Cited by 169Metabolism, Diabetes, and CancerAdipokines, Inflammation, and Metabolic DiseasesAdipose Tissue and Metabolism

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Role of glucose transporters in the cellular insulin resistance of type II non-insulin-dependent diabetes mellitus.

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Garvey, W T, Huecksteadt, T P, Matthaei, S, Olefsky, J M·1988·Journal of Clinical Investigation

DOI 10.1172/jci113485PMC PMC442586

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Abstract

To examine the role of glucose transport proteins in cellular insulin resistance, we studied subcutaneous adipocytes isolated from lean control, obese control (body mass index [BMI] 33.4 +/- 0.9), and untreated obese non-insulin-dependent diabetes mellitus (NIDDM) patients (BMI 35.2 +/- 2.1; fasting glucose 269 +/- 20 mg/dl). Glucose transporters were measured in plasma membrane (PM), low-density (LDM), and high-density (HDM) microsomal subfractions from basal and maximally insulin-stimulated cells using the cytochalasin B binding assay, and normalized per milligram of membrane protein. In all subgroups, insulin led to an increase in PM glucose transporters and a corresponding depletion of transporters in the LDM. Insulin recruited 20% fewer transporters to the PM in the obese subgroup when compared with lean controls, and this was associated with a decline in LDM transporters with enlarging cell size in the control subjects. In NIDDM, PM, and LDM, transporters were decreased 50% in both basal and stimulated cells when compared with obese controls having similar mean adipocyte size. Cellular depletion of glucose transporters was not the only cause of insulin resistance, because the decrease in rates of [14C]-D-glucose transport (basal and insulin-stimulated) was greater than could be explained by reduced numbers of PM transporters in both NIDDM and obesity. In HDM, the number of transporters was not influenced by insulin and was similar in all subgroups. We conclude that (a) in NIDDM and obesity, both reduced numbers and impaired activity of glucose transporters contribute to cellular insulin resistance, and (b) in NIDDM, more profound cellular insulin resistance is associated primarily with a further depletion of cellular transporters.

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Authors: Garvey, W. T., Huecksteadt, T. P., Matthaei, S., & Olefsky, J. M.
Affiliations: University of California San Diego (US)
United States Department of Veterans Affairs (US)
ORCID: Garvey, W T
Olefsky, J M
Venue: Journal of Clinical Investigation
Publisher: American Society for Clinical Investigation
Published: 1988-05-01
Volume: 81
Issue: 5
Pages: 1528-1536
ISSN: 0021-9738 (ISSN-L)
DOI: 10.1172/jci113485
PMC: PMC442586
OpenAlex: W2143122636
Cited by: 169
References: 42
Citations by year: 2025: 1 · 2024: 2 · 2023: 1 · 2022: 1 · 2021: 1 · 2020: 1 · 2019: 2 · 2018: 4 · 2017: 1 · 2016: 1 · 2015: 5 · 2014: 2 · 2013: 3
FWCI: 6.06
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: Journal of Clinical Investigation (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: Pfizer
Deutsche Forschungsgemeinschaft
National Institutes of Health (AM-33639, 2r01am033651-03)
National Center for Research Resources (RR00827)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
Health Sciences › Medicine › Physiology (medical) › Adipose Tissue and Metabolism
Keywords: glucose transporters, insulin resistance, type 2 diabetes, adipocytes, obesity, insulin-stimulated glucose transport, plasma membrane, low density microsomes, adipocyte size
MeSH terms: Adipose Tissue, Adult, Blood Glucose, Cell Membrane, Diabetes Mellitus, Diabetes Mellitus, Type 2, Female, Humans, Insulin Resistance, Male, Microsomes, Monosaccharide Transport Proteins, Obesity

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Role of glucose transporters in the cellular insulin resistance of type II non-insulin-dependent diabetes mellitus.

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