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Cited by 175Diabetes, Cardiovascular Risks, and LipoproteinsPancreatic function and diabetesMetabolism, Diabetes, and Cancer

Characterization of cellular defects of insulin action in type 2 (non-insulin-dependent) diabetes mellitus.

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Del Prato, S, Bonadonna, R C, Bonora, E, Gulli, G, Solini, A, Shank, M, DeFronzo, R A·1993·Journal of Clinical Investigation
DOI 10.1172/jci116226PMC PMC287962
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Abstract

Seven non-insulin-dependent diabetes mellitus (NIDDM) patients participated in three clamp studies performed with [3-3H]- and [U-14C]glucose and indirect calorimetry: study I, euglycemic (5.2 +/- 0.1 mM) insulin (269 +/- 39 pM) clamp; study II, hyperglycemic (14.9 +/- 1.2 mM) insulin (259 +/- 19 pM) clamp; study III, euglycemic (5.5 +/- 0.3 mM) hyperinsulinemic (1650 +/- 529 pM) clamp. Seven control subjects received a euglycemic (5.1 +/- 0.2 mM) insulin (258 +/- 24 pM) clamp. Glycolysis and glucose oxidation were quantitated from the rate of appearance of 3H2O and 14CO2; glycogen synthesis was calculated as the difference between body glucose disposal and glycolysis. In study I, glucose uptake was decreased by 54% in NIDDM vs. controls. Glycolysis, glycogen synthesis, and glucose oxidation were reduced in NIDDM patients (P < 0.05-0.001). Nonoxidative glycolysis and lipid oxidation were higher. In studies II and III, glucose uptake in NIDDM was equal to controls (40.7 +/- 2.1 and 40.7 +/- 1.7 mumol/min.kg fat-free mass, respectively). In study II, glycolysis, but not glucose oxidation, was normal (P < 0.01 vs. controls). Nonoxidative glycolysis remained higher (P < 0.05). Glycogen deposition increased (P < 0.05 vs. study I), and lipid oxidation remained higher (P < 0.01). In study III, hyperinsulinemia normalized glycogen formation, glycolysis, and lipid oxidation but did not normalize the elevated nonoxidative glycolysis or the decreased glucose oxidation. Lipid oxidation and glycolysis (r = -0.65; P < 0.01), and glucose oxidation (r = -0.75; P < 0.01) were inversely correlated. In conclusion, in NIDDM: (a) insulin resistance involves glycolysis, glycogen synthesis, and glucose oxidation; (b) hyperglycemia and hyperinsulinemia can normalize total body glucose uptake; (c) marked hyperinsulinemia normalizes glycogen synthesis and total flux through glycolysis, but does not restore a normal distribution between oxidation and nonoxidative glycolysis; (d) hyperglycemia cannot overcome the defects in glucose oxidation and nonoxidative glycolysis; (e) lipid oxidation is elevated and is suppressed only with hyperinsulinemia.

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  • In type 2 diabetic individuals, the glycolytic/glucose oxidative pathway has been shown to be impaired.

    “In type 2 diabetic individuals, the glycolytic/glucose oxidative pathway has been shown to be impaired [229].”

    From Pathogenesis of insulin resistance in skeletal muscle (2010) · cites this paper as [229]

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Research works printed but not linked: 2

  1. Ferrannini, E., S. Del Prato, and R. A. De Fronzo. 1986. Glucose kinetics: tracer techniques. In Methods in Diabetes Research. Volume II. W. Z. Clarke, J. Larner, and S. L. Pohl, editors. John Wiley & Son, Inc., New York. 107-142.
  2. Hohorst, H.-J. 1965. L-(+)-lactate: determination with lactic dehydroge- nase and DPN. In Methods of Enzymatic Analysis. H.-V. Bergmeyer, editor. Academic Press, Inc., New York. 266-270.

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Authors
Del Prato, S., Bonadonna, R. C., Bonora, E., Gulli, G., Solini, A., Shank, M., & DeFronzo, R. A.
Affiliations
University of Padua (IT)
ORCID
Venue
Journal of Clinical Investigation
Publisher
American Society for Clinical Investigation
Published
1993-02-01
Volume
91
Issue
2
Pages
484-494
ISSN
0021-9738 (ISSN-L)
DOI
10.1172/jci116226
PMC
PMC287962
OpenAlex
W2158104654
Cited by
170
References
51
Citations by year
2026: 2 · 2025: 1 · 2024: 6 · 2022: 5 · 2021: 3 · 2020: 5 · 2019: 2 · 2018: 11 · 2017: 4 · 2016: 3 · 2015: 7 · 2014: 7 · 2013: 6 · 2012: 2
FWCI
6.32
Type
journal article
Language
en
Open access
Locations
  • Journal of Clinical Investigation (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • CINECA IRIS Institutial research information system (University of Pisa) (submittedVersion)
Funders
  • American Diabetes Association
  • Università degli Studi di Padova
  • National Institutes of Health
  • National Institute of Diabetes and Digestive and Kidney Diseases (DK 24092)
  • National Center for Research Resources (M01-RR-013436)
  • NIH Clinical Center
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
  • Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
Keywords
type 2 diabetes, insulin resistance, insulin action, glucose uptake, glycolysis, glucose oxidation, glycogen synthesis, lipid oxidation, hyperinsulinemic-euglycemic clamp, hyperglycemic clamp, glucose disposal, skeletal muscle metabolism, glycogen accumulation, nonoxidative glucose metabolism
MeSH terms
Adult, Diabetes Mellitus, Type 2, Fatty Acids, Nonesterified, Female, Glucose, Glycogen, Glycolysis, Humans, Insulin, Lactates, Liver, Male, Middle Aged, Oxidation-Reduction, Lactic Acid, Lipid Metabolism

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