Jin, CM Welzig, A Albano, M Aronovitz, Y Zhang, HJ Park, MS Link, SF Noujaim, JB Galper |
American journal of physiology. Heart and circulatory physiology | 2013 |
Involvement of ASK1–p38 pathway in the pathogenesis of diabetes triggered by pancreatic ß cell exhaustion
K Yamaguchi, K Takeda, H Kadowaki, I Ueda, Y Namba, Y Ouchi, H Nishitoh, H Ichijo |
Biochimica et Biophysica Acta (BBA) - General Subjects | 2013 |
Deletion of C/EBP homologous protein (Chop) in C57Bl/6 mice dissociates obesity from insulin resistance
M Maris, L Overbergh, C Gysemans, A Waget, AK Cardozo, E Verdrengh, JP Cunha, T Gotoh, M Cnop, DL Eizirik, R Burcelin, C Mathieu |
Diabetologia | 2012 |
Transgenic zebrafish model of the C43G human insulin gene mutation
SC Eames, MD Kinkel, S Rajan, VE Prince, LH Philipson |
Journal of Diabetes Investigation | 2012 |
Proinsulin Atypical Maturation and Disposal Induces Extensive Defects in Mouse Ins2+/Akita β-Cells
Q Yuan, W Tang, X Zhang, JA Hinson, C Liu, K Osei, J Wang, M Gasset |
PloS one | 2012 |
Loss of TIMP3 selectively exacerbates diabetic nephropathy
R Basu, J Lee, Z Wang, VB Patel, D Fan, SK Das, GC Liu, R John, JW Scholey, GY Oudit, Z Kassiri |
American journal of physiology. Renal physiology | 2012 |
Hyperglycemia and xerostomia are key determinants of tooth decay in type 1 diabetic mice
CK Yeh, SE Harris, S Mohan, D Horn, R Fajardo, YH Chun, J Jorgensen, M MacDougall, S Abboud-Werner |
Laboratory Investigation | 2012 |
Diabetic modifier QTL, Dbm4, affecting elevated fasting blood glucose concentrations in congenic mice
S Takeshita, S Kitayama, T Suzuki, M Moritani, H Inoue, M Itakura |
Genes & Genetic Systems | 2012 |
Parental diabetes: the Akita mouse as a model of the effects of maternal and paternal hyperglycemia in wildtype offspring
C Grasemann, MJ Devlin, PA Rzeczkowska, R Herrmann, B Horsthemke, BP Hauffa, M Grynpas, C Alm, ML Bouxsein, MR Palmert |
PloS one | 2012 |
Bhlhe40, a potential diabetic modifier gene on Dbm1 locus, negatively controls myocyte fatty acid oxidation
S Takeshita, T Suzuki, S Kitayama, M Moritani, H Inoue, M Itakura |
Genes & Genetic Systems | 2012 |
Parental Diabetes: The Akita Mouse as a Model of the Effects of Maternal and Paternal Hyperglycemia in Wildtype Offspring
C Grasemann, MJ Devlin, PA Rzeczkowska, R Herrmann, B Horsthemke, BP Hauffa, M Grynpas, C Alm, ML Bouxsein, MR Palmert, AE Toland |
PloS one | 2012 |
Loss of TIMP3 selectively exacerbates diabetic nephropathy
R Basu, J Lee, Z Wang, VB Patel, D Fan, SK Das, GC Liu, R John, JW Scholey, GY Oudit, Z Kassiri |
American journal of physiology. Renal physiology | 2012 |
Insulin gene mutations and diabetes
M Nishi, K Nanjo |
Journal of Diabetes Investigation | 2011 |
Hyperglycemic Ins2AkitaLdlr−/− mice show severely elevated lipid levels and increased atherosclerosis: a model of type 1 diabetic macrovascular disease[S]
C Zhou, B Pridgen, N King, J Xu, JL Breslow |
Journal of lipid research | 2011 |
Endoplasmic reticulum stress and pancreatic beta cell death
SG Fonseca, J Gromada, F Urano |
Trends in endocrinology and metabolism: TEM | 2011 |
Time-dependent changes in the plasma amino acid concentration in diabetes mellitus
T Mochida, T Tanaka, Y Shiraki, H Tajiri, S Matsumoto, K Shimbo, T Ando, K Nakamura, M Okamoto, F Endo |
Molecular Genetics and Metabolism | 2011 |
A Model of Threshold Behavior Reveals Rescue Mechanisms of Bystander Proteins in Conformational Diseases
CI Sandefur, S Schnell |
Biophysical Journal | 2011 |
Apelin alleviates diabetes-associated endoplasmic reticulum stress in the pancreas of Akita mice
H Chen, C Zheng, X Zhang, J Li, J Li, L Zheng, K Huang |
Peptides | 2011 |
Long-term renal changes in the liver-specific glucokinase knockout mouse: implications for renal disease in maturity-onset diabetes of the young 2
Y Gu, Y Mao, H Li, S Zhao, Y Yang, H Gao, J Yu, X Zhang, DM Irwin, G Niu, H Tan |
Translational Research | 2011 |
Hyperglycemic Ins2 Akita Ldlr −/− mice show severely elevated lipid levels and increased atherosclerosis: a model of type 1 diabetic macrovascular disease
C Zhou, B Pridgen, N King, J Xu, JL Breslow |
Journal of lipid research | 2011 |
Mutant INS-gene induced diabetes of youth: proinsulin cysteine residues impose dominant-negative inhibition on wild-type proinsulin transport
M Liu, L Haataja, J Wright, NP Wickramasinghe, QX Hua, NF Phillips, F Barbetti, MA Weiss, P Arvan |
PloS one | 2010 |
A link between endoplasmic reticulum stress-induced β-cell apoptosis and the group VIA Ca2+-independent phospholipase A2 (iPLA2β)
X Lei, S Zhang, B Emani, SE Barbour, S Ramanadham |
Diabetes, Obesity and Metabolism | 2010 |
Proinsulin misfolding and diabetes: Mutant INS gene-induced Diabetes of Youth
M Liu, I Hodish, L Haataja, R Lara-Lemus, G Rajpal, J Wright, P Arvan |
Trends in endocrinology and metabolism: TEM | 2010 |
The binary switch that controls the life and death decisions of ER stressed beta cells
CM Oslowski, F Urano |
Current Opinion in Cell Biology | 2010 |
Group VIA Ca2+-independent phospholipase A2 (iPLA2β) and its role in β-cell programmed cell death
X Lei, SE Barbour, S Ramanadham |
Biochimie | 2010 |
Toward a More Rational Field-Genetic Epidemiology
A KOIZUMI |
Nippon Eiseigaku Zasshi (Japanese Journal of Hygiene) | 2010 |
Role of SREBP-1 in the development of parasympathetic dysfunction in the hearts of type 1 diabetic Akita mice
HJ Park, Y Zhang, C Du, CM Welzig, C Madias, MJ Aronovitz, SP Georgescu, I Naggar, B Wang, YB Kim, RO Blaustein, RH Karas, R Liao, CE Mathews, JB Galper |
Circulation research | 2009 |
Misfolded proinsulin affects bystander proinsulin in neonatal diabetes
I Hodish, M Liu, G Rajpal, D Larkin, RW Holz, A Adams, L Liu, P Arvan |
The Journal of biological chemistry | 2009 |
Spontaneous development of endoplasmic reticulum stress that can lead to diabetes mellitus is associated with higher calcium-independent phospholipase A2 expression: a role for regulation by SREBP-1
X Lei, S Zhang, SE Barbour, A Bohrer, EL Ford, A Koizumi, FR Papa, S Ramanadham |
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Use of erythrocyte adhesion assay to predict the risk of diabetic complications
Y Isaji, M Okochi, F Horio, H Honda |
Biochemical Engineering Journal | 2009 |
Spontaneous Development of Endoplasmic Reticulum Stress That Can Lead to Diabetes Mellitus Is Associated with Higher Calcium-independent Phospholipase A 2 Expression: A ROLE FOR REGULATION BY SREBP-1
X Lei, S Zhang, SE Barbour, A Bohrer, EL Ford, A Koizumi, FR Papa, S Ramanadham |
The Journal of biological chemistry | 2009 |
A new immunodeficient hyperglycaemic mouse model based on the Ins2 Akita mutation for analyses of human islet and beta stem and progenitor cell function
T Pearson, LD Shultz, J Lief, L Burzenski, B Gott, T Chase, O Foreman, AA Rossini, R Bottino, M Trucco, DL Greiner |
Diabetologia | 2008 |
Ablation of estrogen receptor alpha (ERα) prevents upregulation of POMC by leptin and insulin
M Hirosawa, M Minata, KH Harada, T Hitomi, A Krust, A Koizumi |
Biochemical and Biophysical Research Communications | 2008 |
Diabetes models by screen for hyperglycemia in phenotype-driven ENU mouse mutagenesis projects
B Aigner, B Rathkolb, N Herbach, MH de Angelis, R Wanke, E Wolf |
American journal of physiology. Endocrinology and metabolism | 2008 |
Diabetes Induces Rapid Suppression of Adaptive Immunity Followed by Homeostatic T-cell Proliferation
B Luo, WF Chan, SJ Lord, SA Nanji, RV Rajotte, AM Shapiro, CC Anderson |
Scandinavian Journal of Immunology | 2007 |
Proinsulin maturation, misfolding, and proteotoxicity
M Liu, I Hodish, CJ Rhodes, P Arvan |
Proceedings of the National Academy of Sciences | 2007 |
Expression of mutant Ins2C96Y results in enhanced tubule formation causing enlargement of pre-Golgi intermediates of CHO cells
JY Fan, J Roth, C Zuber |
Histochemistry and Cell Biology | 2007 |
Dominant-negative effects of a novel mutated Ins2 allele causes early-onset diabetes and severe beta-cell loss in Munich Ins2C95S mutant mice
N Herbach, B Rathkolb, E Kemter, L Pichl, M Klaften, MH de Angelis, PA Halban, E Wolf, B Aigner, R Wanke |
Diabetes | 2007 |
Endoplasmic Reticulum Stress Signaling in Pancreaticβ-Cells
SG Fonseca, KL Lipson, F Urano |
Antioxidants & Redox Signaling | 2007 |
Dimorphic gene expression patterns of anorexigenic and orexigenic peptides in hypothalamus account male and female hyperphagia in Akita type 1 diabetic mice
M Toyoshima, A Asakawa, M Fujimiya, K Inoue, S Inoue, M Kinboshi, A Koizumi |
Biochemical and Biophysical Research Communications | 2007 |
Endoplasmic Reticulum Stress Signaling in Pancreatic β -Cells
SG Fonseca, KL Lipson, F Urano |
Antioxidants & Redox Signaling | 2007 |
Diabetic modifier QTLs identified in F2 intercrosses between Akita and A/J mice
S Takeshita, M Moritani, K Kunika, H Inoue, M Itakura |
Mammalian Genome | 2006 |
Endoplasmic Reticulum Stress Increases Glucose-6-Phosphatase and Glucose Cycling in Liver Cells
D Wang, Y Wei, D Schmoll, KN Maclean, MJ Pagliassotti |
Endocrinology | 2006 |
Proinsulin lacking the A7-B7 disulfide bond, Ins2Akita, tends to aggregate due to the exposed hydrophobic surface
T Yoshinaga, K Nakatome, J Nozaki, M Naitoh, J Hoseki, H Kubota, K Nagata, A Koizumi |
Biological Chemistry | 2005 |
Roles of CHOP/GADD153 in endoplasmic reticulum stress
S Oyadomari, M Mori |
Cell Death and Differentiation | 2004 |
Misfolded proinsulin accumulates in expanded pre‐Golgi intermediates and endoplasmic reticulum subdomains in pancreatic beta cells of Akita mice
C Zuber, JY Fan, B Guhl, J Roth |
The FASEB Journal | 2004 |
High ER stress in β-cells stimulates intracellular degradation of misfolded insulin
JR Allen, LX Nguyen, KE Sargent, KL Lipson, A Hackett, F Urano |
Biochemical and Biophysical Research Communications | 2004 |
Genetic Dissection of the Familial Cerebral Arteriovenous Malformation
K Takenaka, J Moroi, S Yamada, H Yamakawa, M Abe, K Tabuchi, A Koizumi |
Japanese Journal of Neurosurgery | 2004 |
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AY Savinov, FS Wong, AC Stonebraker, AV Chervonsky |
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Presentation of Antigen by Endothelial Cells and Chemoattraction Are Required for Homing of Insulin-specific CD8 + T Cells
AY Savinov, FS Wong, AC Stonebraker, AV Chervonsky |
Journal of Experimental Medicine | 2003 |
Impact of Endoplasmic Reticulum Stress Pathway on Pancreatic β-Cells and Diabetes Mellitus
E Araki, S Oyadomari, M Mori |
Experimental biology and medicine (Maywood, N.J.) | 2003 |
Targeted disruption of the CHOP gene delays the onset of endoplasmic reticulum stress-mediated diabetes in Akita mice
Seiichi Oyadomari, Akio Koizumi, Kiyoshi Takeda, Tomomi Gotoh, Shizuo Akira, Eiichi Araki, Masataka Mori |
Journal of Clinical Investigation | 2002 |
Increase in Oxidative Stress in Kidneys of Diabetic Akita Mice
Y UENO, F HORIO, K UCHIDA, M NAITO, H NOMURA, Y KATO, T TSUDA, S TOYOKUNI, T OSAWA |
Bioscience, Biotechnology, and Biochemistry | 2002 |
Complications of IgA Nephropathy in a Non-Insulin-Dependent Diabetes Model, the Akita Mouse
T Haseyama, T Fujita, F Hirasawa, M Tsukada, H Wakui, A Komatsuda, H Ohtani, AB Miura, H Imai, A Koizumi |
The Tohoku Journal of Experimental Medicine | 2002 |
New mouse model to study islet transplantation in insulin-dependent diabetes mellitus:
CE Mathews, SH Langley, EH Leiter |
Transplantation | 2002 |
Developing a New Model for Non-Insulin Dependent Diabetes Mellitus (NIDDM) by Using the Philippine Wild Mouse, Mus musculus castaneus
RV ANUNCIADO, T IMAMURA, T OHNO, F HORIO, T NAMIKAWA |
Experimental Animals | 2000 |
A mutation in the insulin 2 gene induces diabetes with severe pancreatic β-cell dysfunction in the Mody mouse
J Wang, T Takeuchi, S Tanaka, SK Kubo, T Kayo, D Lu, K Takata, A Koizumi, T Izumi |
Journal of Clinical Investigation | 1999 |