TY - JOUR
T1 - Protein tyrosine phosphatase regulation in fibroblasts from patients with an insulin receptor gene mutation
AU - Seki, N.
AU - Yagi, S.
AU - Suzuki, Y.
AU - Shimada, F.
AU - Taira, M.
AU - Makino, H.
AU - Amano, K.
AU - Yagui, K.
AU - Saito, Y.
AU - Hashimoto, N.
PY - 2008/12
Y1 - 2008/12
N2 - 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.
AB - 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.
KW - Diabetes mellitus
KW - Insulin resistance
KW - Leukocyte antigen-related PTPase
KW - Protein tyrosine phosphatase 1B
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U2 - 10.1055/s-0028-1082082
DO - 10.1055/s-0028-1082082
M3 - Article
C2 - 18925540
AN - SCOPUS:58149125247
VL - 40
SP - 833
EP - 837
JO - Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et métabolisme
JF - Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et métabolisme
SN - 0018-5043
IS - 12
ER -