Ultrasound Stimulation of Pancreatic Beta Cells

描述（由申请人提供）：2型糖尿病是一种复杂的代谢性疾病，在美国和世界范围内已达到流行程度。美国的糖尿病患病率约为8.3%；全球约有1.5亿病例，预计这一数字在未来20年将翻一番。糖尿病增加了发生慢性并发症的风险，包括动脉粥样硬化性血管疾病（冠状动脉疾病、中风和周围血管疾病）、视网膜病变、肾病和神经病变。这些并发症导致过早死亡、视力受损和失明、终末期肾病和截肢，并产生巨大的卫生保健费用。2型糖尿病是多种代谢异常的相互作用的结果，包括外周组织胰岛素敏感性降低和胰腺b细胞胰岛素分泌不足。临床试验表明，强化血糖控制和减少其他心血管危险因素可以减少慢性并发症的发生。然而，控制2型糖尿病通常是困难的。许多患者对改变生活方式的建议依从性较差，药理学管理通常需要多种药物的复杂治疗，并且随着时间的推移会失去其有效性。因此，人们对寻找治疗糖尿病的替代方法越来越感兴趣。本提案的目的是探索一种新的，非药物的方法，利用超声能量的应用来增加胰腺b细胞的胰岛素释放。此前，低强度治疗性超声已被用于产生细胞膜通透性的可逆性改变、神经组织的调节、脂肪细胞中脂联素激素的释放以及肾上腺细胞中肾上腺素和去甲肾上腺素的释放。我们的实验将集中在确定超声应用在刺激胰岛素从胰腺b细胞释放的有效性和安全性。如果试验成功，我们的方法可能最终导致治疗糖尿病和其他分泌性疾病的新方法。

DESCRIPTION (provided by applicant): Type 2 diabetes mellitus is a complex metabolic disease that has reached epidemic proportions in the United States and around the world. The prevalence of diabetes in the United States is approximately 8.3%; worldwide, there are about 150 million cases, a number expected to double in the next 20 years. Diabetes increases the risk of development of chronic complications including atherosclerotic vascular diseases (coronary artery disease, stroke and peripheral vascular disease), retinopathy, nephropathy and neuropathies. These complications result in premature death, vision impairment and blindness, end stage kidney disease and amputation as well as engendering enormous health care costs. Type 2 diabetes results from the interplay of multiple metabolic abnormalities including decreased insulin sensitivity of peripheral tissues and insufficient insulin secretion from pancreatic b-cells. Clinical trials have shown that intensive blood glucose control together with reduction of the other cardiovascular risk factors can reduce the development of chronic complications. However, controlling type 2 diabetes is often difficult. Many patients are poorly compliant with lifestyle change recommendations, and pharmacological management routinely requires complex therapy with multiple medications, and loses its effectiveness over time. Thus, there is a growing interest in finding alternative methods for the treatment of diabetes. The objective of this proposal is to explore a novel, non- pharmacological approach that utilizes the application of ultrasound energy to augment insulin release from pancreatic b-cells. Low-intensity therapeutic ultrasound has been utilized before in production of reversible changes in cell membrane permeability, modulation of neural tissues, and enhancement of release of the adiponectin hormone from adipose cells, and epinephrine and norepinephrine from adrenal cells. Our experiments will focus on determination of effectiveness and safety of ultrasound application in stimulation of insulin release from the pancreatic b-cells. If shown successful our approach may eventually lead to new methods in the treatment of diabetes and other secretory diseases.