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      Hypoglycemic Effects of Insulin-Like Growth Factor-1 in Experimental Uremia: Can Concomitant Growth Hormone Administration Prevent This Effect?

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          Abstract

          The risk of hypoglycemia limits the clinical application of insulin-like growth factor-1 (IGF-1). Our studies aimed to evaluate the mode of occurrence as well as the prevention of this side effect. Acute administration (i.v. infusion) of IGF-1 in subtotal nephrectomized uremic (U), sham-operated ad libitum fed control (C) and sham-operated pair-fed control (P) rats led to hypoglycemia, though more expressed in P. Serum glucose levels decreased within 60 min after the IGF-1 administration by 40% in U, by 45% in C and by 52% in P (p < 0.05, U vs. P). Chronic administration (7 days) of 1, 4 and 8 mg/kg/day IGF-1 in U rats led to hypoglycemia in an increasing manner as the dose of IGF-1 increased. On the first day, 2 h after injection, serum glucose levels were 116.5 ± 8.6, 110.4 ± 12.4, 60,3 ± 19.2 and 50.6 ± 18.3 mg/dl, respectively (p < 0.01). One week later, IGF-1 therapy proved to be less hypoglycemic in all the groups. On day 7, 2 h after injection the serum glucose levels were 118.9 ± 23.8, 89.0 ± 23.9 and 66.0 ± 32.0, respectively (in comparison to day 1 for 4 and 8 mg/kg/day IGF-1 p < 0.05). The combined effect of 4 mg/kg/day IGF-1 and 10 IU/kg/day growth hormone (GH) was also studied in U and P animals. Two hours after the first injections of IGF-1 serum glucose levels decreased in U from 120.0 ± 11.3 to 49.2 ± 21.6 mg/dl, while IGF-1 plus GH decreased the glucose level from 122.0 ± 15.5 to 81.3 ± 24.7 mg/dl (p < 0.05 IGF-1 vs. IGF-1 + GH). The hypoglycemic effect of IGF-1 was less expressed by long-term treatment and simultanous administration of GH overcame the glucose-lowering effect of IGF-1 (serum glucose levels on day 11 one hour after the injections: 73.7 ± 15.3 mg/dl with IGF-1, and 111.0 ± 7.8 mg/dl with IGF-1 + GH). Methylprednisolone (MP) did not significantly alter the former effects of IGF-1 and GH. In summary, IGF-1 leads to hypoglycemia in control and uremic rats in a dose-dependent manner. This effect becomes less expressed after prolonged administration. GH attenuates the hypoglycemic effect of IGF-1. This suggests that the combined GH and IGF-1 treatment is more effective and less dangerous in correcting uremic growth failure.

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          Author and article information

          Journal
          HRE
          Horm Res Paediatr
          10.1159/issn.1663-2818
          Hormone Research in Paediatrics
          S. Karger AG
          1663-2818
          1663-2826
          1999
          April 1999
          27 August 1999
          : 51
          : 4
          : 193-200
          Affiliations
          a2nd Department of Pediatrics and Institute of Patophysiology and International Nephrological Research and Training Center, Semmelweis University, Budapest, Hungary; bUniversity Children’s Hospital, Heidelberg, Germany
          Article
          23357 Horm Res 1999;51:193–200
          10.1159/000023357
          10474022
          © 1999 S. Karger AG, Basel

          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.

          Page count
          Figures: 1, Tables: 4, References: 32, Pages: 8
          Categories
          Original Paper

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