Gut-pancreas axis in the control of insulin secretion in streptozotocin-resistant rats

IF 2.2 3区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Biochemical and biophysical research communications Pub Date : 2025-03-08 Epub Date: 2025-02-13 DOI:10.1016/j.bbrc.2025.151487

Kazuhiro Nomura , Yuki Yamasaki , Kana Takeji , Sachie Deha , Kaho Yamashita , Yuna Izumi-Mishima , Sonoko Yasui-Yamada , Masashi Kuroda , Nagakatsu Harada , Tadahiro Kitamura , Yasuo M. Tsutsumi , Rie Tsutsumi , Yutaka Nakaya , Hiroshi Sakaue

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Abstract

The Spontaneously Running Tokushima Shikoku (SPORTS) rat is characterized by hyperactive behavior but is also a potential model for studies of the role of the gut-pancreas axis in the regulation of insulin secretion. We here explored the role of ghrelin, a hormone associated with appetite regulation, in insulin dynamics within the context of streptozotocin (STZ) resistance in SPORTS rats. Comprehensive analyses—including histological examinations, gene expression profiling, and assessment of metabolic parameters—revealed that SPORTS rats are resistant to STZ-induced pancreatic injury and that, in addition to low circulating ghrelin levels, they manifest increased circulating levels of active glucagon-like peptide–1 (GLP-1) and upregulated expression of Pdx1 in the pancreas. Ghrelin administration attenuated the STZ resistance of these rats, with suppression of GLP-1 and downregulation of Pdx1 expression being implicated in this effect. Our results highlight the complex interplay among ghrelin, GLP-1, and insulin dynamics, and they suggest potential new therapeutic targets for diabetes.

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肠胰轴对链脲佐菌素耐药大鼠胰岛素分泌的控制

自发奔跑的德岛四国（SPORTS）大鼠的特征是过度活跃的行为，但也是研究肠-胰轴在胰岛素分泌调节中的作用的潜在模型。我们在这里探讨了胃饥饿素（一种与食欲调节相关的激素）在运动大鼠链脲佐菌素（STZ）抗性背景下胰岛素动力学中的作用。包括组织学检查、基因表达谱和代谢参数评估在内的综合分析显示，sport大鼠对stz诱导的胰腺损伤具有抗性，除了循环胃饥饿素水平低外，它们还表现出循环中活性胰高血糖素样肽-1 （GLP-1）水平升高和胰腺中Pdx1表达上调。通过抑制GLP-1和下调Pdx1的表达，Ghrelin降低了这些大鼠对STZ的抗性。我们的研究结果强调了胃饥饿素、GLP-1和胰岛素动力学之间复杂的相互作用，并为糖尿病提供了潜在的新治疗靶点。

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来源期刊

Biochemical and biophysical research communications 生物-生化与分子生物学

CiteScore

6.10

自引率

0.00%

发文量

1400

审稿时长

14 days

期刊介绍： Biochemical and Biophysical Research Communications is the premier international journal devoted to the very rapid dissemination of timely and significant experimental results in diverse fields of biological research. The development of the "Breakthroughs and Views" section brings the minireview format to the journal, and issues often contain collections of special interest manuscripts. BBRC is published weekly (52 issues/year).Research Areas now include: Biochemistry; biophysics; cell biology; developmental biology; immunology ; molecular biology; neurobiology; plant biology and proteomics