Drucker D J, Philippe J, Mojsov S, Chick W L, Habener J F
Proc Natl Acad Sci U S A. 1987 May;84(10):3434-8. doi: 10.1073/pnas.84.10.3434.
Insulin secretion is controlled by a complex set of factors. Although blood glucose levels serve as the major stimulus of insulin secretion in mammals, insulin release is also modulated by amino acids, catecholamines, glucagon, and other, intestinal hormones. The identification of factors that modulate insulin production has engendered much interest because of their potential importance in the altered dynamics of insulin secretion in response to glucose characteristic of maturity-onset diabetes mellitus. Decoding of the glucagon gene has uncovered two additional glucagon-like peptides encoded in proglucagon, the polypeptide precursor of glucagon. One of these peptides, glucagon-like peptide I, is processed from proglucagon in two forms, of 31 and 37 amino acids. We report that the smaller of the two glucagon-like peptides potently increases cAMP levels, insulin mRNA transcripts, and insulin release in cultured rat insulinoma cells. These results indicate that glucagon-like peptide I may be a physiologic modulator of insulin gene expression.
胰岛素分泌受一系列复杂因素的控制。尽管血糖水平是哺乳动物胰岛素分泌的主要刺激因素，但胰岛素释放也受到氨基酸、儿茶酚胺、胰高血糖素和其他肠道激素的调节。由于调节胰岛素产生的因素在成年型糖尿病特征性的葡萄糖反应性胰岛素分泌动态变化中具有潜在重要性，因此对这些因素的识别引起了广泛关注。胰高血糖素基因的解码揭示了胰高血糖素（一种多肽前体）中编码的另外两种胰高血糖素样肽。其中一种肽，即胰高血糖素样肽I，以前胰高血糖素的两种形式（31和37个氨基酸）进行加工。我们报告，两种胰高血糖素样肽中较小的一种能显著提高培养的大鼠胰岛素瘤细胞中的cAMP水平、胰岛素mRNA转录本以及胰岛素释放。这些结果表明，胰高血糖素样肽I可能是胰岛素基因表达的生理调节因子。
