The alpha-subunits of Gi and Gs were quantified in adipocyte membranes from young (2-month) and older (18-month) rats by pertussis-toxin and cholera-toxin labelling respectively. Aging was associated with a 3-fold increase in Gi alpha-subunit, but only a 2-fold increase in one of the two Gs alpha-subunit species labelled. The findings may explain the altered sensitivity of adipocytes from aged rats to lipolytic and anti-lipolytic stimuli.
To determine whether adenosine is involved in long-term regulation of glucose transport in adipose tissue, we have investigated effects of administration of an adenosine receptor antagonist (theophylline) on adipocyte glucose transport. Rats were injected with theophylline (30 mg/kg, dissolved in 0.9% NaCl) daily for 7 days. Controls were injected with saline. The rats were then killed, and epididymal adipocytes were isolated. Insulin-stimulated glucose transport rates were decreased by about 25%-30% in the cells from theophylline-treated rats at all insulin concentrations tested. The half-maximally effective concentration of insulin was not altered (6.5 +/- 0.5 and 6.7 +/- 0.5 mU/l in control and treated cells respectively), suggesting a post-insulin binding defect. This was confirmed by the finding that 125I-insulin binding to the cells was not altered. Adenosine receptor number and affinity (measured on detergent-solubilized adipocyte extracts using 125I-hydroxyphenylisopropyl adenosine) was also not changed by theophylline treatment. We conclude that theophylline administration causes decreased glucose transport rates in rat adipocytes at a post-insulin binding level. Thus, chronic adenosine receptor blockade impairs adipocyte glucose transport, suggesting that adenosine is involved in long-term regulation of glucose metabolism in adipose tissue.
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