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Taboada GF, de Freitas MS, da S Corrêa FH, et al. Insulin signaling pathways in a patient with insulin resistance of difficult management - a case report. Diabetol Metab Syndr. 2009;1(1):23doi: 10.1186/1758-5996-1-23.
Taboada, G. F., de Freitas, M. S., da S Corrêa, F. H., Junior, C. R., & de B Gomes, M. (2009). Insulin signaling pathways in a patient with insulin resistance of difficult management - a case report. Diabetology & metabolic syndrome, 1(1), 23. https://doi.org/10.1186/1758-5996-1-23
Taboada, Giselle F, et al. "Insulin signaling pathways in a patient with insulin resistance of difficult management - a case report." Diabetology & metabolic syndrome vol. 1,1 (2009): 23. doi: https://doi.org/10.1186/1758-5996-1-23
Taboada GF, de Freitas MS, da S Corrêa FH, Junior CR, de B Gomes M. Insulin signaling pathways in a patient with insulin resistance of difficult management - a case report. Diabetol Metab Syndr. 2009 Nov 26;1(1):23. doi: 10.1186/1758-5996-1-23. PMID: 19941665; PMCID: PMC2789034.
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Diabetol Metab Syndr. 2009 Nov 26;1(1):23. doi: 10.1186/1758-5996-1-23.

Insulin signaling pathways in a patient with insulin resistance of difficult management - a case report.

Diabetology & metabolic syndrome

Giselle F Taboada, Marta S de Freitas, Fernanda H da S Corrêa, Carlos Rma Junior, Marília de B Gomes

Affiliations

  1. Diabetes & Metabology Unit, Internal Medicine Department, State University of Rio de Janeiro, Rio de Janeiro, Brazil. [email protected].

PMID: 19941665 PMCID: PMC2789034 DOI: 10.1186/1758-5996-1-23

Abstract

Insulin signalling pathways were investigated in a 33 year-old woman with immunologic insulin resistance. Her past medical history was remarkable for intermittent use of insulin and allergic reactions to several drugs, and measure of plasma anti-insulin antibodies level corroborated the clinical suspicion of immune mediated insulin resistance (8074 nU/ml - RIA - Ref value: <60). Treatment with several immunosuppressive regimens was tried, however the results were disappointing. Possible subcellular mechanisms of insulin resistance were investigated by performing analysis of insulin receptor and post receptor signaling in skeletal muscle biopsy. The expression of insulin receptor (IR), insulin receptor substrate 1 (IRS-1) and glucose transporter 4 (GLUT-4) was evaluated in total extract from muscle tissue by Western blotting. Basal IR, IRS-1 and GLUT-4 expression was detected, however receptor autophosphorylation was not observed. A study of translocation of GLUT-4 to plasma membrane showed that tissue presented low levels of membrane-associated GLUT-4. When in vitro stimulation was undertaken, tissue was capable to be responsive to insulin. Our results suggest that even though IR expression was normally occurring, IR beta-subunit tyrosine kinase activity in muscle was down-regulated leading to alterations in insulin post receptor signaling. Consistent with normal insulin receptor and post receptor signaling, our results were compatible with decreased insulin binding to IR probably due to neutralization by anti-insulin antibodies. In conclusion, this patient has immunologic insulin resistance and treatment should be based on immunosuppressive drugs as tolerated.

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