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Deoxysphingolipids: Atypical Skeletal Muscle Lipids Related to Insulin Resistance in Humans That Decrease Insulin Sensitivity In Vitro.
Zarini, Simona; Zemski Berry, Karin A; Kahn, Darcy E; Garfield, Amanda; Perreault, Leigh; Kerege, Anna; Bergman, Bryan C.
Afiliação
  • Zarini S; Division of Endocrinology, Metabolism, and Diabetes, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO.
  • Zemski Berry KA; Division of Endocrinology, Metabolism, and Diabetes, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO.
  • Kahn DE; Division of Endocrinology, Metabolism, and Diabetes, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO.
  • Garfield A; Division of Endocrinology, Metabolism, and Diabetes, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO.
  • Perreault L; Division of Endocrinology, Metabolism, and Diabetes, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO.
  • Kerege A; Division of Endocrinology, Metabolism, and Diabetes, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO.
Diabetes ; 72(7): 884-897, 2023 07 01.
Article em En | MEDLINE | ID: mdl-37186949
Sphingolipids are thought to promote skeletal muscle insulin resistance. Deoxysphingolipids (dSLs) are atypical sphingolipids that are increased in the plasma of individuals with type 2 diabetes and cause ß-cell dysfunction in vitro. However, their role in human skeletal muscle is unknown. We found that dSL species are significantly elevated in muscle of individuals with obesity and type 2 diabetes compared with athletes and lean individuals and are inversely related to insulin sensitivity. Furthermore, we observed a significant reduction in muscle dSL content in individuals with obesity who completed a combined weight loss and exercise intervention. Increased dSL content in primary human myotubes caused a decrease in insulin sensitivity associated with increased inflammation, decreased AMPK phosphorylation, and altered insulin signaling. Our findings reveal a central role for dSL in human muscle insulin resistance and suggest dSLs as therapeutic targets for the treatment and prevention of type 2 diabetes. ARTICLE HIGHLIGHTS: Deoxysphingolipids (dSLs) are atypical sphingolipids elevated in the plasma of individuals with type 2 diabetes, and their role in muscle insulin resistance has not been investigated. We evaluated dSL in vivo in skeletal muscle from cross-sectional and longitudinal insulin-sensitizing intervention studies and in vitro in myotubes manipulated to synthesize higher dSLs. dSLs were increased in the muscle of people with insulin resistance, inversely correlated to insulin sensitivity, and significantly decreased after an insulin-sensitizing intervention; increased intracellular dSL concentrations cause myotubes to become more insulin resistant. Reduction of muscle dSL levels is a potential novel therapeutic target to prevent/treat skeletal muscle insulin resistance.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Resistência à Insulina / Diabetes Mellitus Tipo 2 Tipo de estudo: Diagnostic_studies / Observational_studies / Prevalence_studies / Risk_factors_studies Limite: Humans Idioma: En Revista: Diabetes Ano de publicação: 2023 Tipo de documento: Article País de publicação: Estados Unidos
Texto completo
Adicionar na Minha BVS
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Resistência à Insulina / Diabetes Mellitus Tipo 2 Tipo de estudo: Diagnostic_studies / Observational_studies / Prevalence_studies / Risk_factors_studies Limite: Humans Idioma: En Revista: Diabetes Ano de publicação: 2023 Tipo de documento: Article País de publicação: Estados Unidos