Alanine and hyperosmolarity are responsible for the stimulation of cardiomyocyte glucose transport by samples containing a glucose tolerance factor

Abstract

Low-molecular-weight, cationic samples, that were previously reported to contain a glucose tolerance factor, were obtained by partial purification from yeast extract. These samples increased the rate of glucose transport in isolated cardiomyocytes 2.0- to 2.5-fold. A further purification by gel filtration led to the separation of two active components that were identified as (i) L-alanine and (ii) an elevated osmolarity. Moreover, the effect of partially purified fractions (before gel filtration) (ii) was mimicked by the depletion with alanine dehydrogenase and (ii) was mimicked by the additive action of alanine and of a hyperosmolar medium. These findings indicate that the effect of this partially purified material is not accounted for by a putative glucose tolerance factor. Interestingly, alanine elicited its effect at concentrations that correspond to physiological plasma values, which suggests that this amino acid might be involved in the regulation of glucose transport in cardiomyocytes. Furthermore, the effect of alanine was prevented by DL-cycloserine (1 mM) or aminooxyacetate (1 mM), but not by cycloheximide (35 μM), indicating that (a) transamination reaction(s), but not protein synthesis, is required.