Skip to main content
SpringerLink
Log in

Increase in adiponectin levels during pioglitazone therapy in relation to glucose control, insulin resistance as well as ghrelin and resistin levels

  • Original Articles
  • Published:
Journal of Endocrinological Investigation Aims and scope Submit manuscript

Abstract

Glitazones increase the secretion of the adipocyte-derived hormone adiponectin. Furthermore, the gastric signal peptide ghrelin is known to suppress adiponectin expression in adipocyte cell culture models. It is not known whether the increase in adiponectin during glitazone therapy is due to a suppression of ghrelin levels, a decrease of resistin concentrations or an amelioration of glucose control. In 10 patients (age 71 ±9 yr, body mass index 29.9±3.6 kg/m2, HbA1c 6.9±0.5%) with Type 2 diabetes, who had already been treated with sulfonylureas, we additionally initiated a pioglitazone therapy (30 mg/day) for 12 weeks. To investigate the pioglitazone effect independently of blood glucose, glycosylated hemoglobin (HbA1c) was kept unchanged by reducing the daily dose of sulfonylurea if necessary. Ghrelin concentration [radioimmunoassay (RIA), Phoenix Pharmaceuticals, Mountain View, CA, USA], adiponectin levels [enzyme-linked immunosorbent assay (ELISA), Biovendor, Heidelberg, Germany] as well as resistin concentrations (ELISA, Linco Research, St. Charles, MO, USA) were measured before and after pioglitazone. Glucose control remained unchanged within the 12-week pioglitazone therapy (HbA1c 6.9±0.5% before vs 6.8±0.6% after pioglitazone) while body weight increased from 86.6±9.2 to 88.0±9.4 kg (p<0.05), and insulin concentration decreased from 19.6±5.7 to 10.1 ±1.6 μU/ml (p<0.05). Adiponectin concentration increased in all patients from 7.70±2.47 to 23.33±8.28 μg/ml (p<0.01), while resistin concentrations tended to decrease (by 15%; p=0.059). However, ghrelin remained unchanged during therapy. No correlations were observed either between ghrelin, resistin, insulin and adiponectin, or between body weight and hormone plasma levels. The increase in adiponectin levels during pioglitazone therapy seems to be at least partly independent of blood glucose and insulin concentration as well as of ghrelin levels, and it was not associated with a decrease in resistin concentrations. (J. Endocrinol. Invest. 29: 231–236, 2006)

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

Reference

  1. Nakano Y, Tobe T, Choi-Miura NH, Mazda T, Tomita T. Isolation and characterization of GBP28, a novel gelatin-binding protein purified from human plasma. J Biochem 1996, 120: 803–12.

    Article  PubMed  CAS  Google Scholar 

  2. Spranger J, Kroke A, Möhlig M, et al. Adiponectin and protection against type 2 diabetes mellitus. Lancet 2003, 361: 226–8.

    Article  PubMed  CAS  Google Scholar 

  3. Pischon T, Girman CJ, Hotamisligil GS, Rifai N, Hu FB, Rimm EB. Plasma adiponectin levels and risk of myocardial infarction in men. JAMA 2004, 291: 1730–7.

    Article  PubMed  CAS  Google Scholar 

  4. Dormandy JA, Charbonnel B, Eckland DJA, et al. Secondary prevention of macrovasular events in patients with type 2 diabetes in the PROactive Study (prospective pioglitazone clinical trial in macrovascular events): a randomized controlled trial. Lancet 2005, 366: 1279–89.

    Article  PubMed  CAS  Google Scholar 

  5. Marx N, Froehlich J, Siam L, et al. Antidiabetic PPAR gamma-activator rosiglitazone reduces MMP-9 serum levels in type 2 diabetic patients with coronary artery disease. Arterioscler Thromb Vasc Biol 2003, 23: 283–8.

    Article  PubMed  CAS  Google Scholar 

  6. Satoh N, Ogawa Y, Usui T, et al. Antiatherogenic effect of pioglitazone in type 2 diabetic patients irrespective of the responsiveness to its antidiabetic effect. Diabetes Care 2003, 26: 2493–9.

    Article  PubMed  CAS  Google Scholar 

  7. Maeda N, Takahashi M, Funahashi T, et al. PPARγ ligands increase expression and plasma concentrations of adiponectin, an adipose-derived protein. Diabetes 2001, 50: 2094–9.

    Article  PubMed  CAS  Google Scholar 

  8. Yang WS, Jeng CY, Wu TJ, et al. Synthetic peroxisome proliferator-activated receptor-γ agonist, rosiglitazone, increases plasma levels of adiponectin in type 2 diabetic patients. Diabetes Care 2002, 25: 376–80.

    Article  PubMed  CAS  Google Scholar 

  9. Steppan CM, Balley ST, Bhat S, et al. The hormone resistin links obesity to diabetes. Nature 2001, 409: 307–12.

    Article  PubMed  CAS  Google Scholar 

  10. Ott V, Fasshauer M, Dalski A, et al. Direct peripheral effects of ghrelin include suppression of adiponectin expression. Horm Metab Res 2002, 34: 640–5.

    Article  PubMed  CAS  Google Scholar 

  11. Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 1985, 28: 412–19.

    Article  PubMed  CAS  Google Scholar 

  12. Parhofer KG, Otto C, Geiss HC, Laubach E, Göke B. Effect of pioglitazone on lipids in well controlled patients with diabetes mellitus type 2 — results of a pilot study. Exp Clin Endocrinol Metab 2005, 113: 49–52.

    Article  CAS  Google Scholar 

  13. Berg AH, Combs TP, Du X, Brownlee M, Scherer P. The adipocyte-secreted protein ACRP30 enhances hepatic insulin action. Nature Med 2001, 7: 947–53.

    Article  PubMed  CAS  Google Scholar 

  14. Ouchi N, Kihara S, Arita Y, et al. Adipocyte-derived plasma protein, adiponectin, suppresses lipid accumulation and class A scavenger receptor expression in human monocyte-derived macrophages. Circulation 2001, 103: 1057–63.

    Article  PubMed  CAS  Google Scholar 

  15. Kondo H, Shimomura I, Matsukawa Y, et al. Association of adiponectin mutation with type 2 diabetes: a candidate gene for the insulin resistance syndrome. Diabetes 2002, 51: 2325–8.

    Article  PubMed  CAS  Google Scholar 

  16. Tonelli J, Li W, Kishore P, et al. Mechanisms of early insulin-sensitizing effects of thiazolidinediones in type 2 diabetes. Diabetes 2004, 53: 1621–9.

    Article  PubMed  CAS  Google Scholar 

  17. Yu JG, Javorschi S, Hevener AL, et al. The effect of thiazolidinediones on plasma adiponectin levels in normal, obese, and type 2 diabetic subjects. Diabetes 2002, 51: 2968–74.

    Article  PubMed  CAS  Google Scholar 

  18. Iwaki M, Matsuda M, Maeda N, et al. Induction of adiponectin, a fat-derived antidiabetic and antiatherogenic factor, by nuclear receptors. Diabetes 2003, 52: 1655–63.

    Article  PubMed  CAS  Google Scholar 

  19. Fasshauer M, Klein J, Neumann S, Eszlinger M, Paschke R. Hormonal regulation of adiponectin gene expression in 3T3-L1 adipocytes. Biochem Biophys Res Comm 2002, 290: 1084–9.

    Article  PubMed  CAS  Google Scholar 

  20. Möhlig M, Wegewitz U, Osterhoff M, et al. Insulin decreases human adiponectin plasma levels. Horm Metab Res 2002, 34: 655–8.

    Article  PubMed  Google Scholar 

  21. Poykko SM, Kellokoski E, Horkko S, Kauma H, Kesaniemi YA, Ukkola O. Low plasma ghrelin is associated with insulin resistance, hypertension, and the prevalence of type 2 diabetes. Diabetes 2003, 52: 2546–53.

    Article  PubMed  Google Scholar 

  22. Purnell JQ, Weigle DS, Breen P, Cummings DE. Ghrelin levels correlate with insulin levels, insulin resistance, and high-density lipoprotein cholesterol, but not with gender, menopausal status, or cortisol levels in humans. J Clin Endocrinol Metab 2003, 88: 5747–52.

    Article  PubMed  CAS  Google Scholar 

  23. McLaughlin T, Abbasi F, Lamendola C, Frayo RS, Cummings DE. Plasma ghrelin concentrations are decreased in insulin-resistant obese adults relative to equally obese insulin sensitive controls. J Clin Endocrin Metab 2004, 89: 1630–5.

    Article  CAS  Google Scholar 

  24. Akamizu T, Shinomiya T, Irako T, et al. Separate measurement of plasma levels of acylated and desacyl ghrelin in healthy subjects using a new direct ELISA assay. J Clin Endocrin Metab 2005, 90: 6–9

    Article  CAS  Google Scholar 

  25. Bajaj M, Suraamornkul S, Hardies LJ, Pratipanawatr T, DeFronzo RA. Plasma resistin concentration, hepatic fat content, and hepatic and peripheral insulin resistance in pioglitazone-treated type II diabetic patients. Int J Obes 2004, 28: 783–9.

    Article  CAS  Google Scholar 

  26. Song H, Shojima N, Sakoda H, et al. Resistin is regulated by C/EBPs, PPARs, and signal-transducing molecules. Biochem Biophys Res Commun 2002, 299: 291–8.

    Article  PubMed  CAS  Google Scholar 

  27. Fukuen S, Iwaki M, Yasui A, Makishima M, Matsuda M, Shimimura I. Sulfonylurea agents exhibit peroxisome proliferator-activated receptor gamma agonistic activity. J Biol Chem 2005, 260: 23653–9.

    Article  CAS  Google Scholar 

  28. Pajvani UB, Hawkins M, Combs TP, et al. Complex distribution, not absolute amount of adiponectin, correlates with thiazolidinedione-mediated improvement in insulin sensitivity. J Biol Chem 2004, 279: 12152–62.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Medical Department 2, Grosshadern, University Hospital of Munich, Marchioninistrasse 15, D-81377, Munich, Germany

    C. Otto MD, B. Göke, M. Lehrke & K. G. Parhofer

  2. Medical Department - Innenstadt, Germany

    B. Otto

  3. Department of Clinical Nutrition, German Institute of Human Nutrition, Bergholz-Rehbrücke, Germany

    A. F. H. Pfeiffer & J. Spranger

  4. Department of Medicine, The Penn Diabetes Center, University of Pennsylvania School of Medicine, Philadelphia, USA

    M. Lehrke

  5. Institute of Clinical Chemistry - Grosshadern, University Hospital Munich, Germany

    M. Vogeser

  6. Department of Endocrinology, Diabetes and Nutrition, Charité-Universitymedicine Berlin, Campus Benjamin Franklin, Germany

    A. F. H. Pfeiffer & J. Spranger

Authors
  1. C. Otto MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. B. Otto
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. B. Göke
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. A. F. H. Pfeiffer
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. M. Lehrke
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. M. Vogeser
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. J. Spranger
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. K. G. Parhofer
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to C. Otto MD.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Otto, C., Otto, B., Göke, B. et al. Increase in adiponectin levels during pioglitazone therapy in relation to glucose control, insulin resistance as well as ghrelin and resistin levels. J Endocrinol Invest 29, 231–236 (2006). https://doi.org/10.1007/BF03345545

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF03345545

Key Words

Search

Navigation