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Cited by 33Metabolism, Diabetes, and CancerDiabetes, Cardiovascular Risks, and LipoproteinsAdipose Tissue and Metabolism

Intracellular skeletal muscle glucose metabolism is differentially altered by dexamethasone treatment of normoglycemic relatives of type 2 diabetic patients

Henriksen, J.E., Alford, F., Vaag, A., Handberg, A., Beck-Nielsen, H.·1999·Metabolism
DOI 10.1016/s0026-0495(99)90126-9
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Abstract

Young first-degree relatives of type 2 diabetic patients are insulin-resistant, with the insulin resistance mainly located in skeletal muscle due to decreased insulin-induced nonoxidative glucose metabolism and muscle glycogen synthase activation. We investigated whether the mechanism differs for dexamethasone (dex)-induced insulin resistance in first-degree relatives of type 2 diabetics versus healthy control subjects by quantifying intracellular glucose processing in muscle biopsies taken before and after 5 days of dex treatment (4 mg/d) in 20 normal glucose-tolerant relatives of type 2 diabetic patients and 20 matched controls (age, 29.4 +/- 1.7 v 29.4 +/- 1.6 years; body mass index, 25.1 +/- 1.0 v 25.1 +/- 0.9 kg/m2). In addition, an intravenous glucose tolerance test (IVGTT) combined with continuous indirect calorimetry was performed. Following 5 days of dex treatment, glucose tolerance deteriorated in both the relatives and the control subjects. Fasting dry-weight muscle glucose and fasting intracellular muscle glucose concentrations increased in response to dex only in the relatives (2.43 +/- 0.21 v 2.97 +/- 0.26 mmol/kg dry weight, P < .05; 0.28 +/- 0.07 v 0.45 +/- 0.08 mmol/L intracellular water, P < .05); no increases were observed in the control subjects. Fasting dry-weight muscle lactate also increased post-dex only in the relatives (7.37 +/- 0.40 v 10.77 +/- 1.22 mmol/kg dry weight, P < .001). Both basal muscle glucose and lactate concentrations from the IVGTT study correlated with the 2-hour post-dex glucose value obtained during the OGTT study in the relatives (R = .76 and R = .74, respectively, both P < .0001) but not in the control subjects. Basal intramuscular glycogen synthase activity decreased approximately 25% in both the relatives and control subjects post-dex; the decrement was significant (P < .01) only in control subjects. Indirect calorimetry during the post-dex IVGTT demonstrated increased glucose oxidation (P < .03) and reduced lipid oxidation (P < .03) in the relatives only. We postulate that the insulin resistance induced by dex in first-degree relatives of type 2 diabetic patients is associated with a preferential channeling of glucose into the glycolytic pathway (increased glucose oxidation and lactate production), probably associated with a preexisting downregulation of the glycosen synthase pathway.

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Authors
Henriksen, J. E., Alford, F., Vaag, A., Handberg, A., & Beck-Nielsen, H.
Affiliations
University of Copenhagen (DK)
ORCID
Venue
Metabolism
Publisher
Elsevier BV
Published
1999-09
Volume
48
Issue
9
Pages
1128-1135
ISSN
0026-0495 (ISSN-L)
DOI
10.1016/s0026-0495(99)90126-9
OpenAlex
W1980235219
Cited by
33
References
46
Citations by year
2025: 1 · 2022: 1 · 2020: 1 · 2019: 3 · 2018: 3 · 2016: 2 · 2014: 2 · 2013: 8
FWCI
0.00
Type
journal article
Language
en
Open access
closed
Licence
Locations
  • Metabolism (publishedVersion)
  • PubMed (publishedVersion)
  • University of Southern Denmark Research Portal (University of Southern Denmark) (submittedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
  • Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
Keywords
dexamethasone, insulin resistance, type 2 diabetes, first-degree relatives, skeletal muscle glucose metabolism, intracellular glucose, glycogen synthase, glucose oxidation, lipid oxidation, lactate, glucose tolerance, glucocorticoids, muscle biopsy, indirect calorimetry, intravenous glucose tolerance test, nonoxidative glucose metabolism
MeSH terms
Adult, Dexamethasone, Diabetes Mellitus, Type 2, Female, Glucose, Glucose Tolerance Test, Glycogen, Glycogen Synthase, Humans, Insulin Resistance, Lipids, Male, Monosaccharide Transport Proteins, Muscle Proteins, Pedigree, Body Mass Index, Case-Control Studies, Muscle, Skeletal, Glucose-6-Phosphate, Lactic Acid, Glucose Transporter Type 4

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