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High glucose-induced abnormal epidermal growth factor signaling
T Obata1, H Maegawa, A Kashiwagi
1Third Department of Medicine, Shiga University of Medical Science, Seta, Otsu, Shiga 520-2192, Japan.
Journal of Biochemistry
|June 19, 1998
Summary
High glucose increases protein tyrosine phosphatase 1B (PTP1B) and leukocyte common antigen-related phosphatase (LAR) in fibroblasts, impairing insulin signaling. Pioglitazone reduces PTP1B, improving insulin signaling but not epidermal growth factor (EGF) signaling.
Area of Science:
- Biochemistry
- Cell Biology
- Endocrinology
Background:
- High glucose conditions impair insulin signaling through protein tyrosine phosphatases (PTPases).
- Previous work showed PTPase activation under high glucose in Rat 1 fibroblasts.
- This study investigates specific PTPases and their response to high glucose and pioglitazone.
Purpose of the Study:
- To examine the effects of high glucose on specific PTPase mRNA and protein levels.
- To investigate the impact of pioglitazone on PTPase activity and signaling pathways.
- To determine the role of increased cytosolic PTP1B in high glucose-induced EGF receptor dysfunction.
Main Methods:
- Cultured Rat 1 fibroblasts under high glucose (27 mM) conditions.
- Quantification of PTPase mRNA and protein levels (PTP1B, LAR, LRP).
- Assessed effects of pioglitazone on PTPase activity and EGF-stimulated signaling.
Main Results:
- High glucose increased mRNA for PTP1B, LAR, and LRP; LAR protein was elevated.
- Cytosolic PTP1B increased, while membrane-associated PTP1B remained unchanged.
- Pioglitazone reduced cytosolic PTP1B and normalized PTPase activity but did not affect EGF signaling.
Conclusions:
- High glucose dysregulates EGF receptor signaling independently of increased cytosolic PTP1B.
- Increased cytosolic PTP1B contributes to impaired insulin signaling under high glucose.
- Pioglitazone ameliorates high glucose-induced insulin signaling defects by reducing cytosolic PTP1B.