In vivo effect of glucose-dependent insulinotropic peptide (GIP) on the gene expression of calcitonin peptides in human subcutaneous adipose tissue Olga Pivovarova a, b, ⁎, Özlem Gögebakan a, b , Martin A. Osterhoff a, b , Michael Nauck c , Andreas F.H. Pfeiffer a, b , Natalia Rudovich a, b a Department of Clinical Nutrition, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany b Department Endocrinology, Diabetes and Nutrition, Charité University Medicine, Campus Benjamin Franklin, Berlin, Germany c Diabetes Centre Bad Lauterberg, Bad Lauterberg, Germany abstract article info Article history: Received 9 March 2012 Received in revised form 25 June 2012 Accepted 27 August 2012 Available online 5 September 2012 Keywords: Glucose-dependent insulinotropic peptide Calcitonin gene-related peptide‐I Procalcitonin Human subcutaneous adipose tissue Background: Increased plasma levels of calcitonin gene-related peptide‐I (CGRP-I) and procalcitonin (Pro-CT) (both also named calcitonin peptides (CT peptides)) are associated with obesity and systemic inflammation. Glucose-dependent insulinotropic polypeptide (GIP), a nutrient-dependent incretin hormone, was recently found to induce CGRP-I and CT expression in human adipocytes in vitro. However, a physiological relevance of a possible interaction between GIP and CT peptides has not yet been studied. Methods: In this study, we analyzed the effect of GIP on the expression of CGRP-I and CT mRNA in human sub- cutaneous adipose tissue within a randomized, controlled trial. Seventeen male obese subjects were infused with GIP [2.0 pmol kg -1 min -1 for 240 min] or placebo, either in the fasting state, during euglycemic– hyperinsulinemic (EC) or hyperglycemic–hyperinsulinemic clamps (HC). Results: The CGRP-I gene expression was detected in all investigated adipose tissue samples, whereas very low CT expression was found in only 8 out of 116 analyzed samples. No significant influence of either GIP or glucose and insulin infusions on the CGRP-I and CT expression was observed in any of the individual exper- iments (GIP infusion, EC and HC) or in the combined analysis of all experiments with and without GIP. Furthermore, CGRP-I expression was not correlated with plasma GIP level before or after 240 min of infusions or clamps. Conclusion: In contrast to in vitro data, an acute application of GIP has no effect on mRNA expression of CT peptides in subcutaneous adipose tissue of obese humans. © 2012 Elsevier B.V. All rights reserved. 1. Introduction Inflammatory signals originating from adipose tissue are estab- lished components in the development of insulin resistance and subse- quent diseases such as type 2 diabetes and atherosclerosis [1]. In this context, overnutrition is considered as a cause of obesity which stimu- lates secretion of different cytokines and inflammatory molecules from the adipose tissue into the circulation. Recently published data from Timper et al. [2] suggests that the intestinal incretin hormone, glucose-dependent insulinotropic peptide (GIP) released in response to glucose or fat consumption directly stimulates expression of calcitonin (CT) peptides in human adipocytes in vitro. Authors put forward an elegant hypothesis representing an early meal-dependent hormonal signal inducing the expression and secretion of these pro- inflammatory peptides from adipose tissue. GIP is a gastrointestinal hormone demonstrating multiple effects in the range of target tissues including adipose tissue [3]. In adipocytes, GIP directly influences cell differentiation as well as glucose and lipid metabolism [3–5]. Central obesity is associated with elevated GIP plas- ma levels in humans [3]. Moreover, inhibition of GIP signaling prevents diet-induced obesity in mice [6] and ameliorates glucose intolerance in the fat-induced diabesity [7]. CT-peptides (calcitonin gene-related peptide‐I (CGRP-I) and procalcitonin (Pro-CT)) are products of alternative splicing of CALC-I gene pre-mRNA [8] expressed in various human tissues [9]. Elevated circulating concentrations of CT-peptides are established markers of sepsis, sepsis-like conditions and systemic inflammation [10–12]. Moreover, CT-peptides are suggested as novel adipose tissue secretion factors exerting autocrine/paracrine roles [8]. The increased CGRP-I and CT expression were observed in adipose tissue of sepsis patients as well as of morbid obese subjects and was little to no detectable in the adipose tissue of healthy non obese sub- jects [2,8,13,14]. Circulating levels of both peptides were positively correlated with markers of insulin resistance and central obesity in large cohort observation studies [15,16]. Regulatory Peptides 179 (2012) 29–32 ⁎ Corresponding author at: German Institute of Human Nutrition Potsdam, Arthur- Scheunert-Allee 114‐116, 14558 Nuthetal, Germany. Tel.: +49 33 2008 82749; fax: +49 33 2008 82777. E-mail address: olga.pivovarova@dife.de (O. Pivovarova). 0167-0115/$ – see front matter © 2012 Elsevier B.V. All rights reserved. http://dx.doi.org/10.1016/j.regpep.2012.08.004 Contents lists available at SciVerse ScienceDirect Regulatory Peptides journal homepage: www.elsevier.com/locate/regpep