G proteins and regulation of pyruvate dehydrogenase activity by insulin in human circulating lymphocytes
The International Journal of Biochemistry & Cell Biology, ISSN: 1357-2725, Vol: 29, Issue: 10, Page: 1207-1217
1997
- 10Citations
- 2Captures
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Metrics Details
- Citations10
- Citation Indexes10
- 10
- CrossRef5
- Captures2
- Readers2
Article Description
Pertussis toxin (PT) catalyzes ADP-ribosylation of G protein α subunits, thus preventing their role as transducers of external signals targeting metabolic pathways. In vitro, in human circulating lymphocytes insulin at physiological concentrations (5 μU/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. Human circulating lymphocytes (six samples from different donors) were exposed to insulin (5 μU/ml), PT (1–2 μg/ml) or PT-9K, a mutated PT void of catalytic activity (1–10 μg/ml), and to insulin in combination with the two toxins, and then assessed for PDH activity. Plasma membranes from cells incubated with and without PT or PT-9K were subjected to ADP-ribosylation in the presence of [ 32 P] NAD + and activated PT. 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 α 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.
Bibliographic Details
http://www.sciencedirect.com/science/article/pii/S1357272597000496; http://dx.doi.org/10.1016/s1357-2725(97)00049-6; http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=0030807779&origin=inward; http://www.ncbi.nlm.nih.gov/pubmed/9438382; http://linkinghub.elsevier.com/retrieve/pii/S1357272597000496; http://api.elsevier.com/content/article/PII:S1357272597000496?httpAccept=text/xml; http://api.elsevier.com/content/article/PII:S1357272597000496?httpAccept=text/plain; https://linkinghub.elsevier.com/retrieve/pii/S1357272597000496; http://dx.doi.org/10.1016/s1357-2725%2897%2900049-6; https://dx.doi.org/10.1016/s1357-2725%2897%2900049-6
Elsevier BV
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