Betacellulin improves glucose metabolism by promoting conversion of intraislet precursor cells to β-cells in streptozotocin-treated mice

Betacellulin improves glucose metabolism by promoting conversion of intraislet precursor cells to β-cells in streptozotocin-treated mice
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DOI:
10.1152/ajpendo.00120.2003
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发表时间:
2003-09-01
影响因子:
5.1
通讯作者:
Kojima, I
Kojima, I
中科院分区:
医学2区
文献类型:
--
作者:
Li, L;Seno, M;Kojima, I

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β -纤维素蛋白(BTC)诱导实验性糖尿病患者胰腺β细胞分化并促进β细胞再生。本研究旨在确定BTC是否能改善小鼠高剂量链脲佐菌素(STZ)诱导的严重糖尿病的糖代谢。雄性ICR小鼠注射200杯/克STZ,同时每天给药不同剂量的BTC,连续14天。stz注射小鼠血浆葡萄糖浓度升高至bb0 ~ 500mg /dl。0.2杯/g的BTC显著降低血糖浓度,但浓度再高则无效。BTC的效果在第4天明显,但在第6天或之后变得较小。0.1、0.2杯/g BTC组小鼠血浆胰岛素浓度和胰岛素含量显著升高。BTC治疗显著增加了每个胰岛的β细胞数量以及胰岛素阳性胰岛的数量。胰岛内5-溴-2-脱氧尿嘧啶/生长抑素阳性细胞和胰十二指肠同源盒-1/生长抑素阳性细胞数量显著增加。这些结果表明,BTC通过促进β细胞(主要来自生长抑素阳性的胰岛细胞)的新生来改善高剂量STZ诱导的高血糖。
Beta-cellulin (BTC) induces differentiation of pancreatic beta-cells and promotes regeneration of beta-cells in experimental diabetes. The present study was conducted to determine if BTC improved glucose metabolism in severe diabetes induced by a high dose of streptozotocin (STZ) in mice. Male ICR mice were injected with 200 mug/g ip STZ, and various doses of BTC were administered daily for 14 days. The plasma glucose concentration increased to a level of >500 mg/dl in STZ-injected mice. BTC (0.2 mug/g) significantly reduced the plasma glucose concentration, but a higher concentration was ineffective. The effect of BTC was marked by day 4 but became smaller on day 6 or later. The plasma insulin concentration and the insulin content were significantly higher in mice treated with 0.1 and 0.2 mug/g BTC. BTC treatment significantly increased the number of beta-cells in each islet as well as the number of insulin-positive islets. Within islets, the numbers of 5-bromo-2-deoxyuridine/somatostatin-positive cells and pancreatic duodenal homeobox-1/somatostatin-positive cells were significantly increased by BTC. These results indicate that BTC improved hyperglycemia induced by a high dose of STZ by promoting neoformation of beta-cells, mainly from somatostatin-positive islet cells.