title: Ultrasound Stimulation of Insulin Release from Pancreatic Beta Cells as a Potential Novel Treatment for Type 2 Diabetes.
abstract: Type 2 diabetes mellitus is a complex metabolic disease that has reached epidemic proportions in the United States and around the world. This disease is characterized by loss of insulin secretion and, eventually, destruction of insulin-producing pancreatic beta cells. Controlling type 2 diabetes is often difficult as pharmacological management routinely requires complex therapy with multiple medications, and loses its effectiveness over time. The objective of this study was to explore the effectiveness of a novel, non-pharmacological approach that uses the application of ultrasound energy to augment insulin release from rat INS 832/13 beta cells. The cells were exposed to unfocused ultrasound for 5 min at a peak intensity of 1 W/cm2and frequencies of 400 kHz, 600 kHz, 800 kHz and 1 MHz. Insulin release was measured with enzyme-linked immunosorbent assay and cell viability was assessed via the trypan blue dye exclusion test. A marked release (approximately 150 ng/106cells, p < 0.05) of insulin was observed when beta cells were exposed to ultrasound at 400 and 600 kHz as compared with their initial control values; however, this release was accompanied by a substantial loss in cell viability. Ultrasound application at frequencies of 800 kHz resulted in 24 ng/106cells released insulin (p < 0.05) as compared with its unstimulated base level, while retaining cell viability. Insulin release from beta cells caused by application of 800-kHz ultrasound was comparable to that reported by the secretagogue glucose, thus operating within physiological secretory capacity of these cells. Ultrasound has potential as a novel and alternative method to current approaches aimed at correcting secretory deficiencies in patients with type 2 diabetes.
authors.affiliation: Department of Biomedical Engineering, The George Washington University, Washington, DC, USA. Electronic address: isuarez@gwu.edu.
authors.forename: Ivan
authors.initials: I
authors.lastname: Suarez Castellanos
authors.affiliation: Department of Biological Sciences, The George Washington University, Washington, DC, USA.
authors.forename: Aleksandar
authors.initials: A
authors.lastname: Jeremic
authors.affiliation: Department of Endocrinology, Medical Faculty Associates, The George Washington University, Washington, DC, USA.
authors.forename: Joshua
authors.initials: J
authors.lastname: Cohen
authors.affiliation: Department of Biomedical Engineering, The George Washington University, Washington, DC, USA.
authors.forename: Vesna
authors.initials: V
authors.lastname: Zderic
mesh_terms: D000818:Animals; D002460:Cell Line; D003692:Delayed-Action Preparations / Q000008:administration & dosage; D003924:Diabetes Mellitus, Type 2 / Q000000981:diagnostic imaging / Q000628:therapy*; D019220:High-Energy Shock Waves; D007004:Hypoglycemic Agents / Q000008:administration & dosage; D007328:Insulin / Q000096:biosynthesis*; D050417:Insulin-Secreting Cells / Q000378:metabolism* / Q000528:radiation effects*; D051381:Rats; D013010:Sonication / Q000379:methods*; D016896:Treatment Outcome; D014464:Ultrasonic Therapy / Q000379:methods*
chemical_list: D003692:Delayed-Action Preparations; D007004:Hypoglycemic Agents; D007328:Insulin
keywords: Cell stimulation; Insulin; Pancreatic beta cells; Type 2 diabetes; Ultrasound therapy