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Horm Metab Res 2011; 43(11): 766-773
DOI: 10.1055/s-0031-1287793
Original Basic
© Georg Thieme Verlag KG Stuttgart · New York

Mechanisms of p-Methoxycinnamic Acid-induced Increase in Insulin Secretion

S. Adisakwattana
1   Department of Pharmacology, Faculty of Veterinary Science, Chulalongkorn University, Bangkok, Thailand
,
W. H. Hsu
2   Department of Biomedical Sciences, Iowa State University, Ames, Iowa, USA
,
S. Yibchok-anun
1   Department of Pharmacology, Faculty of Veterinary Science, Chulalongkorn University, Bangkok, Thailand
› Author Affiliations
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Publication History

received28 May 2011

accepted 29 August 2011

Publication Date:
18 October 2011 (online)

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Abstract

p-Methoxycinnamic acid (p-MCA) is a cinnamic acid derivative that shows various pharmacologic actions such as hepatoprotective and antihyperglycemic activities. The present study was to elucidate the mechanisms by which p-MCA increases [Ca2+]i and insulin secretion in INS-1 cells. p-MCA (100 μM) increased [Ca2+]i in INS-1 cells. The p-MCA-induced insulin secretion and rise in [Ca2+]i were markedly inhibited in the absence of extracellular Ca2+ or in the presence of an L-type Ca2+ channel blocker nimodipine. These results suggested that p-MCA increased Ca2+ influx via the L-type Ca2+ channels. Diazoxide, an ATP-sensitive K+ channel opener, did not alter p-MCA-induced insulin secretion, nor [Ca2+]i response. In addition, p-MCA enhanced glucose-, glibenclamide-induced insulin secretion whereas it also potentiated the increase in insulin secretion induced by arginine, and Bay K 8644, an L-type Ca2+ channel agonist. Taken together, our results suggest that p-MCA stimulated insulin secretion from pancreatic β-cells by increasing Ca2+ influx via the L-type Ca2+ channels, but not through the closure of ATP-sensitive K+ channels.

Key words

p-methoxycinnamic acid - diabetes - insulin secretion - INS-1 cells - Ca2+ influx
 

  • References

  • 1 Ashcroft FM. ATP-sensitive potassium channelopathies: focus on insulin secretion. J Clin Invest 2005; 115: 2047-2058
    CrossrefPubMedGoogle Scholar
  • 2 Renström E, Barg S, Thévenod F, Rorsman P. Sulfonylurea-mediated stimulation of insulin exocytosis via an ATP-sensitive K+ channel-independent action. Diabetes 2002; 51 (Suppl. 01) S33-S36
    CrossrefPubMedGoogle Scholar
  • 3 Rajan AS, Aguilar-Bryan L, Nelson DA, Yaney GC, Hsu WH, Kunze DL, Boyd AE. Ion channels and insulin secretion. Diabetes Care 1990; 13: 340-363
    CrossrefPubMedGoogle Scholar
  • 4 Jackson JE, Bressler R. Clinical pharmacology of sulphonylurea hypoglycaemic agents. (part 1) Drugs 1981; 22: 211-245
    CrossrefPubMedGoogle Scholar
  • 5 Ferner RE. Neil HAW. Sulphonylureas and hypoglycaemia. Br Med J 1988; 296: 949-950
    CrossrefPubMedGoogle Scholar
  • 6 Gerich JE. Oral hypoglycemic agents. N Engl J Med 1989; 321: 1231-1245
    CrossrefPubMedGoogle Scholar
  • 7 Jennings A, Wilson R, Ward J. Symptomatic hypoglycemia in NIDDM patients treated with oral hypoglycemic agents. Diabetes Care 1989; 12: 203-208
    CrossrefPubMedGoogle Scholar
  • 8 Perez-Alvarez V, Bobadilla RA, Muriel P. Structure-hepatoprotective activity relationship of 3,4-dihydroxycinnamic acid (caffeic acid) derivatives. J Appl Toxicol 2001; 21: 527-531
    CrossrefPubMedGoogle Scholar
  • 9 Wiesner J, Mitsch A, Wissner P, Jomaa H, Schlitzer M. Structure-activity relationships of novel anti-malarial agents. Part 2: cinnamic acid derivatives. Bioorg Med Chem Lett 2001; 11: 423-424
    CrossrefPubMedGoogle Scholar
  • 10 Natella F, Nardini M, Di Felice M, Scaccini C. Benzoic and cinnamic acid derivatives as antioxidants: structure-activity relation. J Agric Food Chem 1999; 47: 1453-1459
    CrossrefPubMedGoogle Scholar
  • 11 Liu IM, Chi TC, Hsu FL, Chen CF, Cheng JT. Isoferulic acid as active principle from the rhizoma of Cimicifuga dahurica to lower plasma glucose in diabetic rats. Planta Med 1999; 65: 712-714
    Article in Thieme ConnectPubMedGoogle Scholar
  • 12 Nomura E, Kashiwada A, Hosoda A, Nakamura K, Morishita H, Tsuno T, Taniguchi H. Synthesis of amide compounds of ferulic acid, and their stimulatory effects on insulin secretion in vitro. Bioorg Med Chem 2003; 11: 3807-3813
    CrossrefPubMedGoogle Scholar
  • 13 Adisakwattana S, Moonsan P, Yibchok-Anun S. Insulin-releasing properties of a series of cinnamic acid derivatives in vitro and in vivo. J Agric Food Chem 2008; 56: 7838-7844
    CrossrefPubMedGoogle Scholar
  • 14 Adisakwattana S, Chantarasinlapin P, Thammarat H, Yibchok-Anun S. A series of cinnamic acid derivatives and their inhibitory activity on intestinal alpha-glucosidase. J Enzyme Inhib Med Chem 2009; 24: 1194-2000
    CrossrefPubMedGoogle Scholar
  • 15 Kim SR, Kang SY, Lee KY, Kim SH, Markelonis GJ, Oh TH, Kim YC. Anti-amnestic activity of E-p-methoxycinnamic acid from Scrophularia buergeriana . Brain Res Cogn Brain Res 2003; 17: 454-461
    CrossrefPubMedGoogle Scholar
  • 16 Bylka W. E- and Z-p-methoxycinnamic acid from Aquilegia vulgaris . Acta Pol Pharm 2004; 61: 307-308
    PubMedGoogle Scholar
  • 17 Lee EJ, Kim SR, Kim J, Kim YC. Hepatoprotective phenylpropanoids from Scrophularia buergeriana roots against CCl4-induced toxicity: action mechanism and structure-activity relationship. Planta Med 2002; 68: 407-411
    Article in Thieme ConnectPubMedGoogle Scholar
  • 18 Kim SR, Sung SH, Jang YP, Markelonis GJ, Oh TH, Kim YC. E-p-methoxycinnamic acid protects cultured neuronal cells against neurotoxicity induced by glutamate. Br J Pharmacol 2002; 135: 1281-1291
    CrossrefPubMedGoogle Scholar
  • 19 Adisakwattana S, Sookkongwaree K, Roengsumran S, Petsom A, Ngamrojnavanich N, Chavasiri W, Deesamer S, Yibchok-anun S. Structure-activity relationships of trans-cinnamic acid derivatives on alpha-glucosidase inhibition. Bioorg Med Chem Lett 2004; 14: 2893-2896
    CrossrefPubMedGoogle Scholar
  • 20 Yibchok-Anun S, Adisakwattana S, Moonsan P, Hsu WH. Insulin secretagogue activity of p-methoxycinnamic acid in rats, perfused rat pancreas and pancreatic β-cell line. Basic Clin Pharmacol Toxicol 2008; 102: 476-482
    CrossrefPubMedGoogle Scholar
  • 21 Adisakwattana S, Roengsamran S, Hsu WH, Yibchok-Anun S. Mechanisms of antihyperglycemic effect of p-methoxycinnamic acid in normal and streptozotocin-induced diabetic rats. Life Sci 2005; 78: 406-412
    CrossrefPubMedGoogle Scholar
  • 22 Hsu WH, Xiang HD, Rajan AS, Kunze DL, Boyd 3rd AE. Somatostatin inhibits insulin secretion by a G-protein-mediated decrease in Ca2+ entry through voltage-dependent Ca2+ channels in the beta cell. J Biol Chem 1991; 266: 837-843
    PubMedGoogle Scholar
  • 23 Cheng H, Grodnitzky JA, Yibchok-anun S, Ding J, Hsu WH. Somatostatin increases phospholipase D activity and phosphatidylinositol 4.5-bisphosphate synthesis in clonal β-cells HIT-T15. Mol Pharmacol 2005; 67: 2162-2172
    CrossrefPubMedGoogle Scholar
  • 24 Yibchok-Anun S, Jittaprasatsin W, Somtir D, Bunlunara W, Adisakwattana S. Insulin secreting and α-glucosidase inhibitory activity of Coscinium fenestratum and postprandial hyperglycemia in normal and diabetic rats. J Med Plants Res 2009; 3: 646-651
    PubMedGoogle Scholar
  • 25 Ämmälä C, Moorhouse A, Ashcroft FM. The sulphonylurea receptor confers diazoxide sensitivity on the inwardly rectifying K+ channel Kir6.1 expressed in human embryonic kidney cells. J Physiol 1996; 494: 709-714
    PubMedGoogle Scholar
  • 26 Park KH, Song SC, Akaike T. Determination of the specific interaction between sulfonylurea-incorporated polymer and rat islets. J Biochem (Tokyo) 2002; 131: 359-364
    CrossrefPubMedGoogle Scholar
  • 27 Pedersen SF, Owsianik G, Nilius B. TRP channels: an overview. Cell Calcium 2005; 38: 233-252
    CrossrefPubMedGoogle Scholar
  • 28 Bandell M, Story GM, Hwang SW, Viswanath V, Eid SR, Petrus MJ, Earley TJ, Patapoutian A. Noxious cold ion channel TRPA1 is activated by pungent compounds and bradykinin. Neuron 2004; 41: 849-857
    CrossrefPubMedGoogle Scholar
  • 29 Liu Z, Jeppesen PB, Gregersen S, Chen X, Hermansen K. Dose- and glucose-dependent effects of amino acids on insulin secretion from isolated mouse islets and clonal INS-1E beta-cells. Rev Diabet Stud 2008; 5: 232-244
    CrossrefPubMedGoogle Scholar
  • 31 Thams P, Capito K. l-Arginine stimulation of glucose-induced insulin secretion through membrane depolarization and independent of nitric oxide. Eur J Endocrinol 1999; 140: 87-93
    CrossrefPubMedGoogle Scholar
  • 30 Piatti PM, Monti LD, Valsecchi G, Magni F, Setola E, Marchesi F, Galli-Kienle M, Pozza G, Alberti KG. Long-Term oral l-arginine administration improves peripheral and hepatic insulin sensitivity in type 2 diabetic patients. Diabetes Care 2001; 24: 875-880
    Google Scholar
  • 32 Striessnig J, Murphy BJ, Catterall WA. Dihydropyridine receptor of L-type Ca2+ channels: identification of binding domains for [3H](+)-PN200-110 and [3H]azidopine within the alpha 1 subunit. Proc Natl Acad Sci USA 1991; 88: 10769-10773
    CrossrefPubMedGoogle Scholar
  • 33 Skasa M, Jungling E, Picht E, Schondube F, Luckhoff A. L-type calcium currents in atrial myocytes from patients with persistent and non-persistent atrial fibrillation. Basic Res Cardiol 2001; 96: 151-159
    CrossrefPubMedGoogle Scholar
  • 34 Larsson-Nyren G, Sehlin J. Comparison of the effects of perchlorate and Bay K 8644 on the dynamics of cytoplasmic Ca2+ concentration and insulin secretion in mouse beta-cells. Biochem J 1996; 314: 167-173
    PubMedGoogle Scholar
  • 35 Hofmann F, Lacinova L, Klugbauer N. Voltage-dependent calcium channels: from structure to function. Rev Physiol Biochem Pharmacol 1999; 139: 33-87
    PubMedGoogle Scholar