Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
  • Clinical Research and Public Health
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Gastroenterology
    • Immunology
    • Metabolism
    • Nephrology
    • Neuroscience
    • Oncology
    • Pulmonology
    • Vascular biology
    • All ...
  • Videos
    • Conversations with Giants in Medicine
    • Video Abstracts
  • Reviews
    • View all reviews ...
    • Complement Biology and Therapeutics (May 2025)
    • Evolving insights into MASLD and MASH pathogenesis and treatment (Apr 2025)
    • Microbiome in Health and Disease (Feb 2025)
    • Substance Use Disorders (Oct 2024)
    • Clonal Hematopoiesis (Oct 2024)
    • Sex Differences in Medicine (Sep 2024)
    • Vascular Malformations (Apr 2024)
    • View all review series ...
  • Viewpoint
  • Collections
    • In-Press Preview
    • Clinical Research and Public Health
    • Research Letters
    • Letters to the Editor
    • Editorials
    • Commentaries
    • Editor's notes
    • Reviews
    • Viewpoints
    • 100th anniversary
    • Top read articles

  • Current issue
  • Past issues
  • Specialties
  • Reviews
  • Review series
  • Conversations with Giants in Medicine
  • Video Abstracts
  • In-Press Preview
  • Clinical Research and Public Health
  • Research Letters
  • Letters to the Editor
  • Editorials
  • Commentaries
  • Editor's notes
  • Reviews
  • Viewpoints
  • 100th anniversary
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
Top
  • View PDF
  • Download citation information
  • Send a comment
  • Terms of use
  • Standard abbreviations
  • Need help? Email the journal
  • Top
  • Abstract
  • Version history
  • Article usage
  • Citations to this article

Advertisement

Research Article Free access | 10.1172/JCI114142

Glucose and free fatty acid metabolism in non-insulin-dependent diabetes mellitus. Evidence for multiple sites of insulin resistance

Leif C. Groop, Riccardo C. Bonadonna, Stefano DelPrato, Klaus Ratheiser, Kathy Zyck, Eleuterio Ferrannini, and Ralph A. DeFronzo

Fourth Department of Medicine, Helsinki University Hospital, Finland.

Find articles by Groop, L. in: JCI | PubMed | Google Scholar

Fourth Department of Medicine, Helsinki University Hospital, Finland.

Find articles by Bonadonna, R. in: JCI | PubMed | Google Scholar

Fourth Department of Medicine, Helsinki University Hospital, Finland.

Find articles by DelPrato, S. in: JCI | PubMed | Google Scholar

Fourth Department of Medicine, Helsinki University Hospital, Finland.

Find articles by Ratheiser, K. in: JCI | PubMed | Google Scholar

Fourth Department of Medicine, Helsinki University Hospital, Finland.

Find articles by Zyck, K. in: JCI | PubMed | Google Scholar

Fourth Department of Medicine, Helsinki University Hospital, Finland.

Find articles by Ferrannini, E. in: JCI | PubMed | Google Scholar

Fourth Department of Medicine, Helsinki University Hospital, Finland.

Find articles by DeFronzo, R. in: JCI | PubMed | Google Scholar

Published July 1, 1989 - More info

Published in Volume 84, Issue 1 on July 1, 1989
J Clin Invest. 1989;84(1):205–213. https://doi.org/10.1172/JCI114142.
© 1989 The American Society for Clinical Investigation
Published July 1, 1989 - Version history
View PDF
Abstract

The effect of graded, physiologic hyperinsulinemia (+5, +15, +30, +70, +200 microU/ml) on oxidative and nonoxidative pathways of glucose and FFA metabolism was examined in nine lean non-insulin dependent diabetic patients (NIDDM) and in eight age- and weight-matched control subjects. Glucose and FFA metabolism were assessed using stepwise insulin clamp in combination with indirect calorimetry and infusion of [3H]3-glucose/[14C]palmitate. The basal rate of hepatic glucose production (HGP) was higher in NIDDM than in control subjects, and suppression of HGP by insulin was impaired at all but the highest insulin concentration. Glucose disposal was reduced in the NIDD patients at the three highest plasma insulin concentrations, and this was accounted for by defects in both glucose oxidation and nonoxidative glucose metabolism. In NIDDs, suppression of plasma FFA by insulin was impaired at all five insulin steps. This was associated with impaired suppression by insulin of plasma FFA turnover, FFA oxidation (measured by [14C]palmitate) and nonoxidative FFA disposal (an estimate of reesterification of FFA). FFA oxidation and net lipid oxidation (measured by indirect calorimetry) correlated positively with the rate of HGP in the basal state and during the insulin clamp. In conclusion, our findings demonstrate that insulin resistance is a general characteristic of glucose and FFA metabolism in NIDDM, and involves both oxidative and nonoxidative pathways. The data also demonstrate that FFA/lipid and glucose metabolism are interrelated in NIDDM, and suggest that an increased rate of FFA/lipid oxidation may contribute to the impaired suppression of HGP and diminished stimulation of glucose oxidation by insulin in these patients.

Browse pages

Click on an image below to see the page. View PDF of the complete article

icon of scanned page 205
page 205
icon of scanned page 206
page 206
icon of scanned page 207
page 207
icon of scanned page 208
page 208
icon of scanned page 209
page 209
icon of scanned page 210
page 210
icon of scanned page 211
page 211
icon of scanned page 212
page 212
icon of scanned page 213
page 213
Version history
  • Version 1 (July 1, 1989): Updated with full author names.

Article tools

  • View PDF
  • Download citation information
  • Send a comment
  • Terms of use
  • Standard abbreviations
  • Need help? Email the journal

Metrics

  • Article usage
  • Citations to this article

Go to

  • Top
  • Abstract
  • Version history
Advertisement
Advertisement

Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts