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Type 2 diabetes susceptibility genes on mouse chromosome 11 under high sucrose environment.
Kobayashi, Misato; Ueda, Hironori; Babaya, Naru; Itoi-Babaya, Michiko; Noso, Shinsuke; Fujisawa, Tomomi; Horio, Fumihiko; Ikegami, Hiroshi.
Afiliación
  • Kobayashi M; Department of Geriatric Medicine, Osaka University Graduate School of Medicine, Osaka, Japan.
  • Ueda H; Department of Animal Sciences, Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya, Japan.
  • Babaya N; Department of Molecular Endocrinology, Osaka University Graduate School of Medicine, Osaka, Japan.
  • Itoi-Babaya M; Health Care Center, KSC branch, Kwansei Gakuin University, Sanda, Hyogo, Japan.
  • Noso S; Department of Endocrinology, Metabolism and Diabetes, Kindai University Faculty of Medicine, 337-2 Ohno-higashi, Osaka-sayama, Osaka, 589-8511, Japan.
  • Fujisawa T; Department of Geriatric Medicine, Osaka University Graduate School of Medicine, Osaka, Japan.
  • Horio F; Health Care Center, Rinku General Medical Center, Osaka, Japan.
  • Ikegami H; Department of Endocrinology, Metabolism and Diabetes, Kindai University Faculty of Medicine, 337-2 Ohno-higashi, Osaka-sayama, Osaka, 589-8511, Japan.
BMC Genet ; 21(1): 81, 2020 07 23.
Article en En | MEDLINE | ID: mdl-32703163
BACKGROUND: Both genetic and environmental factors contribute to type 2 diabetes development. We used consomic mice established from an animal type 2 diabetes model to identify susceptibility genes that contribute to type 2 diabetes development under specific environments. We previously established consomic strains (C3H-Chr 11NSY and C3H-Chr 14NSY) that possess diabetogenic Chr 11 or 14 of the Nagoya-Shibata-Yasuda (NSY) mouse, an animal model of spontaneous type 2 diabetes, in the genetic background of C3H mice. To search genes contribute to type 2 diabetes under specific environment, we first investigated whether sucrose administration deteriorates type 2 diabetes-related traits in the consomic strains. We dissected loci on Chr 11 by establishing congenic strains possessing different segments of NSY-derived Chr 11 under sucrose administration. RESULTS: In C3H-Chr 11NSY mice, sucrose administration for 10 weeks deteriorated hyperglycemia, insulin resistance, and impaired insulin secretion, which is comparable to NSY mice with sucrose. In C3H-Chr 14NSY mice, sucrose administration induced glucose intolerance, but not insulin resistance and impaired insulin secretion. To dissect the gene(s) existing on Chr 11 for sucrose-induced type 2 diabetes, we constructed four novel congenic strains (R1, R2, R3, and R4) with different segments of NSY-derived Chr 11 in C3H mice. R2 mice showed marked glucose intolerance and impaired insulin secretion comparable to C3H-Chr 11NSY mice. R3 and R4 mice also showed impaired insulin secretion. R4 mice showed significant decreases in white adipose tissue, which is in the opposite direction from parental C3H-Chr 11NSY and NSY mice. None of the four congenic strains showed insulin resistance. CONCLUSIONS: Genes on mouse Chr 11 could explain glucose intolerance, impaired insulin secretion, insulin resistance in NSY mice under sucrose administration. Congenic mapping with high sucrose environment localized susceptibility genes for type 2 diabetes associated with impaired insulin secretion in the middle segment (26.0-63.4 Mb) of Chr 11. Gene(s) that decrease white adipose tissue were mapped to the distal segment of Chr 11. The identification of diabetogenic gene on Chr 11 in the future study will facilitate precision medicine in type 2 diabetes by controlling specific environments in targeted subjects with susceptible genotypes.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Sacarosa / Predisposición Genética a la Enfermedad / Diabetes Mellitus Tipo 2 Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: BMC Genet Asunto de la revista: BIOLOGIA MOLECULAR / BIOTECNOLOGIA Año: 2020 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Reino Unido

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Sacarosa / Predisposición Genética a la Enfermedad / Diabetes Mellitus Tipo 2 Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: BMC Genet Asunto de la revista: BIOLOGIA MOLECULAR / BIOTECNOLOGIA Año: 2020 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Reino Unido