The VGF-derived peptide TLQP-62 modulates insulin secretion and glucose homeostasis
The VGF-derived peptide TLQP-62 modulates insulin secretion and glucose homeostasis
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DOI：
10.1530/jme-14-0313
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发表时间：
2015-06-01
影响因子：
3.5
通讯作者：
Possenti, Roberta
中科院分区：
文献类型：
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作者：
Petrocchi-Passeri, Pamela;Cero, Cheryl;Possenti, Roberta
胰岛素分泌控制对葡萄糖稳态至关重要。由胰岛细胞以及壁内和自主神经元分泌的旁分泌和自分泌分子控制调节胰岛素分泌的不同激素的释放。在胰岛中，大量存在的颗粒蛋白VGF（nonacronymic;无关的VEGF）表明，它的一些蛋白水解衍生肽可以调节激素的释放。因此，在本研究中，我们筛选了几种VEGF衍生肽诱导胰岛素分泌的能力，我们确定了VGF C-末端肽TLQP-62作为最有效的片段。TLQP-62在几种胰岛素瘤细胞系中诱导基础胰岛素分泌以及葡萄糖刺激的胰岛素分泌的有效增加。我们发现这种肽通过增加细胞内钙动员和胰岛素1基因的快速表达来刺激胰岛素释放。此外，外周注射TLQP-62可改善小鼠的葡萄糖耐量。总之，目前的研究结果表明，TLQP-62，作为一种内分泌，旁分泌，或自分泌因子，可以被认为是一种新的，强大的促胰岛素肽，可以针对创新的抗糖尿病药物发现计划。
Insulin secretion control is critical for glucose homeostasis. Paracrine and autocrine molecules secreted by cells of the islet of Langerhans, as well as by intramural and autonomic neurons, control the release of different hormones that modulate insulin secretion. In pancreatic islets, the abundant presence of the granin protein VGF (nonacronymic; unrelated to VEGF) suggests that some of its proteolytically derived peptides could modulate hormone release. Thus, in the present study, we screened several VGF-derived peptides for their ability to induce insulin secretion, and we identified the VGF C-terminal peptide TLQP-62 as the most effective fragment. TLQP-62 induced a potent increase in basal insulin secretion as well as in glucose-stimulated insulin secretion in several insulinoma cell lines. We found that this peptide stimulated insulin release via increased intracellular calcium mobilization and fast expression of the insulin 1 gene. Moreover, the peripheral injection of TLQP-62 in mice improved glucose tolerance. Together, the present findings suggest that TLQP-62, acting as an endocrine, paracrine, or autocrine factor, can be considered a new, strong insulinotropic peptide that can be targeted for innovative antidiabetic drug discovery programs.