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Polyamines as mediators of insulin's action on pyruvate dehydrogenase, /sup 45/Ca/sup 2 +/ fluxes, and membrane transport

Conference · · Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States)
OSTI ID:6832102
Insulin (IN) induces a rapid stimulation of Ca/sup 2 +/ fluxes and membrane transport in mouse kidney cortex which involves rapid polyamine synthesis. 1.3 nM (IN) induced an early (<30 sec) stimulation of pyruvate dehydrogenase (PDH) activity which peaked at 2 min (1.5-fold) followed by a significant decline (-31%) below basal between 5 and 10 min. IN induced a similar biphasic effect on membrane transport, with stimulation of ..cap alpha..-aminoisobutarate, 2-deoxyglucose and horseradish peroxidase transport peaking at 1 min, and decreasing below basal at 5-10 min. IN stimulation of ornithine decarboxylase (ODC) activity, polyamine accumulation and /sup 45/Ca/sup 2 +/ influx and efflux peaked at 1-2 min and returned to basal levels by 5-10 min. The ODC inhibitor ..cap alpha..-difluoromethylornithine (DFMO, 5 mM) abolished IN stimulation of PDH, /sup 45/Ca/sup 2 +/ fluxes and membrane transport, and putrescine (.5 mM) nullified DFMO inhibition. IN (50 mUnits/kg) in rats induced an early (< 1 min), coordinate increase in liver polyamine levels and PDH activity which peaked at 6 min and then declined. These effects were blocked by DFMO (200 mg/kg), and putrescine (100 mg/kg) negated DFMO inhibition. These results indicate that newly synthesized polyamines mediate IN's effects on PDH activity, Ca/sup 2 +/ fluxes, and membrane transport.
Research Organization:
Northwestern Univ. Medical School, Chicago, IL
OSTI ID:
6832102
Report Number(s):
CONF-8604222-
Conference Information:
Journal Name: Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States) Journal Volume: 45:4
Country of Publication:
United States
Language:
English