Cited by 234Metabolism, Diabetes, and CancerAdipokines, Inflammation, and Metabolic DiseasesDiabetes, Cardiovascular Risks, and Lipoproteins

Decreased kinase activity of insulin receptors from adipocytes of non-insulin-dependent diabetic subjects.

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Freidenberg, G R, Henry, R R, Klein, H H, Reichart, D R, Olefsky, J M·1987·Journal of Clinical Investigation

Abstract

The tyrosine kinase activity of the insulin receptor was examined with partially-purified insulin receptors from adipocytes obtained from 13 lean nondiabetics, 14 obese nondiabetics, and 13 obese subjects with non-insulin-dependent diabetes (NIDDM). Incubation of receptors at 4 degrees C with [gamma-32P]ATP and insulin resulted in a maximal 10-12-fold increase in autophosphorylation of the 92-kDa beta-subunit of the receptor with a half maximal effect at 1-3 ng/ml free insulin. Insulin receptor kinase activity in the three experimental groups was measured by means of both autophosphorylation and phosphorylation of the exogenous substrate Glu4:Tyr1. In the absence of insulin, autophosphorylation and Glu4:Tyr1 phosphorylation activities, measured with equal numbers of insulin receptors, were comparable among the three groups. In contrast, insulin-stimulated kinase activity was comparable in the control and obese subjects, but was reduced by approximately 50% in the NIDDM group. These findings indicate that the decrease in kinase activity in NIDDM resulted from a reduction in coupling efficiency between insulin binding and activation of the receptor kinase. The insulin receptor kinase defects observed in NIDDM could be etiologically related to insulin resistance in NIDDM and the pathogenesis of the diabetic state.

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Crossref · 10.1172/jci112789

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  • Early studies found a modest 20-30% reduction in insulin binding to monocytes and adipocytes from type 2 diabetic patients, but this was not a consistent finding.

    “Early studies have demonstrated a modest 20–30% reduction in insulin binding to monocytes and adipocytes from type 2 diabetic patients, but this has not been a consistent finding [1, 151–154].”

    From Pathogenesis of insulin resistance in skeletal muscle (2010) · cites this paper as [151]

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Authors
Freidenberg, G. R., Henry, R. R., Klein, H. H., Reichart, D. R., & Olefsky, J. M.
Affiliations
United States Department of Veterans Affairs (US)
Venue
Journal of Clinical Investigation
Published
1987-01-01
Volume
79
Issue
1
Pages
240-250
ISSN
0021-9738 (ISSN-L)
OpenAlex
W2169226001
Cited by
234
References
58
Citations by year
2026: 1 · 2024: 1 · 2023: 1 · 2022: 1 · 2021: 2 · 2020: 1 · 2019: 1 · 2018: 4 · 2017: 2 · 2016: 1 · 2015: 4 · 2014: 4 · 2013: 1 · 2012: 1
FWCI
11.43
Type
journal article
Language
en
Open access
Locations
  • Journal of Clinical Investigation (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Institutes of Health (AM 33650, 2r01am033651-03, AM-07494)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
  • Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
Keywords
insulin receptor, tyrosine kinase activity, type 2 diabetes, insulin resistance, adipocytes, receptor autophosphorylation, obesity, insulin binding
MeSH terms
Adipose Tissue, Diabetes Mellitus, Type 2, Humans, Insulin, Obesity, Phosphorylation, Protein-Tyrosine Kinases, Receptor, Insulin, Substrate Specificity

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