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Influence of a small molecular weight proteinase inhibitor, gabexate mesilate (FOY), on insulin receptor function in
R Göke1, B Göke, H J Steinfelder
1Institute of Pharmacology and Toxicology, University of Göttingen, F.R.G.
Abstract:
The effects of the low molecular weight serine proteinase inhibitor FOY (gabexate mesilate) upon insulin action was studied in three different experimental systems. Placenta membranes containing insulin receptors preincubated with FOY (10 microM) showed a reduction of insulin-stimulated tyrosine kinase activity (p less than 0.01). However, FOY (0.1-100 microM) did not affect the insulin-stimulated tyrosine kinase activity in a preparation of solubilized and partially purified insulin receptors from placental membranes. Isolated adipocytes were used to study the effect of FOY on intact cells. FOY neither altered the insulin induced inhibition of the catecholamine-stimulated lipolysis nor (at the low concentration of 0.1 mM) the stimulation of glucose transport by the hormone. High concentrations (0.5 mM) of FOY decreased the effect of insulin on the hexose transport.
Insights
The serine proteinase inhibitor FOY (gabexate mesilate) partially impairs insulin receptor function. High concentrations of FOY reduced insulin
Area of Science:
- Biochemistry
- Pharmacology
- Endocrinology
Background:
- Insulin action is crucial for glucose homeostasis.
- Serine proteinase inhibitors can modulate cellular signaling pathways.
- FOY (gabexate mesilate) is a low molecular weight serine proteinase inhibitor.
Purpose of the Study:
- To investigate the effects of FOY on insulin action.
- To determine if FOY affects insulin receptor tyrosine kinase activity.
- To assess FOY's impact on insulin-mediated cellular responses in adipocytes.
Main Methods:
- Insulin receptor tyrosine kinase activity assays using placental membranes.
- Enzyme activity assays with solubilized and partially purified insulin receptors.
- Studies on isolated adipocytes to measure lipolysis and glucose transport.
Main Results:
- FOY (10 microM) reduced insulin-stimulated tyrosine kinase activity in placental membranes (p < 0.01).
- FOY (0.1-100 microM) did not affect tyrosine kinase activity in solubilized receptors.
- FOY did not alter insulin's effect on lipolysis or glucose transport at low concentrations (0.1 mM).
- High FOY concentrations (0.5 mM) diminished insulin's effect on hexose transport in adipocytes.
Conclusions:
- FOY exhibits differential effects on insulin receptor activity depending on the preparation.
- FOY may interfere with insulin signaling in intact cells at higher concentrations.
- Further research is needed to elucidate the precise mechanisms of FOY's interaction with insulin action.