Insulin signaling pathways in a patient with insulin resistance of difficult management - a case report
Insulin signaling 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 determination of plasmatic anti-insulin antibodies corroborated the clinical suspicion of immune mediated insulin resistance (8074 nU/ml - RIA - Ref value: <60).
Treatment with several immunossupressive regimens was tried but the results were disappointing. Possible subcellular mechanisms of insulin resistance were investigated by performing a skeletal muscle biopsy.
The expression of insulin receptor (IR), IRS-1 and GLUT-4 was evaluated in total extract from muscle tissue by Western blotting. IR, IRS-1 and GLUT-4 immunocontent did not present marked alterations.
However, when IRS-1 protein content associated to membrane and IR tyrosine phosphorylation were analyzed, no IR activity was observed, despite the expressive subcellular localization. Also, tissue presented low levels of membrane-associated GLUT-4.
When in vitro stimulation was undertaken, tissue was showed to be responsive to insulin. Our results evidenced that even though IR expression was normally occuring, IR tyrosine kinase activity of muscle receptor beta-subunit was down-regulated consequently decreasing GLUT-4 translocation, despite its normal expression in muscle.
These findings were compatiblewith decreased insulin binding to IR, probably because of sequestration by anti-insulin antibodies. In conclusion, this patient has immunologic insulin resistance and treatment should be based on immunosuppressive drugs as tolerated.
Author: Giselle TaboadaMartha de FreitasFernanda CorreaCarlos AndradeMarilia Gomes
Credits/Source: Diabetology &Metabolic Syndrome 2009, 1:23
Published on: 2009-11-27
Copyright by the authors listed above - made available via BioMedCentral (Open Access). Please
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