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Insulin Binding to Monocytes and Insulin Action in Human Obesity, Starvation, and Refeeding
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Insulin binding to monocytes and insulin action in vivo was examined in 14 obese subjects during the postabsorptive state and after starvation and refeeding. Tissue sensitivity to insulin was evaluated with the euglycemic insulin clamp technique. The plasma insulin concentration is acutely raised and maintained 100 muU/ml above the fasting level, and plasma glucose is held constant by a variable glucose infusion. The amount of glucose infused is a measure of tissue sensitivity to insulin and averaged 285+/-15 mg/m(2) per min in controls compared to 136+/-13 mg/m(2) per min in obese subjects (P <0.001). (125)I-Insulin binding to monocytes averaged 8.3+/-0.4% in controls vs. 4.6+/-0.5% in obese subjects (P < 0.001). Insulin binding and insulin action were highly correlated in both control (r = 0.86, P < 0.001) and obese (r = 0.94, P < 0.001) groups. Studies employing tritiated glucose to measure glucose production indicated hepatic as well as extrahepatic resistance to insulin in obesity. After 3 and 14 days of starvation, insulin sensitivity in obese subjects decreased to 69+/-4 and 71+/-7 mg/m(2) per min, respectively, whereas (125)I-insulin binding increased to 8.8+/-0.7 and 9.0+/-0.4%. In contrast to the basal state, there was no correlation between insulin binding and insulin action. After refeeding, tissue sensitivity increased to 168+/-14 mg/m(2) per min (P < 0.001) whereas insulin binding fell to 5.0+/-0.3%. We conclude that (a) in the postabsorptive state insulin binding to monocytes provides an index of in vivo insulin action in nonobese and obese subjects and, (b) during starvation and refeeding, insulin binding and insulin action changes in opposite directions suggesting that postreceptor events determine in vivo insulin sensitivity.
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“Thus, our results are consistent with the diminished S of obese subjects elucidated by both qualitative (26) and quantitative techniques (25).”
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“Using the gold standard euglycemic hyperinsulinemic clamp technique to quantify insulin-stimulated glucose uptake, they demonstrated that both lean and obese T2DM subjects have marked decrease (>50%) in whole body glucose disposal during the insulin clamp.”
From Pathogenesis of insulin resistance in skeletal muscle (2010) · cites this paper as [28]
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“Both acute (4 hours) and chronic (4 days) physiologic elevation of plasma FFA concentration in insulin sensitive individuals impairs insulin signaling and causes insulin resistance in skeletal muscle [28, 62–68].”
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Metadata
- Authors
- Defronzo, R. A., Soman, V., Sherwin, R. S., Hendler, R., & Felig, P.
- Affiliations
- Yale University (US)
- ORCID
- Defronzo, Ralph A.
- Venue
- Journal of Clinical Investigation
- Published
- 1978-07-01
- Volume
- 62
- Issue
- 1
- Pages
- 204-213
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC371755
- OpenAlex
- W1969572070
- Cited by
- 252
- References
- 41
- Citations by year
- 2026: 1 · 2024: 4 · 2023: 3 · 2020: 1 · 2019: 2 · 2018: 3 · 2017: 3 · 2015: 2 · 2014: 4 · 2013: 3 · 2012: 5
- FWCI
- 33.28
- Type
- journal article
- Language
- en
- Status
- Retracted
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- American Diabetes Association
- National Institutes of Health (RR-00125)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pancreatic function and diabetes
- Keywords
- insulin binding, monocytes, insulin resistance, obesity, starvation, refeeding, postabsorptive state, insulin action, hepatic insulin resistance, hyperinsulinemic-euglycemic clamp, glucose production
- MeSH terms
- Adolescent, Adult, Eating, Female, Glucose, Humans, Insulin, Liver, Male, Middle Aged, Monocytes, Obesity, Starvation
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