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Horm Metab Res 2017; 49(01): 43-49
DOI: 10.1055/s-0042-116157
Endocrine Research
© Georg Thieme Verlag KG Stuttgart · New York

Elevated Steroid Hormone Production in the db/db Mouse Model of Obesity and Type 2 Diabetes

Authors

  • Anja Hofmann

    1   Division of Vascular Endothelium and Microcirculation, Department of Medicine III, University Hospital Carl Gustav Carus Dresden, Technische Universität Dresden, Dresden, Germany

  • Mirko Peitzsch

    2   Division of Clinical Neurochemistry, Institute of Clinical Chemistry and Laboratory Medicine, University Hospital Carl Gustav Carus Dresden, Technische Universität Dresden, Dresden, Germany

  • Coy Brunssen

    1   Division of Vascular Endothelium and Microcirculation, Department of Medicine III, University Hospital Carl Gustav Carus Dresden, Technische Universität Dresden, Dresden, Germany

  • Jennifer Mittag

    1   Division of Vascular Endothelium and Microcirculation, Department of Medicine III, University Hospital Carl Gustav Carus Dresden, Technische Universität Dresden, Dresden, Germany

  • Annett Jannasch

    3   Department of Cardiac Surgery, Herzzentrum Dresden, Medical Faculty Carl Gustav Carus Dresden, Technische Universität Dresden, Dresden, Germany

  • Annika Frenzel

    1   Division of Vascular Endothelium and Microcirculation, Department of Medicine III, University Hospital Carl Gustav Carus Dresden, Technische Universität Dresden, Dresden, Germany

  • Nicholas Brown

    4   Cardio Metabolic Diseases, Boehringer Ingelheim Pharmaceuticals Inc., Ridgefield, CT, USA

  • Steven M. Weldon

    4   Cardio Metabolic Diseases, Boehringer Ingelheim Pharmaceuticals Inc., Ridgefield, CT, USA

  • Graeme Eisenhofer

    2   Division of Clinical Neurochemistry, Institute of Clinical Chemistry and Laboratory Medicine, University Hospital Carl Gustav Carus Dresden, Technische Universität Dresden, Dresden, Germany
    5   Department of Medicine III, University Hospital Carl Gustav Carus Dresden, Technische Universität Dresden, Dresden, Germany

  • Stefan R. Bornstein

    5   Department of Medicine III, University Hospital Carl Gustav Carus Dresden, Technische Universität Dresden, Dresden, Germany
    6   Endocrinology and Diabetes, Division of Diabetes & Nutritional Sciences, Rayne Institute, Denmark Hill Campus, Faculty of Life Sciences & Medicine, Kings College London, London, UK

  • Henning Morawietz

    1   Division of Vascular Endothelium and Microcirculation, Department of Medicine III, University Hospital Carl Gustav Carus Dresden, Technische Universität Dresden, Dresden, Germany
    5   Department of Medicine III, University Hospital Carl Gustav Carus Dresden, Technische Universität Dresden, Dresden, Germany
Further Information

Publication History

received 04 May 2016

accepted 23 August 2016

Publication Date:
03 November 2016 (online)

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Abstract

Obesity and type 2 diabetes have become a major public health problem worldwide. Steroid hormone dysfunction appears to be linked to development of obesity and type 2 diabetes and correction of steroid abnormalities may offer new approaches to therapy. We therefore analyzed plasma steroids in 15–16 week old obese and diabetic db/db mice using liquid chromatography-tandem mass spectrometry. Lean db/+ served as controls. Db/db mice developed obesity, hyperglycemia, hyperleptinemia, and hyperlipidemia. Hepatic triglyceride storage was increased and adiponectin and pancreatic insulin were lowered. Aldosterone, corticosterone, 11-deoxycorticosterone, and progesterone were respectively increased by 3.6-, 2.9-, 3.4, and 1.7-fold in db/db mice compared to controls. Ratios of aldosterone-to-progesterone and corticosterone-to-progesterone were respectively 2.0- and 1.5-fold higher in db/db mice. Genes associated with steroidogenesis were quantified in the adrenal glands and gonadal adipose tissues. In adrenals, Cyp11b2, Cyp11b1, Cyp21a1, Hsd3b1, Cyp11a1, and StAR were all significantly increased in db/db mice compared with db/+ controls. In adipose tissue, no Cyp11b2 or Cyp11b1 transcripts were detected and no differences in Cyp21a1, Hsd3b1, Cyp11a1, or StAR expression were found between db/+ and db/db mice. In conclusion, the present study showed an elevated steroid hormone production and adrenal steroidogenesis in the db/db model of obesity and type 2 diabetes.

Key words

aldosterone - diabetes mellitus type 2 - glucocorticoids - obesity - steroid hormones

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