Islet neogenesis-associated protein (INGAP): The role of its endogenous production as a positive modulator of insulin secretion

Luis E. Flores , Héctor Del Zotto , Florencia Fragapane , Bárbara Maiztegui , Carolina L. Román , Antonio C. Boschero , Juan J. Gagliardino
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引用次数: 5

Abstract

Islet neogenesis-associated protein (INGAP) is a peptide found in pancreatic exocrine-, duct- and islet- non-β-cells from normal hamsters. Its increase induced by either its exogenous administration or by the overexpression of its gene enhances β-cell secretory function and increases β-cell mass by a combination of stimulation of cell replication and islet neogenesis and reduction of β-cell apoptosis. We studied the potential modulatory role of endogenous INGAP in insulin secretion using two different experimental approaches. Hamster islets transfected with INGAP-small interfering RNA (INGAP-siRNA) were used to study glucose-stimulated insulin secretion (GSIS). In parallel, freshly isolated islets were incubated with high glucose and the same concentration of either a specific anti-INGAP rabbit serum or normal rabbit serum. INGAP-siRNA transfected islets reduced their INGAP mRNA and protein content by 35.1% and 47.2%, respectively whereas GSIS decreased by 25.8%. GSIS by transfected islets attained levels comparable to those recorded in control islets when INGAP pentadecapeptide (INGAP-PP) was added to the culture medium. INGAP antibody in the medium decreased significantly GSIS in a dose-dependent manner. These results indicate that endogenous INGAP plays a “physiological” positive modulatory role in insulin secretion, supporting its possible use in the treatment of prediabetes and Type 2 diabetes.

胰岛新生相关蛋白(INGAP):其内源性生产作为胰岛素分泌的积极调节剂的作用
胰岛新生相关蛋白(INGAP)是一种存在于正常仓鼠胰腺外分泌、胰岛导管和胰岛非β细胞中的肽。通过外源性给药或其基因的过度表达诱导其增加,通过刺激细胞复制和胰岛新生以及减少β细胞凋亡,增强β细胞分泌功能并增加β细胞质量。我们使用两种不同的实验方法研究了内源性INGAP在胰岛素分泌中的潜在调节作用。用转染ingap -小干扰RNA (INGAP-siRNA)的仓鼠胰岛研究葡萄糖刺激胰岛素分泌(GSIS)。同时,新鲜分离的胰岛用高葡萄糖和相同浓度的抗ingap兔血清或正常兔血清孵育。转染INGAP- sirna的胰岛INGAP mRNA和蛋白含量分别降低了35.1%和47.2%,而GSIS则降低了25.8%。当向培养基中添加INGAP五肽(INGAP- pp)时,转染胰岛的GSIS达到与对照胰岛相当的水平。培养基中的INGAP抗体呈剂量依赖性显著降低GSIS。这些结果表明,内源性INGAP对胰岛素分泌具有“生理性”正向调节作用,支持其在治疗前驱糖尿病和2型糖尿病中的可能应用。
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来源期刊
Regulatory Peptides
Regulatory Peptides 医学-内分泌学与代谢
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审稿时长
2 months
期刊介绍: Regulatory Peptides provides a medium for the rapid publication of interdisciplinary studies on the physiology and pathology of peptides of the gut, endocrine and nervous systems which regulate cell or tissue function. Articles emphasizing these objectives may be based on either fundamental or clinical observations obtained through the disciplines of morphology, cytochemistry, biochemistry, physiology, pathology, pharmacology or psychology.
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