Insulin signal transduction and glucose transport in human adipocytes: effects of obesity and low calorie diet
Open accessAbstract
Aim/hypothesis We examined insulin signal transduction at the level of insulin receptor substrates (IRS) 1 and 2, phosphatidylinositol (PI) 3-kinase and glucose transport in isolated subcutaneous adipocytes from obese and lean women.Methods Glucose transport and insulin signalling were investigated in isolated adipocytes from six obese women (BMI 36-43 kg/m(2)) (before and after 11 days of very low calorie diet) and from six lean women (BMI 22-26 kg/m(2)).Results Insulin sensitivity of glucose transport was reduced in adipocytes from obese women (p<0.05), with further reductions in basal and maximal insulin-stimulated glucose transport after a very low calorie diet (p<0.05). In obese women, IRS-1 associated PI 3-kinase activity was markedly impaired (p<0.05), whereas, IRS-2 associated PI 3-kinase activity was normal. IRS-1 associated PI 3-kinase activity remained blunted after a very low calorie diet, whereas IRS-2 associated PI 3-kinase activity was increased. GLUT4 protein was reduced by 37% in obese versus lean subjects (p<0.05), and decreased further after a very low calorie diet (from 19+/-4 to 14+/-4 arbitrary units; p<0.05).Conclusion/interpretation IRS-1 signalling to PI 3-kinase is a site of insulin resistance in adipocytes from obese women, whereas insulin action on IRS-2 is normal. Thus, IRS-1 and IRS-2 undergo differential regulation in adipocytes from obese insulin resistant subjects. Finally, a very low calorie diet is associated with a further impairment in glucose transport in adipose tissue. The defect in glucose transport after a very low calorie diet occurs independent of further defects in insulin signalling at the level of the PI 3-kinase.
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The finding challenges the belief that sleep primarily restores central nervous system function and suggests that sleep may play an equally important role in peripheral energy metabolism.
“Further, our finding of marked alterations in adipocyte function after experimental sleep restriction challenges the widely held belief that the primary function of sleep is the restoration of central nervous system function (26–29) and suggests that sleep may play an equally important role in peripheral energy metabolism.”
From Impaired Insulin Signaling in Human Adipocytes After Experimental Sleep Restriction: A Randomized, Crossover Study (2012) · cites this paper as [29]
The Abstract and Discussion (page numbers unavailable) address insulin signalling and glucose transport in adipocytes from obese women, not sleep. Searches for sleep restriction and restoration of central nervous system function found no passage addressing the belief to which the citation is attached. (LLM, conf=0.75)
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- Authors
- M., B., L., A.-K., A., D., E., N., S., R., J., Z., & P., A.
- Venue
- Diabetologia
- Published
- 2002-08-01
- Volume
- 45
- Issue
- 8
- Pages
- 1128-1135
- ISSN
- 0012-186X (ISSN-L)
- 1432-0428
- OpenAlex
- W2042168071
- Cited by
- 28
- References
- 32
- Citations by year
- 2022: 1 · 2020: 2 · 2017: 1 · 2015: 2 · 2014: 1 · 2013: 1 · 2012: 1
- FWCI
- 2.01
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Diabetologia (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Novo Nordisk
- Medical Research Council
- Strategic Research Council
- Topics
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Keywords
- insulin signaling, glucose transport, adipocytes, obesity, very low calorie diet, insulin resistance, IRS-1, insulin receptor substrate 2, phosphatidylinositol 3-kinase, GLUT4, subcutaneous adipose tissue, women
- MeSH terms
- Adult, Biological Transport, Energy Intake, Cell Extracts, Female, Glucose, Humans, Insulin, Middle Aged, Obesity, Osmolar Concentration, Phosphoproteins, Proteins, Signal Transduction, Adipocytes, Phosphatidylinositol 3-Kinases, Intracellular Signaling Peptides and Proteins, Insulin Receptor Substrate Proteins
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