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Pancreatic fat cells of humans with type 2 diabetes display reduced adipogenic and lipolytic activity.
Barroso Oquendo, Morgana; Siegel-Axel, Dorothea; Gerst, Felicia; Lorza-Gil, Estela; Moller, Anja; Wagner, Robert; Machann, Jürgen; Fend, Falko; Königsrainer, Alfred; Heni, Martin; Häring, Hans-Ulrich; Ullrich, Susanne; Birkenfeld, Andreas L.
Afiliación
  • Barroso Oquendo M; German Center for Diabetes Research (DZD e.V.), Tübingen, Germany.
  • Siegel-Axel D; Division of Endocrinology, Diabetology and Nephrology, Department of Internal Medicine IV, University Hospital of Eberhard-Karls-University Tübingen, Tübingen, Germany.
  • Gerst F; German Center for Diabetes Research (DZD e.V.), Tübingen, Germany.
  • Lorza-Gil E; Division of Endocrinology, Diabetology and Nephrology, Department of Internal Medicine IV, University Hospital of Eberhard-Karls-University Tübingen, Tübingen, Germany.
  • Moller A; German Center for Diabetes Research (DZD e.V.), Tübingen, Germany.
  • Wagner R; Institute for Diabetes Research and Metabolic Diseases, Helmholtz Center Munich, Eberhard-Karls-University of Tübingen, Neuherberg, Germany.
  • Machann J; Division of Endocrinology, Diabetology and Nephrology, Department of Internal Medicine IV, University Hospital of Eberhard-Karls-University Tübingen, Tübingen, Germany.
  • Fend F; German Center for Diabetes Research (DZD e.V.), Tübingen, Germany.
  • Königsrainer A; Institute for Diabetes Research and Metabolic Diseases, Helmholtz Center Munich, Eberhard-Karls-University of Tübingen, Neuherberg, Germany.
  • Heni M; Division of Endocrinology, Diabetology and Nephrology, Department of Internal Medicine IV, University Hospital of Eberhard-Karls-University Tübingen, Tübingen, Germany.
  • Häring HU; German Center for Diabetes Research (DZD e.V.), Tübingen, Germany.
  • Ullrich S; Institute for Diabetes Research and Metabolic Diseases, Helmholtz Center Munich, Eberhard-Karls-University of Tübingen, Neuherberg, Germany.
  • Birkenfeld AL; Division of Endocrinology, Diabetology and Nephrology, Department of Internal Medicine IV, University Hospital of Eberhard-Karls-University Tübingen, Tübingen, Germany.
Am J Physiol Cell Physiol ; 320(6): C1000-C1012, 2021 06 01.
Article en En | MEDLINE | ID: mdl-33788629
Obesity, especially visceral fat accumulation, increases the risk of type 2 diabetes (T2D). The purpose of this study was to investigate the impact of T2D on the pancreatic fat depot. Pancreatic fat pads from 17 partial pancreatectomized patients (PPP) were collected, pancreatic preadipocytes isolated, and in vitro differentiated. Patients were grouped using HbA1c into normal glucose tolerant (NGT), prediabetic (PD), and T2D. Transcriptome profiles of preadipocytes and adipocytes were assessed by RNAseq. Insulin sensitivity was estimated by quantifying AKT phosphorylation on Western blots. Lipogenic capacity was assessed with oil red O staining, lipolytic activity via fatty acid release. Secreted factors were measured using ELISA. Comparative transcriptome analysis of preadipocytes and adipocytes indicates defective upregulation of genes governing adipogenesis (NR1H3), lipogenesis (FASN, SCD, ELOVL6, and FADS1), and lipolysis (LIPE) during differentiation of cells from T2D-PPP. In addition, the ratio of leptin/adiponectin mRNA was higher in T2D than in NGT-PPP. Preadipocytes and adipocytes of NGT-PPP were more insulin sensitive than T2D-PPP cells in regard to AKT phosphorylation. Triglyceride accumulation was similar in NGT and T2D adipocytes. Despite a high expression of the receptors NPR1 and NPR2 in NGT and T2D adipocytes, lipolysis was stimulated by ANP 1.74-fold in NGT cells only. This stimulation was further increased by the PDE5 inhibitor dipyridamole (3.09-fold). Dipyridamole and forskolin increased lipolysis receptor independently 1.88-fold and 1.48-fold, respectively, solely in NGT cells. In conclusion, the metabolic status persistently affects differentiation and lipolysis of pancreatic adipocytes. These alterations could aggravate the development of T2D.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Adipocitos / Diabetes Mellitus Tipo 2 / Adipogénesis / Lipogénesis / Lipólisis Límite: Aged / Aged80 / Female / Humans / Male / Middle aged Idioma: En Revista: Am J Physiol Cell Physiol Asunto de la revista: FISIOLOGIA Año: 2021 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Adipocitos / Diabetes Mellitus Tipo 2 / Adipogénesis / Lipogénesis / Lipólisis Límite: Aged / Aged80 / Female / Humans / Male / Middle aged Idioma: En Revista: Am J Physiol Cell Physiol Asunto de la revista: FISIOLOGIA Año: 2021 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Estados Unidos