Differences in associations between HSD11B1 gene expression and metabolic parameters in subjects with and without impaired glucose homeostasis C. Karlsson a,b, *, M. Jerna ˚s a , B. Olsson a , T. Lystig a,b , A. Gummesson a,b , L. Storlien c , L. Groop d,e , B. Carlsson a,b a Department of Molecular and Clinical Medicine, The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden b AstraZeneca R&D, Mo ¨ lndal, Sweden c Institute of Obesity, Nutrition & Exercise, University of Sydney, Australia d Department of Clinical Sciences, Diabetes and Endocrinology Research Unit and Lund University Diabetes Center, CRC, Malmo ¨ University Hospital, Lund University, Malmo ¨, Sweden e Programme in Molecular Medicine, Helsinki University, Helsinki, Finland 1. Introduction In rodents, the role of 11b-hydroxysteroid dehydrogenase type 1 (HSD11B1) in the development of obesity and features of the metabolic syndrome is well established [1–6]. In humans, it is well known that glucocorticoid excess leads to the development of visceral obesity and other features of the metabolic syndrome [7–9]. However, circulating diabetes research and clinical practice xxx (2010) xxx–xxx article info Article history: Received 17 December 2009 Received in revised form 3 March 2010 Accepted 8 March 2010 Keywords: HSD11B1 Metabolic syndrome Type 2 diabetes abstract Aims: Animal studies indicate a role for 11b-hydroxysteroid dehydrogenase type 1 (HSD11B1) in the development of obesity. The association to glucose homeostasis is less clear. We investigated the relationship between HSD11B1 mRNA levels in adipose tissue and in skeletal muscle and anthropometric and metabolic measurements in humans with and without impaired glucose homeostasis. Methods: Twelve obese subjects with impaired glucose homeostasis (MetS+) and 12 obese controls (MetSÀ) received a Very Low Calorie Diet for 16 weeks and adipose tissue biopsies, blood samples and measurements were obtained. In a second cohort, skeletal muscle biopsies, blood samples and measurements were obtained from 18 subjects with type 2 diabetes (T2DM) and 17 subjects with normal glucose tolerance (NGT). Gene expression was measured by DNA microarray in both studies. Results: HSD11B1 mRNA levels were reduced during diet, and anthropometric measure- ments and metabolic parameters were associated with HSD11B1 mRNA levels in the MetSÀ group. However, in the MetS+ group these associations were lost or in opposite direction. This difference was also observed in skeletal muscle between T2DM and NGT. Conclusions: HSD11B1 mRNA levels are associated with metabolic parameters and anthro- pometric measurements in subjects with normal glucose homeostasis but not in subjects with impaired glucose homeostasis. # 2010 Elsevier Ireland Ltd. All rights reserved. * Corresponding author at: Department of Molecular and Clinical Medicine, The Sahlgrenska Academy at University of Gothenburg, Vita stra ˚ ket 15, SE-413 45 Gothenburg, Sweden. Tel.: +46 31 706 41 03/46 708 46 74 13; fax: +46 31 776 38 44. E-mail addresses: cecilia.karlsson@astrazeneca.com, cecilia-karlsson@hotmail.com (C. Karlsson). DIAB-4750; No. of Pages 7 Please cite this article in press as: C. Karlsson et al., Differences in associations between HSD11B1 gene expression and metabolic parameters in subjects with and without impaired glucose homeostasis, Diab. Res. Clin. Pract. (2010), doi:10.1016/j.diabres.2010.03.009 Contents lists available at ScienceDirect Diabetes Research and Clinical Practice journal homepage: www.elsevier.com/locate/diabres 0168-8227/$ – see front matter # 2010 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.diabres.2010.03.009