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Exploring the role of the metabolite-sensing receptor GPR109a in diabetic nephropathy.
Snelson, Matthew; Tan, Sih Min; Higgins, Gavin C; Lindblom, Runa S J; Coughlan, Melinda T.
Afiliación
  • Snelson M; Department of Diabetes, Central Clinical School, Alfred Medical Research and Education Precinct, Monash University, Melbourne, Victoria, Australia.
  • Tan SM; Department of Diabetes, Central Clinical School, Alfred Medical Research and Education Precinct, Monash University, Melbourne, Victoria, Australia.
  • Higgins GC; Department of Diabetes, Central Clinical School, Alfred Medical Research and Education Precinct, Monash University, Melbourne, Victoria, Australia.
  • Lindblom RSJ; Department of Diabetes, Central Clinical School, Alfred Medical Research and Education Precinct, Monash University, Melbourne, Victoria, Australia.
  • Coughlan MT; Department of Diabetes, Central Clinical School, Alfred Medical Research and Education Precinct, Monash University, Melbourne, Victoria, Australia.
Am J Physiol Renal Physiol ; 318(3): F835-F842, 2020 03 01.
Article en En | MEDLINE | ID: mdl-32068460
Alterations in gut homeostasis may contribute to the progression of diabetic nephropathy. There has been recent attention on the renoprotective effects of metabolite-sensing receptors in chronic renal injury, including the G protein-coupled receptor (GPR)109a, which ligates the short-chain fatty acid butyrate. However, the role of GPR109a in the development of diabetic nephropathy, a milieu of diminished microbiome-derived metabolites, has not yet been determined. The present study aimed to assess the effects of insufficient GPR109a signaling, via genetic deletion of GPR109a, on the development of renal injury in diabetic nephropathy. Gpr109a-/- mice or their wild-type littermates (Gpr109a+/+) were rendered diabetic with streptozotocin. Mice received a control diet or an isocaloric high-fiber diet (12.5% resistant starch) for 24 wk, and gastrointestinal permeability and renal injury were determined. Diabetes was associated with increased albuminuria, glomerulosclerosis, and inflammation. In comparison, Gpr109a-/- mice with diabetes did not show an altered renal phenotype. Resistant starch supplementation did not afford protection from renal injury in diabetic nephropathy. While diabetes was associated with alterations in intestinal morphology, intestinal permeability assessed in vivo using the FITC-dextran test was unaltered. GPR109a deletion did not worsen gastrointestinal permeability. Furthermore, 12.5% resistant starch supplementation, at physiological concentrations, had no effect on intestinal permeability or morphology. The results of this study indicate that GPR109a does not play a critical role in intestinal homeostasis in a model of type 1 diabetes or in the development of diabetic nephropathy.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Receptores Acoplados a Proteínas G / Nefropatías Diabéticas Límite: Animals Idioma: En Revista: Am J Physiol Renal Physiol Asunto de la revista: FISIOLOGIA / NEFROLOGIA Año: 2020 Tipo del documento: Article País de afiliación: Australia Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Receptores Acoplados a Proteínas G / Nefropatías Diabéticas Límite: Animals Idioma: En Revista: Am J Physiol Renal Physiol Asunto de la revista: FISIOLOGIA / NEFROLOGIA Año: 2020 Tipo del documento: Article País de afiliación: Australia Pais de publicación: Estados Unidos