Analyzing Gene Expression After Administration of Low-Intensity Therapeutic Ultrasound in Human Islet Cells.

Analyzing Gene Expression After Administration of Low-Intensity Therapeutic Ultrasound in Human Islet Cells.
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分析人胰岛细胞中低强度治疗性超声后的基因表达。

DOI:
10.1002/jum.16441
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发表时间:
2024
期刊:
Journal of ultrasound in medicine : official journal of the American Institute of Ultrasound in Medicine
影响因子:
--
通讯作者:
Zderic,Vesna
Zderic,Vesna
中科院分区:
--
文献类型:
--
作者:
Hill,John;Messina,James;Jeremic,Aleksandar;Zderic,Vesna

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目的糖尿病是一种复杂的异质性代谢性疾病,严重影响世界人口。尽管存在许多治疗方法,包括二甲双胍、磺脲类药物和胰升糖素样肽-1(GLP)受体激动剂等药物,但人们对寻找非侵入性治疗该疾病的替代方法越来越感兴趣。此前已有研究表明,低强度超声刺激小鼠胰腺β细胞可以诱导胰岛素分泌,作为治疗这种疾病的一种潜在方法。这是因为治疗性超声具有诱导生物效应的能力,同时选择性地聚焦于组织深处,允许调节胰腺激素的分泌,以缓解胰岛素水平的不足。方法将800  功率/cm2的超声作用于供体胰岛,连续5 分钟,即100%占空比,然后进行1 小时的孵育和RT-qPCR,以评估超声刺激对基因表达的影响。这些基因是胰岛素(INS)、胰高血糖素(Glu)、胰淀素(AMY)和结合免疫球蛋白(Bip)。9个供体人胰岛用于评估胰岛素和胰升糖素的分泌,而8个样本用于胰淀素和Bip的分泌。计算折叠变化(Fc),分析超声刺激对供体胰岛细胞基因表达的影响。以高糖和thapsigargin处理的胰岛作为阳性对照。结果超声刺激对所有被测基因(INS FC = 1.15,P值 = .5692;Glu FC = 1.60,P值 = .2231;AMY FC,P值 = .2863;BIP FC = 2.68,P值 = .3907)的表达没有显著影响。
ObjectivesDiabetes mellitus is a complex heterogenous metabolic disease that significantly affects the world population. Although many treatments exist, including medications such as metformin, sulfonylureas, and glucagon‐like peptide‐1 (GLP) receptor agonist, there is growing interest in finding alternative methods to noninvasively treat this disease. It has been previously shown that low‐intensity ultrasound stimulation of pancreatic β‐cells in mice can elicit insulin secretion as a potential treatment for this disease. This is desirable as therapeutic ultrasound has the ability to induce bioeffects while selectively focusing deep within tissues, allowing for modulation of hormone secretion in the pancreas to mitigate insufficient levels of insulin.MethodsExactly 800 kHz ultrasound with intensity 0.5 W/cm2was administered 5 minutes continuously, that is, 100% duty cycle, to donor pancreatic human islets, followed by 1 hour incubation and RT‐qPCR to assess the effect of ultrasound stimulation on gene expression. The genes were insulin (INS), glucagon (Glu), amylin (Amy), and binding immunoglobulin protein (BiP). Nine donor pancreatic human islets were used to assess insulin and glucagon secretion, while eight samples were used for amylin and BiP. Fold change (FC) was calculated to analyze the effect of ultrasound stimulation on the gene expression of the donor islet cells. High‐glucose and thapsigargin‐treated islets were utilized as positive controls. Cell viability testing was done using a Trypan Blue Exclusion Test.ResultsUltrasound stimulation did not cause a statistically significant upregulation in any of the tested genes (INS FC = 1.15,P‐value = .5692; Glu FC = 1.60,P‐value = .2231; Amy FC,P‐value = .2863; BiP FC = 2.68,P‐value = .3907).ConclusionsThe results of this study show that the proposed ultrasound treatment parameters do not appear to significantly affect gene expression of any gene tested.
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