Copeptin under glucagon stimulation
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ORIGINAL ARTICLE
Copeptin under glucagon stimulation Krzysztof C. Lewandowski1 • Andrzej Lewin´ski1 • El_zbieta Skowron´ska-Jo´z´wiak1 Magdalena Stasiak2 • Wojciech Horzelski3 • Georg Brabant4,5
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Received: 8 August 2015 / Accepted: 20 October 2015 / Published online: 17 November 2015 Ó The Author(s) 2015. This article is published with open access at Springerlink.com
Abstract Stimulation of growth hormone (GH) and adrenocorticotropic hormone (ACTH) secretion by glucagon is a standard procedure to assess pituitary dysfunction but the pathomechanism of glucagon action remains unclear. As arginine vasopressin (AVP) may act on the release of both, GH and ACTH, we tested here the role of AVP in GST by measuring a stable precursor fragment, copeptin, which is stoichiometrically secreted with AVP in a 1:1 ratio. ACTH, cortisol, GH, and copeptin were measured at 0, 60, 90, 120, 150, and 180 min during GST in 79 subjects: healthy controls (Group 1, n = 32), subjects with pituitary disease, but with adequate cortisol and GH responses during GST (Group 2, n = 29), and those with overt hypopituitarism (Group 3, n = 18). Copeptin concentrations significantly increased over baseline 150 and 180 min following glucagon stimulation in controls and Electronic supplementary material The online version of this article (doi:10.1007/s12020-015-0783-7) contains supplementary material, which is available to authorized users. & Georg Brabant [email protected] 1
Department of Endocrinology and Metabolic Diseases, Medical University of Lodz, Lodz, Poland
2
Department of Endocrinology and Metabolic Diseases, Polish Mother’s Memorial Hospital - Research Institute, Lodz, Poland
3
Faculty of Mathematics and Computer Science, University of Lodz, Lodz, Poland
4
Experimental and Clinical Endocrinology Med Clinic I, University of Luebeck, Ratzeburger Allee 160, 23538 Lu¨beck, Germany
5
Department of Endocrinology, The Christie Manchester Academic Health Science Centre, Wilmslow Rd, Manchester M20 4BX, UK
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patients with intact pituitary function but not in hypopituitarism. Copeptin concentrations were stimulated over time and the maximal increment correlated with ACTH, while correlations between copeptin and GH were weaker. Interestingly, copeptin as well as GH secretion was significantly attenuated when comparing subjects within the highest to those in the lowest BMI quartile (p \ 0.05). Copeptin is significantly released following glucagon stimulation. As this release is BMI-dependent, the timedependent relation between copeptin and GH may be obscured, whereas the close relation to ACTH suggests that AVP/copeptin release might be linked to the activation of the adrenal axis. Keywords Copeptin Glucagon stimulation test Hypopituitarism GH ACTH Cortisol
Introduction Copeptin is a 39-amino-acids containing glycosylated peptide, derived from the C-terminal part of the AVP precursor [1]. In the process of proteolysis, the AVP precursor is processed to AVP, neurophysin II, and copeptin in equimolar amounts. Plasma
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