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Alpha Cell Thioredoxin-interacting Protein Deletion Improves Diabetes-associated Hyperglycemia and Hyperglucagonemia.
Lu, Brian; Chen, Junqin; Xu, Guanlan; Grayson, Truman B; Jing, Gu; Jo, SeongHo; Shalev, Anath.
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  • Lu B; Comprehensive Diabetes Center and Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL.
  • Chen J; Comprehensive Diabetes Center and Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL.
  • Xu G; Comprehensive Diabetes Center and Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL.
  • Grayson TB; Comprehensive Diabetes Center and Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL.
  • Jing G; Comprehensive Diabetes Center and Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL.
  • Jo S; Comprehensive Diabetes Center and Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL.
  • Shalev A; Comprehensive Diabetes Center and Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL.
Endocrinology ; 163(11)2022 10 11.
Article en En | MEDLINE | ID: mdl-35957590
Thioredoxin-interacting protein (TXNIP) has emerged as a key factor in pancreatic beta cell biology, and its upregulation by glucose and diabetes contributes to the impairment in functional beta cell mass and glucose homeostasis. In addition, beta cell deletion of TXNIP protects against diabetes in different mouse models. However, while TXNIP is ubiquitously expressed, its role in pancreatic alpha cells has remained elusive. We generated an alpha cell TXNIP knockout (aTKO) mouse and assessed the effects on glucose homeostasis. While no significant changes were observed on regular chow, after a 30-week high-fat diet, aTKO animals showed improvement in glucose tolerance and lower blood glucose levels compared to their control littermates. Moreover, in the context of streptozotocin (STZ)-induced diabetes, aTKO mice showed significantly lower blood glucose levels compared to controls. While serum insulin levels were reduced in both control and aTKO mice, STZ-induced diabetes significantly increased glucagon levels in control mice, but this effect was blunted in aTKO mice. Moreover, glucagon secretion from aTKO islets was >2-fold lower than from control islets, while insulin secretion was unchanged in aTKO islets. At the same time, no change in alpha cell or beta cell numbers or mass was observed, and glucagon and insulin expression and content were comparable in isolated islets from aTKO and control mice. Thus together the current studies suggest that downregulation of alpha cell TXNIP is associated with reduced glucagon secretion and that this may contribute to the glucose-lowering effects observed in diabetic aTKO mice.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Enfermedades Pancreáticas / Diabetes Mellitus Experimental / Células Secretoras de Glucagón / Células Secretoras de Insulina / Hiperglucemia Tipo de estudio: Prognostic_studies / Risk_factors_studies Límite: Animals Idioma: En Revista: Endocrinology Año: 2022 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Enfermedades Pancreáticas / Diabetes Mellitus Experimental / Células Secretoras de Glucagón / Células Secretoras de Insulina / Hiperglucemia Tipo de estudio: Prognostic_studies / Risk_factors_studies Límite: Animals Idioma: En Revista: Endocrinology Año: 2022 Tipo del documento: Article Pais de publicación: Estados Unidos