The international journal of biochemistry & cell biology
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Int. J. Biochem. Cell Biol. · Oct 1997
G proteins and regulation of pyruvate dehydrogenase activity by insulin in human circulating lymphocytes.
Pertussis toxin (PT) catalyzes ADP-ribosylation of G protein alpha subunits, thus preventing their role as transducers of external signals targeting metabolic pathways. In vitro, in human circulating lymphocytes insulin at physiological concentrations (5 microU/ml) determines sharp activation of pyruvate dehydrogenase (PDH), the rate limiting enzyme in glucose oxidative breakdown. This study evaluates whether the above-described effects of insulin over PDH are mediated through G proteins. ⋯ In circulating lymphocytes exposed to PT alone, or in combination with insulin, PDH activity falls significantly below basal values (P < 0.001); PT-9K instead has no effect on basal or on insulin-stimulated PDH activity. ADP-ribosylation of a plasma membrane component with apparent molecular mass (42 kDa) comparable to that of the Gi (inhibitory) protein alpha subunit takes place in cells exposed to PT but not in those exposed to PT-9K. In human circulating lymphocytes Gi proteins or Gi protein-like components appear to be involved in preserving basal PDH activity as well as in the mechanism by which insulin exerts its control over PDH.