Screening of clinical medicines for effects on gene expressions and protein productions of adipocytokines by using a newly-isolated preadipocyte line

2004 Fiscal Year Final Research Report Summary

• Project/Area Number: 15590926
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Metabolomics
• Research Institution: Iwate Medical University
• Principal Investigator: SATOH Jo Iwate Medical University, School of Medicine, Professor, 医学部, 教授 (60125565)
• Co-Investigator(Kenkyū-buntansha): DOI Hideyuki Tohoku University, Tohoku University Hospital, Assistant Professor, 助教授 (90188839) ; TAKAHASHI Kazuma Tohoku University, Tohoku University Hospital, Assistant Professor, 助手 (60292215) ; KANEKO Yoshihito Iwate Medical University, School of Medicine, Lecturer, 医学部, 講師 (80285585) ; ISHIDA Wataru Iwate Medical University, School of Medicine, Assistant Professor, 医学部, 助手 (80305995)
• Project Period (FY): 2003 – 2004
• Keywords: Adipocytes / AP-18 / Adiponectin / TNF-aloha / Glucose transnorter-4 / Gliclazide / Glibenclamide / Pioglitazone

Research Abstract

We have shown that the AP-18 cell, an preadipocyte line newly isolated from subcutaneous tissue of the 03H/He mouse, expresses various adipocyte-specific and adipocyte?related genes, and spontaneously differentiates to mature adipocyte during culture with insulin.
Using AP-1 8 cells in vitro, we observed effects of various clinical medicines used for diabetic patients on gene expressions of adiponectin and GLUT4, and on production of adiponectin protein. Gliclazide and glibenclamide (sulfonylureas), pioglitazone (thiazolidinedione), and delapril (ACE inhibitor) increased gene expressions of adiponectin and GLUT4, and adiponectin protein production, whereas metformin (biguanide), temocapril and captopril (ACE inhibitors), candesartane (ARB), doxazosine (alpha-i blocker), metprolol and selectol (beta-1 blockers), and methylcysteine (cysteinderivative) had no such effects.
Because it has been indicated that sulfonylurea stimulates adipocytes to produce adiponectin, we measured serum concentration of adipocytekines including adiponectin, TNF-alpha, IL-i-beta, IL-6 and leptin in patients (n = 14 ? 16) treated with gliclazide or glibenclimide to observe in vivo effects of these medicines. There was a tendency that serum adiponecitn concentration was higher in patients treated with gliclazide than those with glibenclimide, and serum TN F-alpha concentration was vice versa, although sample size was small.
The study using AP-i8 cells indicates that sulfonylurea increases gene expressions of adiponectin and GLUT-4, and production of adiponecitn protein.

Research Products

• [Journal Article] Liver fat content measured by magnetic resonance spectroscopy at 3.0-tesla independently correlates with plasminogen activator inhibitor-1 and body mass index in type 2 diabetic subjects. (2005)
  • Author(s): Ishii M, Yoshioka Y, Ishida W, Kaneko Y, Fujiwara F, Taneichi H, Miura M, Toshihiro M, Takebe N, Iwai M, Suzuki K, Satoh I.
  • Journal Title: Tohoku J Exp Med. 206(1) Pages: 23-30
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Low incidence of vascular complications in patients with diabetes mellitus associated with liver cirrhosis as compared with type 2 diabetes mellitus. (2005)
  • Author(s): Fujiwara F, Ishii M, Taneichi H, Miura M, Toshihiro M, Takebe N, Ishida W, Kaneko Y, Kato A, Suzuki K, Satoh J
  • Journal Title: Tohoku J Exp Med. 205(4) Pages: 327-334
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Low incidence of vascular complications in patients with diabetes mellitus associated with liver cirrhosis as corn ared with t e 2 diabetes mellitus. (2005)
  • Author(s): Fujiwara F, Ishil M, Taneichi H, Miura M, Toshihiro M, Takebe N, Ishida W, Kaneko Y, KatoA, Suzuki K, Satoh J
  • Journal Title: Tohoku J Exp Med. 205(4) Pages: 327-334
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Liver fat content measured by magnetic resonance spectroscopy at 3.0-tesla independently correlates with plasminogen activator inhibitor-i and body mass index in type 2 diabetic subjects. (2005)
  • Author(s): lshii M, Yoshioka Y, Ishida W, Kaneko Y, Fujiwara F, Taneichi H, Miura M, Toshihiro M, Takebe N, lwai M, Suzuki K, Satoh J.
  • Journal Title: Tohoku J Exp Med. 206(1) Pages: 23-30
  • Description: 「研究成果報告書概要(欧文)」より