RGD Reference Report - Protein tyrosine phosphatase regulation in fibroblasts from patients with an insulin receptor gene mutation. - Rat Genome Database

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Protein tyrosine phosphatase regulation in fibroblasts from patients with an insulin receptor gene mutation.

Authors: Seki, N  Yagi, S  Suzuki, Y  Shimada, F  Taira, M  Makino, H  Amano, K  Yagui, K  Saito, Y  Hashimoto, N 
Citation: Seki N, etal., Horm Metab Res. 2008 Dec;40(12):833-7. Epub 2008 Oct 16.
RGD ID: 2307343
Pubmed: PMID:18925540   (View Abstract at PubMed)
DOI: DOI:10.1055/s-0028-1082082   (Journal Full-text)

Tyrosine phosphorylation of the insulin receptor is the initial event following receptor binding to insulin, and it induces further tyrosine phosphorylation of various intracellular molecules. This signaling is countered by protein tyrosine phosphatases (PTPases), which reportedly are associated with insulin resistance that can be reduced by regulation of PTPases. Protein tyrosine phosphatase 1B (PTP1B) and leukocyte antigen-related PTPase (LAR) are the PTPases implicated most frequently in insulin resistance and diabetes mellitus. Here, we show that PTP1B and LAR are expressed in human fibroblasts, and we examine the regulation of PTPase activity in fibroblasts from patients with an insulin receptor gene mutation as an in vitro model of insulin resistance. Total PTPase activity was significantly lower in the cytosolic and membrane fractions of fibroblasts with mutations compared with controls (p<0.05). Insulin stimulation of fibroblasts with mutations resulted in a significantly smaller increase in PTP1B activity compared with stimulation of wild-type fibroblasts (p<0.05). This indicates that insulin receptor gene mutations blunt increases in PTPase activity in response to insulin, possibly via a negative feedback mechanism. Our data suggest that the PTPase activity in patients with insulin receptor gene mutation and severe insulin resistance may differ from that in ordinary type 2 diabetes.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
diabetes mellitus  IAGP 2307343DNA:deletions and missense mutation:multiple (human)RGD 
diabetes mellitus  ISOINSR (Homo sapiens)2307343; 2307343DNA:deletions and missense mutation:multiple (human)RGD 

Objects Annotated

Genes (Rattus norvegicus)
Insr  (insulin receptor)

Genes (Mus musculus)
Insr  (insulin receptor)

Genes (Homo sapiens)
INSR  (insulin receptor)


Additional Information