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Glucose transport in cultured human skeletal muscle cells. Regulation by insulin and glucose in nondiabetic and non-insulin-dependent diabetes mellitus subjects
Open accessAbstract
A primary human skeletal muscle culture (HSMC) system, which retains cellular integrity and insulin responsiveness for glucose transport was employed to evaluate glucose transport regulation. As previously reported, cells cultured from non-insulin-dependent diabetic (NIDDM) subjects displayed significant reductions in both basal and acute insulin-stimulated transport compared to nondiabetic controls (NC). Fusion/differentiation of NC and NIDDM HSMC in elevated media insulin (from 22 pM to 30 microM) resulted in increased basal transport activities but reduced insulin-stimulated transport, so that cells were no longer insulin responsive. After fusion under hyperinsulinemic conditions, GLUT1 protein expression was elevated in both groups while GLUT4 protein level was unaltered. Fusion of HSMC under hyperglycemic conditions (10 and 20 mM) decreased glucose transport in NC cells only when combined with hyperinsulinemia. Hyperglycemia alone down-regulated transport in HSMC of NIDDM, while the combination of hyperglycemia and hyperinsulinemia had greater effects. In summary: (a) insulin resistance of glucose transport can be induced in HSMC of both NC and NIDDM by hyperinsulinemia and is accompanied by unaltered GLUT4 but increased GLUT1 levels; and (b) HSMC from NIDDM subjects demonstrate an increased sensitivity to impairment of glucose transport by hyperglycemia. These results indicate that insulin resistance in skeletal muscle can be acquired in NC and NIDDM from hyperinsulinemia alone but that NIDDM is uniquely sensitive to the additional influence of hyperglycemia.
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“Insulin-mediated translocation of GLUT4 to the muscle sarcolemmal membrane was impaired in patients with type 2 diabetes mellitus.24,25”
From Lipid-induced insulin resistance: unravelling the mechanism (2010) · cites this paper as [24]
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Metadata
- Authors
- Ciaraldi, T. P., Abrams, L., Nikoulina, S., Mudaliar, S., & Henry, R. R.
- Affiliations
- Veterans Health Administration (US)
- Venue
- Journal of Clinical Investigation
- Published
- 1995-12-01
- Volume
- 96
- Issue
- 6
- Pages
- 2820-2827
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC185992
- OpenAlex
- W2060118222
- Cited by
- 124
- References
- 50
- Citations by year
- 2025: 2 · 2024: 1 · 2023: 4 · 2022: 3 · 2021: 5 · 2020: 3 · 2019: 4 · 2018: 3 · 2017: 3 · 2016: 3 · 2015: 4 · 2014: 3 · 2013: 7 · 2012: 9
- FWCI
- 0.86
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- American Diabetes Association
- U.S. Department of Veterans Affairs
- American Heart Association
- National Institutes of Health (5r29dk038949-05)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK 38949)
- National Center for Research Resources (MO1 RR00827, M01RR000827)
- 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 (medical) › Adipose Tissue and Metabolism
- Keywords
- glucose transport, skeletal muscle cells, insulin resistance, type 2 diabetes, hyperinsulinemia, hyperglycemia, GLUT1, GLUT4, insulin-stimulated glucose transport, cell fusion
- MeSH terms
- Adult, Biopsy, Cell Differentiation, Cell Fusion, Cell Membrane, Cells, Cultured, Diabetes Mellitus, Type 2, Glucose, Humans, Hyperglycemia, Hyperinsulinism, Insulin, Middle Aged, Monosaccharide Transport Proteins, Muscle Proteins, Reference Values, Muscle, Skeletal, Glucose Transporter Type 1, Glucose Transporter Type 4
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