Prevention of clonidine-stimulated hyperglycemia by thyrotropin-releasing hormone.

Central injection of thyrotropin-releasing hormone (TRH) prevented the rise in plasma glucose due to clonidine challenge in mice. This antihyperglycemic action was dose-related, dependent upon the structural integrity of the peptide, dissociated from the peptide's hypophysiotropic influences, and coupled to reversal of clonidine's suppressive action of insulin release. TRH was effective in preventing the rise in plasma glucose when given at different times before clonidine (up to two hours), and it also reversed the hyperglycemia when administered 30 min after clonidine, when plasma glucose was already exceedingly high. The results suggest that TRH is able to physiologically oppose clonidine-induced hyperglycemia by acting in a specific and durable manner upon central mechanisms which modulate insulin secretion.