Department of Biomedical Engineering, The George Washington University, Washington, District of Columbia, USA.
LabTAU, INSERM, Centre Léon Bérard, Université Lyon 1, Université Lyon 1, Université Lyon, Lyon, France.
J Ultrasound Med. 2021 Dec;40(12):2709-2719. doi: 10.1002/jum.15661. Epub 2021 Feb 17.
Our previously published studies showed the potential of therapeutic ultrasound (US) as a novel non-pharmacological alternative for the treatment of secretory deficiencies in type 2 diabetes. Despite showing enhanced insulin release from beta cells, these studies did not explore the potential effects of US treatment on other cells in the islets of Langerhans such as glucagon-secreting alpha cells or acinar cells of the exocrine pancreas.
We applied US parameters found capable of safely stimulating insulin secretion from pancreatic beta cells (f = 800 kHz, I = 0.5-1 W/cm , 5 minutes) to a diced rabbit pancreas model in culture plates (n = 6 per group). Released quantities of insulin and glucagon in response to US treatment were measured by collecting aliquots of the extracellular medium prior to the start of the treatment (t = 0 minute), immediately after treatment (t = 5 minutes) and 30 minutes after the end of treatment (t = 35 minutes). Potential release of digestive enzyme alpha-amylase as a result of US treatment was evaluated in rabbit pancreas experiments. Preliminary studies were also performed in a small number of human pancreatic islets in culture plates (n = 3 per group). The general integrity of the US-treated rabbit pancreatic tissue and human pancreatic islets was evaluated through histological analysis.
While sham-treated rabbit pancreas samples showed decreased extracellular insulin content, there was an increase in insulin release at t = 5 minutes from samples treated with US at 800 kHz and 1 W/cm (P <.005). Furthermore, no further insulin release was detected at t = 35 minutes. No statistically significant difference in extracellular glucagon and alpha-amylase concentrations was observed between US-treated and sham rabbit pancreas groups. Preliminary studies in human islets appeared to follow trends observed in rabbit pancreas studies. Islet and other pancreatic tissue integrity did not appear to be affected by the US treatment.
A potential US-based strategy for enhanced insulin release would require optimization of insulin secretion from pancreatic beta cells while minimizing glucagon and pancreatic enzyme secretions.
我们之前的研究表明，治疗性超声（US）作为一种新型非药物替代疗法，具有治疗 2 型糖尿病分泌不足的潜力。尽管这些研究显示超声治疗增强了β细胞的胰岛素释放，但它们并未探讨 US 治疗对胰岛中其他细胞（如胰高血糖素分泌的α细胞或外分泌胰腺的腺泡细胞）的潜在影响。
我们将能够安全刺激胰腺β细胞胰岛素分泌的 US 参数（f=800kHz，I=0.5-1W/cm2，5 分钟）应用于培养板中的兔胰腺切块模型（每组 n=6）。在治疗开始前（t=0 分钟）、治疗后立即（t=5 分钟）和治疗结束后 30 分钟（t=35 分钟）收集细胞外液的等分试样，以测量对 US 治疗的胰岛素和胰高血糖素释放量。通过兔胰腺实验评估 US 治疗导致的消化酶α-淀粉酶的潜在释放。在培养板中的少量人胰岛中也进行了初步研究（每组 n=3）。通过组织学分析评估 US 处理的兔胰腺组织和人胰岛的整体完整性。
虽然假处理的兔胰腺样本显示细胞外胰岛素含量降低，但在用 800kHz 和 1W/cm2 的 US 处理的样本中，t=5 分钟时胰岛素释放增加（P<.005）。此外，在 t=35 分钟时未检测到进一步的胰岛素释放。在 US 处理和假兔胰腺组之间，细胞外胰高血糖素和α-淀粉酶浓度没有统计学上的显著差异。在人胰岛中的初步研究似乎遵循了在兔胰腺研究中观察到的趋势。胰岛和其他胰腺组织的完整性似乎没有受到 US 治疗的影响。
一种基于 US 的增强胰岛素释放的潜在策略需要优化从胰腺β细胞中分泌胰岛素，同时最小化胰高血糖素和胰腺酶的分泌。
