PDF herunterladen
Horm Metab Res 2016; 48(09): 589-594
DOI: 10.1055/s-0042-109869
Endocrine Care
© Georg Thieme Verlag KG Stuttgart · New York

Insulin-Like Peptide 5 Interacts with Sex Hormones and Metabolic Parameters in a Gender and Adiposity Dependent Manner in Humans

I. V. Wagner
1   Department of Women and Child Health, Pediatric Endocrinology Unit, Karolinska Institutet, Stockholm, Sweden
2   Center for Pediatric Research Leipzig, Department of Women’s and Child Health, University Hospital for Children & Adolescents, University of Leipzig, Leipzig, Germany
3   Integrated Research and Treatment Center (IFB Adiposity Diseases), University of Leipzig, Leipzig, Germany
,
G. Flehmig
4   Division of Endocrinology, Department of Medicine, University of Leipzig, Leipzig, Germany
,
K. Scheuermann
2   Center for Pediatric Research Leipzig, Department of Women’s and Child Health, University Hospital for Children & Adolescents, University of Leipzig, Leipzig, Germany
,
D. Löffler
2   Center for Pediatric Research Leipzig, Department of Women’s and Child Health, University Hospital for Children & Adolescents, University of Leipzig, Leipzig, Germany
3   Integrated Research and Treatment Center (IFB Adiposity Diseases), University of Leipzig, Leipzig, Germany
,
A. Körner
2   Center for Pediatric Research Leipzig, Department of Women’s and Child Health, University Hospital for Children & Adolescents, University of Leipzig, Leipzig, Germany
3   Integrated Research and Treatment Center (IFB Adiposity Diseases), University of Leipzig, Leipzig, Germany
,
W. Kiess
2   Center for Pediatric Research Leipzig, Department of Women’s and Child Health, University Hospital for Children & Adolescents, University of Leipzig, Leipzig, Germany
3   Integrated Research and Treatment Center (IFB Adiposity Diseases), University of Leipzig, Leipzig, Germany
,
M. Stumvoll
3   Integrated Research and Treatment Center (IFB Adiposity Diseases), University of Leipzig, Leipzig, Germany
4   Division of Endocrinology, Department of Medicine, University of Leipzig, Leipzig, Germany
,
A. Dietrich
3   Integrated Research and Treatment Center (IFB Adiposity Diseases), University of Leipzig, Leipzig, Germany
,
M. Blüher
3   Integrated Research and Treatment Center (IFB Adiposity Diseases), University of Leipzig, Leipzig, Germany
4   Division of Endocrinology, Department of Medicine, University of Leipzig, Leipzig, Germany
,
N. Klöting
3   Integrated Research and Treatment Center (IFB Adiposity Diseases), University of Leipzig, Leipzig, Germany
4   Division of Endocrinology, Department of Medicine, University of Leipzig, Leipzig, Germany
,
O. Söder
1   Department of Women and Child Health, Pediatric Endocrinology Unit, Karolinska Institutet, Stockholm, Sweden
,
K. Svechnikov
1   Department of Women and Child Health, Pediatric Endocrinology Unit, Karolinska Institutet, Stockholm, Sweden
› Institutsangaben
Weitere Informationen

Publikationsverlauf

received 16. Februar 2016

accepted 01. Juni 2016

Publikationsdatum:
29. Juni 2016 (online)

Auch verfügbar auf
    Lizenzen und Reprints

Abstract

Insulin-like peptide 5 (INSL5) is a gut hormone produced by L-cells in the colorectal epithelium and may play a role in the regulation of metabolic processes. The biological role of INSL5 is poorly investigated and nothing is known about the role of this hormone in obese and lean humans. Two cohorts were analyzed in the study. In the first cohort (n=76) the relationship between serum levels of INSL5 and different metabolic and hormonal parameters in obese and lean men and women were investigated. In the second cohort 14 male subjects underwent bariatric surgery. Circulating levels of INSL5 were then measured before and after interventions.

We report for the first time that circulating INSL5 interacts with multiple metabolic and hormonal variables in lean and obese men and women and is affected by bariatric surgery. Serum levels of INSL5 negatively correlated with testosterone and blood lipids but positively with cortisol in obese men. In contrast to males, obese women had a strong negative correlation of plasma levels of INSL5 with C-reactive protein (CRP). We observed that adipose tissue loss after bariatric surgery significantly reduced serum levels of INSL5 in obese men with and without Type 2 Diabetes Mellitus (T2DM) that was associated with the restoration of circulating levels of testosterone. All together, our data demonstrated that INSL5 may interact with some metabolic parameters in obese humans and this process is dependent of gender and obesity state.

Key words

INSL5 - adiposity - metabolic parameters - steroid hormones

Supporting Information

 

  • References

  • 1 Conklin D, Lofton-Day CE, Haldeman BA, Ching A, Whitmore TE, Lok S, Jaspers S. Identification of INSL5, a new member of the insulin superfamily. Genomics 1999; 60: 50-56
    CrossrefPubMedGoogle Scholar
  • 2 Burnicka-Turek O, Mohamed BA, Shirneshan K, Thanasupawat T, Hombach-Klonisch S, Klonisch T, Adham IM. INSL5-deficient mice display an alteration in glucose homeostasis and an impaired fertility. Endocrinology 2012; 153: 4655-4665
    CrossrefPubMedGoogle Scholar
  • 3 Akhter Hossain M, Bathgate RA, Kong CK, Shabanpoor F, Zhang S, Haugaard-Jonsson LM, Rosengren KJ, Tregear GW, Wade JD. Synthesis, conformation, and activity of human insulin-like peptide 5 (INSL5). ChemBioChem 2008; 9: 1816-1822
    CrossrefPubMedGoogle Scholar
  • 4 Dun SL, Brailoiu E, Wang Y, Brailoiu GC, Liu-Chen LY, Yang J, Chang JK, Dun NJ. Insulin-like peptide 5: expression in the mouse brain and mobilization of calcium. Endocrinology 2006; 147: 3243-3248
    CrossrefPubMedGoogle Scholar
  • 5 Grosse J, Heffron H, Burling K, Akhter Hossain M, Habib AM, Rogers GJ, Richards P, Larder R, Rimmington D, Adriaenssens AA, Parton L, Powell J, Binda M, Colledge WH, Doran J, Toyoda Y, Wade JD, Aparicio S, Carlton MB, Coll AP, Reimann F, O’Rahilly S, Gribble FM. Insulin-like peptide 5 is an orexigenic gastrointestinal hormone. Proc Natl Acad Sci USA 2014; 111: 11133-11138
    CrossrefPubMedGoogle Scholar
  • 6 Mashima H, Ohno H, Yamada Y, Sakai T, Ohnishi H. INSL5 may be a unique marker of colorectal endocrine cells and neuroendocrine tumors. Biochem Biophys Res Commun 2013; 432: 586-592
    CrossrefPubMedGoogle Scholar
  • 7 Chakaroun R, Raschpichler M, Kloting N, Oberbach A, Flehmig G, Kern M, Schon MR, Shang E, Lohmann T, Dressler M, Fasshauer M, Stumvoll M, Bluher M. Effects of weight loss and exercise on chemerin serum concentrations and adipose tissue expression in human obesity. Metabolism 2012; 61: 706-714
    CrossrefPubMedGoogle Scholar
  • 8 Loffler D, Muller U, Scheuermann K, Friebe D, Gesing J, Bielitz J, Erbs S, Landgraf K, Wagner IV, Kiess W, Korner A. Serum irisin levels are regulated by acute strenuous exercise. J Clin Endocrinol Metab 2015; 100: 1289-1299
    CrossrefPubMedGoogle Scholar
  • 9 Youn BS, Kloting N, Kratzsch J, Lee N, Park JW, Song ES, Ruschke K, Oberbach A, Fasshauer M, Stumvoll M, Bluher M. Serum vaspin concentrations in human obesity and type 2 diabetes. Diabetes 2008; 57: 372-377
    CrossrefPubMedGoogle Scholar
  • 10 Wiltberger G, Bucher JN, Schmelzle M, Hoffmeister A, Dietrich A. Preoperative Endoscopy and Its Impact on Perioperative Management in Bariatric Surgery. Digest Surg 2015; 32: 238-242
    CrossrefPubMedGoogle Scholar
  • 11 Rehfeld JF. The new biology of gastrointestinal hormones. Physiol Rev 1998; 78: 1087-1108
    PubMedGoogle Scholar
  • 12 Liu C, Chen J, Kuei C, Sutton S, Nepomuceno D, Bonaventure P, Lovenberg TW. Relaxin-3/insulin-like peptide 5 chimeric peptide, a selective ligand for G protein-coupled receptor (GPCR)135 and GPCR142 over leucine-rich repeat-containing G protein-coupled receptor 7. Mol Pharmacol 2005; 67: 231-240
    CrossrefPubMedGoogle Scholar
  • 13 Liu C, Kuei C, Sutton S, Chen J, Bonaventure P, Wu J, Nepomuceno D, Kamme F, Tran DT, Zhu J, Wilkinson T, Bathgate R, Eriste E, Sillard R, Lovenberg TW. INSL5 is a high affinity specific agonist for GPCR142 (GPR100). J Biol Chem 2005; 280: 292-300
    CrossrefPubMedGoogle Scholar
  • 14 Nilsson AC, Johansson-Boll EV, Bjorck IM. Increased gut hormones and insulin sensitivity index following a 3-d intervention with a barley kernel-based product: a randomised cross-over study in healthy middle-aged subjects. Br J Nutr 2015; 114: 899-907
    CrossrefPubMedGoogle Scholar