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Skeletal muscle overexpression of sAnk1.5 in transgenic mice does not predispose to type 2 diabetes.
Pierantozzi, E; Raucci, L; Buonocore, S; Rubino, E M; Ding, Q; Laurino, A; Fiore, F; Soldaini, M; Chen, J; Rossi, D; Vangheluwe, P; Chen, H; Sorrentino, V.
Afiliação
  • Pierantozzi E; Department of Molecular and Developmental Medicine, University of Siena, 53100, Siena, Italy.
  • Raucci L; Department of Molecular and Developmental Medicine, University of Siena, 53100, Siena, Italy.
  • Buonocore S; Department of Molecular and Developmental Medicine, University of Siena, 53100, Siena, Italy.
  • Rubino EM; Department of Molecular and Developmental Medicine, University of Siena, 53100, Siena, Italy.
  • Ding Q; Department of Cardio-Thoracic Surgery, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing, 210008, Jiangsu, China.
  • Laurino A; Department of Molecular and Developmental Medicine, University of Siena, 53100, Siena, Italy.
  • Fiore F; Department of Molecular and Developmental Medicine, University of Siena, 53100, Siena, Italy.
  • Soldaini M; Department of Molecular and Developmental Medicine, University of Siena, 53100, Siena, Italy.
  • Chen J; Laboratory of Cellular Transport Systems, Department of Cellular and Molecular Medicine, Katholieke Universiteit Leuven (KU Leuven), 3000, Leuven, Belgium.
  • Rossi D; Department of Molecular and Developmental Medicine, University of Siena, 53100, Siena, Italy.
  • Vangheluwe P; Interdepartmental Program of Molecular Diagnosis and Pathogenetic Mechanisms of Rare Genetic Diseases, Azienda Ospedaliera Universitaria Senese, 53100, Siena, Italy.
  • Chen H; Laboratory of Cellular Transport Systems, Department of Cellular and Molecular Medicine, Katholieke Universiteit Leuven (KU Leuven), 3000, Leuven, Belgium.
  • Sorrentino V; Department of Cardio-Thoracic Surgery, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing, 210008, Jiangsu, China.
Sci Rep ; 13(1): 8195, 2023 05 20.
Article em En | MEDLINE | ID: mdl-37210436
ABSTRACT
Genome-wide association studies (GWAS) and cis-expression quantitative trait locus (cis-eQTL) analyses indicated an association of the rs508419 single nucleotide polymorphism (SNP) with type 2 diabetes (T2D). rs508419 is localized in the muscle-specific internal promoter (P2) of the ANK1 gene, which drives the expression of the sAnk1.5 isoform. Functional studies showed that the rs508419 C/C variant results in increased transcriptional activity of the P2 promoter, leading to higher levels of sAnk1.5 mRNA and protein in skeletal muscle biopsies of individuals carrying the C/C genotype. To investigate whether sAnk1.5 overexpression in skeletal muscle might predispose to T2D development, we generated transgenic mice (TgsAnk1.5/+) in which the sAnk1.5 coding sequence was selectively overexpressed in skeletal muscle tissue. TgsAnk1.5/+ mice expressed up to 50% as much sAnk1.5 protein as wild-type (WT) muscles, mirroring the difference reported between individuals with the C/C or T/T genotype at rs508419. However, fasting glucose levels, glucose tolerance, insulin levels and insulin response in TgsAnk1.5/+ mice did not differ from those of age-matched WT mice monitored over a 12-month period. Even when fed a high-fat diet, TgsAnk1.5/+ mice only presented increased caloric intake, but glucose disposal, insulin tolerance and weight gain were comparable to those of WT mice fed a similar diet. Altogether, these data indicate that sAnk1.5 overexpression in skeletal muscle does not predispose mice to T2D susceptibility.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Resistência à Insulina / Diabetes Mellitus Tipo 2 Limite: Animals Idioma: En Revista: Sci Rep Ano de publicação: 2023 Tipo de documento: Article País de afiliação: Itália

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Resistência à Insulina / Diabetes Mellitus Tipo 2 Limite: Animals Idioma: En Revista: Sci Rep Ano de publicação: 2023 Tipo de documento: Article País de afiliação: Itália