The effects on islet hormone secretion of the synthetic replicates of two peptides with potent GH-releasing activity isolated from human pancreatic islet cell tumors (GRF-40 and GRF-44) were studied using the isolated, perfused dog pancreas. GRF-40 produced a dose-dependent stimulation of insulin, glucagon, and somatostatin secretion. The responses to GRF-40 were modified by the prevailing glucose level: higher insulin and somatostatin and lower glucagon responses were obtained at high rather than low glucose. In contrast, GRF-44 did not produce any stimulation of the endocrine pancreas. In vivo GRF-40 and GRF-44 elicited identical pronounced growth hormone responses in the rat. The findings reported here provide support that pancreatic insulin and glucagon are modulated by GRF-40 with somatostatin as its inhibitory counterpart. The question, whether GRF-40 is of physiologic relevance in the regulation of the endocrine pancreas, must await evidence that it is present and releasable from the pancreas.

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