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.