Increasing concentrations of D-glucose (1 to 25 mM) inhibited somatostatin, thyrotrophin-releasing hormone (TRH) and growth hormone-releasing hormone (GHRH) release from incubated adult rat hypothalami in a stereospecific manner. In contrast, the effects of D-and L-glucose on luteinizing hormone-releasing hormone release were virtually identical. Increasing concentrations of D-glucose also inhibited somatostatin release following depolarization with high K', but had no obvious effect on depolarizationinduced TRH or GHRH release when compared with L-glucose.In conclusion, D-glucose exerts a potent, dose-related modulatory action on the release of rat hypothalamic TRH and GHRH as well as somatostatin in vifro. Further studies are required to establish any physiological relevance of glucose in the modulation of these hypothalamic neuropeptides.Hoth thyrotrophin-releasing hormone (TRH) and somatostatin rnay affect circulating glucose concentrations through either peripheral actions on gastrointestinal hormone release or central effects on hypothalamic autonomic centres, or both (1-5). The effects of growth hormone-releasing hormone (GHRH) on glucose status are less clear but it is has been reported that administration to humans does not affect circulating glucose levels (6). 7 he inhibitory effects of glucose on hypothalamic somatostatin release in vitro have been reported several times (7-9) while luteinizing hormone-releasing hormone (LHRH) release is relatively unaffected (8). Hitherto there are no reports of the actions of glucose on the release of hypothalamic TRH and GHRH in )./lro.The aim of this study was to investigate whether glucose influences TRH and GHRH release from rat hypothalamus in wwo using an experimental model previously fully validated for the study of neuropeptide and neurotransmitter interactions (10, 1 1 ) and used by other groups for the study of the actions of glucose (7-9). In order to investigate the stereospecificity of any observed effects and to control for changes in osmolality, we have compared the effects of different concentrations of the active (D) and the inactive (L) isomers of glucose on the release of TRH, GHRH, somatostatin and LHRH.
ResultsIncreasing concentrations of D-glucose (1 to 25 mM) inhibited somatostatin secretion (1 mM; 166.0f 16.0 vs 25 mM; 61.5f9.4 pg somatostatin/hypothalamus/20 min respectively, P < 0.001). Release in the absence of glucose was 240.0 f 26.5 pg somatostatin/hypothalamus/20 min (NS vs 1 mM L-glucose). (Fig. 1~) TRH release also decreased with increasing concentration of D-glucose (1 mM; 9.6f0.8 vs 25 mM 4.6f0.5 pg TRH/hypothalamus/20 min, P