Bioactive compound(s) extracted from cinnamon potentiate insulin activity, as measured by glucose oxidation in the rat epididymal fat cell assay. Wortmannin, a potent PI 3′-kinase inhibitor, decreases the biological response to insulin and bioactive compound(s) from cinnamon similarly, indicating that cinnamon is affecting an element(s) upstream of PI 3′-kinase. Enzyme studies done in vitro show that the bioactive compound(s) can stimulate autophosphorylation of a truncated form of the insulin receptor and can inhibit PTP-1, a rat homolog of a tyrosine phosphatase (PTP-1B) that inactivates the insulin receptor. No inhibition was found with alkaline phosphate or calcineurin suggesting that the active material is not a general phosphatase inhibitor. It is suggested, then, that a cinnamon compound(s), like insulin, affects protein phosphorylation-dephosphorylation reactions in the intact adipocyte. Bioactive cinnamon compounds may find further use in studies of insulin resistance in adult-onset diabetes.

Sasson S, Ashhab Y, Melloul D, Cerasi E: Autoregulation of glucose transport: Effects of glucose transporter expression and cellular location in muscle; in Ostenson CG, Efendic S, Vranic M (eds): New Concept in the Pathogenesis of NIDDM. New York, Plenum Press, 1993, pp 113–127.
Olefsky JM: Insulin resistance and the pathogenesis of non-insulin-dependent diabetes mellitus: Cellular and molecular mechanisms; in Ostenson CG, Efendic S, Vranic M (eds): New Concepts in the Pathogenesis of NIDDM. New York, Plenum Press, 1993, pp 129–150.
Moller DE, Flier JS: Insulin resistance – Mechanisms, syndromes, and implications. N Engl J Med 1991;325:938–948.
Almind K, Bjorbaek C, Vestergaard H, Hansen T, Echwald S, Pederson O: Amino acid polymorphisms of insulin receptor substrate-1 in non-insulin-dependent diabetes mellitus. Lancet 1993;342:828–832.
Imamura T, Takata Y, Morioka H, Haruto T, Sawa T, Iwanishi M, Hu YG, Suzuki Y, Hamada J, Kobayashi M: Two naturally occurring mutations in the kinase domain of the insulin receptor accelerate degradation of the insulin receptor and impair the kinase activity. J Biol Chem 1994;269:31019–31027.
Maddux BA, Sbraccia P, Kumakura S, Sasson S, Youngren S, Fisher A, Spencer S, Grupe A, Henzel W, Stewart TA, Reaven GM, Goldfine ID: Membrane glycoprotein PC-1 and insulin resistance in non-insulin-dependent diabetes mellitus. Nature 1995;373:448–451.
Thies RS, Molina JM, Ciaraldi TP, Freidenberg GR, Olefsky JM: Insulin-receptor autophosphorylation and endogenous substrate phosphorylation in human adipocytes from control, obese, and NIDDM subjects. Diabetes 1990;39:250–259.
Goddyear LJ, Giorgino F, Sherman LA, Carey J, Smith RJ, Dohm GL: Insulin receptor phosphorylation, insulin receptor substrate-1 phosphorylation, and phosphatidylinositol 3-kinase activity are decreased in intact skeletal muscle strips from obese subjects. J Clin Invest 1995;95:2195–2204.
Nadiv O, Cohen O, Zick Y: Defects in insulin’s signal transduction in old rat livers. Endocrinology 1992;130:1515–1524.
King MJ, Sharma RP, Sale GJ: Site-specific dephosphorylation and deactivation of the human insulin receptor tyrosine kinase by particulate and soluble phosphotyrosyl protein phosphatases. Biochem J 1991;275:413–418.
Nadiv O, Shinitzky M, Manu H, Hecht D, Roberts CT, LeRoith D, Zick Y: Elevated protein tyrosine phosphatase activity and increased membrane viscosity are associated with impaired activation of the insulin receptor kinase in old rats. Biochem J 1994;298:443–450.
Begum N, Sussman KE, Draznin B: Differential effects of diabetes on adipocyte and liver phosphotyrosine and phosphoserine phosphatase activities. Diabetes 1991;40:1620–1629.
Ahmad F, Goldstein BJ: Alterations in specific protein-tyrosine phosphatases accompany insulin resistance of streptozotocin diabetes. Am J Physiol 1995;268:E932–E940.
Ahmad F, Goldstein BJ: Increased abundance of specific skeletal muscle protein-tyrosine phosphatases in a genetic model of insulin-resistant obesity and diabetes mellitus. Metabolism 1995;44:1175–1184.
Ramachandran C, Aebersold R, Tonks NK, Pot DA: Sequential dephosphorylation of a multiply phosphorylated insulin receptor peptide by protein tyrosine phosphatase. Biochemistry 1992;31:4232–4238.
Seely BL, Staubs PA, Reichart DR, Berhau P, Milarski KL, Saltiel AR, Kusari J, Olefsky JM: Protein tyrosine phosphatase 1B interacts with the activated insulin receptor. Diabetes 1996;45:1379–1385.
Bandyopadhyay D, Kusari A, Kenner KA, Liu F, Chernoff J, Gustafson TA, Kusari J: Protein-tyrosine phosphatase 1B complexes with the insulin receptor in vivo and is tyrosine-phosphorylated in the presence of insulin. J Biol Chem 1997;272:1639–1645.
Lammers R, Bossenmaier B, Cool DE, Tonks NE, Schlessinger J, Fischer EH, Ullrich A: Differential activities of protein tyrosine phosphatase in intact cells. J Biol Chem 1993;268:22456–22462.
Kenner KA, Anyanwu E, Olefsky JM, Kusari J: Protein-tyrosine phosphatase 1B is a negative regulator of insulin- and insulin-like growth factor-I-stimulated signaling. J Biol Chem 1996;271:19810–19816.
Hashimoto N, Goldstein BJ: Differential regulation of mRNAs encoding three protein tyrosine phosphatases by insulin and activation of protein kinase C. Biochem Biophys Res Commun 1992;188:1305–1311.
Khan A, Bryden NA, Polansky MM, Anderson RA: Insulin potentiating factor and chromium content of selected food and spices. Biol Trace Element Res 1990;24:183–188.
Berrio LF, Polansky MM, Anderson RA: Insulin activity: Stimulatory effects of cinnamon and brewer’s yeast as influenced by albumin. Horm Res 1992;37:225–229.
Mertz W: Chromium in human nutrition. Physiol Rev 1969;49:163–239.
Anderson RA, Brantner JH, Polansky MM: An improved assay for biologically active chromium. J Agric Food Chem 1978;26:1219–1221.
Tuman RW, Bilbo JT, Doisy RJ: Comparison and effects of natural and synthetic glucose tolerance factor in normal and genetically diabetic mice. Diabetes 1978;27:49–56.
Schwartz K, Mertz W: Letter to the editor. Chromium (III) and the glucose tolerance factor. Arch Biochem Biophys 1959;85:292–295.
Anderson RA, Polansky MM, Bryden NA, Roginski EE, Mertz M, Glinsman W: Chromium supplementation of human subjects: Effects on glucose, insulin, and lipid variables. Metabolism 1983;32:894–899.
Anderson RA, Polansky MM, Bryden NA, Canary JJ: Supplemental-chromium effects on glucose, insulin, glucagon, and urinary chromium losses in subjects consuming controlled low-chromium diets. Am J Clin Nutr 1991;54:909–916.
Guan K, Dixon JE: Eukaryotic proteins expressed in Escherichia coli: An improved thrombin cleavage and purification procedure of fusion proteins with glutathione S-transferase. Anal Biochem 1991;192:262–267.
Herrera R, Lebwohl D, de Herreros AG, Kallen RG, Rosen OM: Synthesis, purification, and characterization of the cytoplasmic domain of the human insulin receptor using a baculovirus expression system. J Biol Chem 1988;263:5560–5568.
Perrino BA, Ng LY, Soderling TR: Calcium regulation of calcineurin phosphatase activity by its B subunit and calmodulin. J Biol Chem 1995;270:340–346.
Hippen KL, Jakes S, Richards J, Jena BP, Beck BL, Tabatabai LB, Ingebritsen TS: Acidic residues are involved in substrate recognition by two soluble protein tyrosine phosphatases, PTP-5 and rrbPTP-1. Biochemistry 1993;32:12405–12412.
Weisinger D, Gubler HU, Haefliger W, Hauser D: Anti-inflammatory activity of the new mould metabolite 11-desacetoxy-wortmannin and some of its derivatives. Experientia 1974;30:135–136.
Okada T, Sakuma L, Fukui Y, Hazeki O, Ui M: Blockage of chemotactic peptide-induced stimulation of neutrophils by wortmannin as a result of selective inhibition of phosphatidylinositol kinase. J Biol Chem 1994;269:3563–3567.
Kanai F, Ito K, Todaka M, Hayashi O, Kamohara S, Ishii K, Okada T, Haxekie O, Ui M, Ebina Y: Insulin-stimulated Glut4 translocation is relevant to the phosphorylation of IRS-1 and the activity of PI3-kinase. Biochem Biophys Res Commun 1993;195:762–768.
Garen A, Levinthal C: A fine-structure genetic and chemical study of the enzyme alkaline phosphatase of E. coli. Biochim Biophys Acta 1960;38:470–483.
Stewart AA, Ingebritsen TS, Manalan A, Klee CB, Cohen P: Discovery of a Ca2+- and calmodulin-dependent protein phosphatase. FEBS Lett 1982;137:80–84.
Yang SD, Tallant EA, Cheung WY: Calcineurin is a calmodulin-dependent protein phosphatase. Biochem Biophys Res Commun 1982;105:1419–1425.
Cheatham B, Kahn CR: Insulin action and the insulin signaling network. Endocr Rev 1995;16:117–142.
Hotamisligil GS, Peraldi P, Budavari A, Ellis R, White MF, Spiegelman BM: IRS-1-mediated inhibition of insulin receptor kinase activity in TNF-alpha- and obesity-induced insulin resistance. Science 1996;271:665–668.
Takehide O, Isobe T, Ichimura T, Taoke M, Funaki M, Sakoda H, Onishi Y, Inukai K, Anai M, Fukushima Y, Kikichi M, Yazaki Y, Oka Y, Asano T: 14-3-3 protein binds to insulin receptor substrate-1, one of the binding sites of which is in the phosphotyrosine binding domain. J Biol Chem 1997;272:25267–25274.
Eldar-Finkelman H, Krebs EG: Phosphorylation of IRS-1 by glycogen synthase kinase-3 impairs insulin action. Proc Natl Acad Sci 1997;94:9660–9664.
Akiyama T, Ishida J, Nakagawa S, Ogawara H, Watanabe S, Itoh N, Shibuya M, Fukami Y: Genistein, a specific inhibitor of tyrosine-specific kinases. J Biol Chem 1987;262:5592–5595.
Imparl JM, Senshu T, Graves DJ: Studies of calcineurin-calmodulin interaction: Probing the role of arginine residues using peptidylarginine deiminase. Arch Biochem Biophys 1995;318:370–377.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.