Somatostatin, the hypothalamic growth hormone release inhibitory factor (GHRIF), directly inhibits both the first and second phases of insulin secretion. The sensitivities of these two phases of insulin secretion to somatostatin differ remarkably. The first phase of secretion is approximately 25 to 50 times more sensitive to somatostatin inhibition than is the second phase. In addition, somatostatin inhibition of insulin secretion during the second phase is "reversed" by supplemental calcium, whereas the somatostatin effect on the first phase is unaffected by additional calcium. These findings suggest that the cellular events which produce the two phases of insulin secretion are separate processes, and that somatostatin has a dual mechanism of action in inhibiting insulin secretion.
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