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Vol. 23, No. 1-3, 2009
Issue release date: 2009
Cell Physiol Biochem 2009;23:125–132
(DOI:10.1159/000204101)

Characterisation of the Insulinotropic Activity of an Aqueous Extract of Gymnema Sylvestre in Mouse β-Cells and Human Islets of Langerhans

Liu B. · Asare-Anane H. · Al-Romaiyan A. · Huang G.C.1 · Amiel S.A.1 · Jones P.M.1 · Persaud S.J.1
Beta Cell Development & Function Group and1Division of Gene & Cell Based Therapy, King’s College London
email Corresponding Author

Abstract

Leaves of the Gymnema sylvestre (GS) plant have been used to treat diabetes mellitus for millennia, but the previously documented insulin secretagogue effects of GS extracts in vitro may be non-physiological through damage to the β-cells. We have now examined the effects of a novel GS extract (termed OSA) on insulin secretion from the MIN6 β-cell line and isolated human islets of Langerhans. Insulin secretion from MIN6 cells was stimulated by OSA in a concentration-dependent manner, with low concentrations (0.06-0.25mg/ml) having no deleterious effects on MIN6 cell viability, while higher concentrations (≥0.5mg/ml) caused increased Trypan blue uptake. OSA increased β-cell Ca2+ levels, an effect that was mediated by Ca2+ influx through voltage-operated calcium channels. OSA also reversibly stimulated insulin secretion from isolated human islets and its insulin secretagogue effects in MIN6 cells and human islets were partially dependent on the presence of extracellular Ca2+. These data indicate that low concentrations of the GS isolate OSA stimulate insulin secretion in vitro, at least in part as a consequence of Ca2+ influx, without compromising β-cell viability. Identification of the component of the OSA extract that stimulates regulated insulin exocytosis, and further investigation of its mode(s) of action, may provide promising lead targets for Type 2 diabetes therapy.


 Outline


 goto top of outline Key Words

  • Islets of Langerhans
  • Insulin secretion
  • Plant-derived secretagogues

 goto top of outline Abstract

Leaves of the Gymnema sylvestre (GS) plant have been used to treat diabetes mellitus for millennia, but the previously documented insulin secretagogue effects of GS extracts in vitro may be non-physiological through damage to the β-cells. We have now examined the effects of a novel GS extract (termed OSA) on insulin secretion from the MIN6 β-cell line and isolated human islets of Langerhans. Insulin secretion from MIN6 cells was stimulated by OSA in a concentration-dependent manner, with low concentrations (0.06-0.25mg/ml) having no deleterious effects on MIN6 cell viability, while higher concentrations (≥0.5mg/ml) caused increased Trypan blue uptake. OSA increased β-cell Ca2+ levels, an effect that was mediated by Ca2+ influx through voltage-operated calcium channels. OSA also reversibly stimulated insulin secretion from isolated human islets and its insulin secretagogue effects in MIN6 cells and human islets were partially dependent on the presence of extracellular Ca2+. These data indicate that low concentrations of the GS isolate OSA stimulate insulin secretion in vitro, at least in part as a consequence of Ca2+ influx, without compromising β-cell viability. Identification of the component of the OSA extract that stimulates regulated insulin exocytosis, and further investigation of its mode(s) of action, may provide promising lead targets for Type 2 diabetes therapy.

Copyright © 2009 S. Karger AG, Basel


 goto top of outline Author Contacts

Shanta J Persaud
2.9N Hodgkin Building, King’s CollegeLondon
Guy’s campus, London SE1 1UL (UK)
Tel. +44-20-7848 6275, Fax: +44-20-7848 6280
E-Mail shanta.persaud@kcl.ac.uk


 goto top of outline Article Information

Accepted: December 11, 2008
Published online: February 18, 2009
Number of Print Pages : 8


 goto top of outline Publication Details

Cellular Physiology and Biochemistry (International Journal of Experimental Cellular Physiology, Biochemistry andPharmacology)

Vol. 23, No. 1-3, Year 2009 (Cover Date: 2009)

Journal Editor: F. Lang, Tübingen
ISSN: 1015–8987 (Print), eISSN: 1421–9778 (Online)

For additional information: http://www.karger.com/journals/cpb


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 or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
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 goverment 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.

Abstract

Leaves of the Gymnema sylvestre (GS) plant have been used to treat diabetes mellitus for millennia, but the previously documented insulin secretagogue effects of GS extracts in vitro may be non-physiological through damage to the β-cells. We have now examined the effects of a novel GS extract (termed OSA) on insulin secretion from the MIN6 β-cell line and isolated human islets of Langerhans. Insulin secretion from MIN6 cells was stimulated by OSA in a concentration-dependent manner, with low concentrations (0.06-0.25mg/ml) having no deleterious effects on MIN6 cell viability, while higher concentrations (≥0.5mg/ml) caused increased Trypan blue uptake. OSA increased β-cell Ca2+ levels, an effect that was mediated by Ca2+ influx through voltage-operated calcium channels. OSA also reversibly stimulated insulin secretion from isolated human islets and its insulin secretagogue effects in MIN6 cells and human islets were partially dependent on the presence of extracellular Ca2+. These data indicate that low concentrations of the GS isolate OSA stimulate insulin secretion in vitro, at least in part as a consequence of Ca2+ influx, without compromising β-cell viability. Identification of the component of the OSA extract that stimulates regulated insulin exocytosis, and further investigation of its mode(s) of action, may provide promising lead targets for Type 2 diabetes therapy.



 goto top of outline Author Contacts

Shanta J Persaud
2.9N Hodgkin Building, King’s CollegeLondon
Guy’s campus, London SE1 1UL (UK)
Tel. +44-20-7848 6275, Fax: +44-20-7848 6280
E-Mail shanta.persaud@kcl.ac.uk


 goto top of outline Article Information

Accepted: December 11, 2008
Published online: February 18, 2009
Number of Print Pages : 8


 goto top of outline Publication Details

Cellular Physiology and Biochemistry (International Journal of Experimental Cellular Physiology, Biochemistry andPharmacology)

Vol. 23, No. 1-3, Year 2009 (Cover Date: 2009)

Journal Editor: F. Lang, Tübingen
ISSN: 1015–8987 (Print), eISSN: 1421–9778 (Online)

For additional information: http://www.karger.com/journals/cpb


Copyright / Drug Dosage

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 or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
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 goverment 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.