Abstract
BackgroundOur previous studies have indicated that ultrasound can stimulate the release of insulin from pancreatic beta cells, providing a potential novel treatment for type 2 diabetes. The purpose of this study was to explore the temporal dynamics and Ca2+-dependency of ultrasound-stimulated secretory events from dopamine-loaded pancreatic beta cells in an in vitro setup.MethodsCarbon fiber amperometry was used to detect secretion from INS-1832/13 beta cells in real time. The levels of released insulin were also measured in response to ultrasound treatment using insulin-specific ELISA kit. Beta cells were exposed to continuous wave 800 kHz ultrasound at intensities of 0.1 W/cm2, 0.5 W/cm2 and 1 W/cm2 for several seconds. Cell viability tests were done with trypan blue dye exclusion test and MTT analysis.ResultsCarbon fiber amperometry experiments showed that application of 800 kHz ultrasound at intensities of 0.5 and 1 W/cm2 was capable of stimulating secretory events for durations lasting as long as the duration of the stimulus. Furthermore, the amplitude of the detected peaks was reduced by 64% (p < 0.01) when extracellular Ca2+ was chelated with 10 mM EGTA in cells exposed to ultrasound intensity of 0.5 W/cm2. Measurements of released insulin in response to ultrasound stimulation showed complete inhibition of insulin secretion by chelating extracellular Ca2+ with 10 mM EGTA (p < 0.01). Viability studies showed that 800 kHz, 0.5 W/cm2 ultrasound did not cause any significant effects on viability and metabolic activity in cells exposed to ultrasound as compared to sham-treated cells.ConclusionsOur results demonstrated that application of ultrasound was capable of stimulating the release of insulin from pancreatic beta cells in a safe, controlled and Ca2+-dependent manner.
Highlights
Our previous studies have indicated that ultrasound can stimulate the release of insulin from pancreatic beta cells, providing a potential novel treatment for type 2 diabetes
The accepted model of stimulus-induced secretion in pancreatic beta cells involves a sequence of events including the closure of ATP-sensitive potassium channels, membrane depolarization, an influx of Ca2+ leading to a rise in the intracellular calcium concentration, and exocytosis of insulin [9, 10]
The impairment of insulin action – the interaction between insulin and peripheral tissues – is found in almost all type 2 diabetes patients, it is the impairment of insulin secretion that accounts for the development of hyperglycemia and the progression of the disease [16]
Summary
Our previous studies have indicated that ultrasound can stimulate the release of insulin from pancreatic beta cells, providing a potential novel treatment for type 2 diabetes. According to the United Kingdom Prospective Diabetes Study (UKPDS), beta cell function is already reduced by up to 50% at the time that diabetes is diagnosed, and continues to decline progressively, regardless of treatment, in subsequent years [17]. This finding demonstrates that substantial defects in beta cell function develop much earlier than the diagnosis of hyperglycemia and that the progression of the disease is mainly driven by the decline of insulin secretion. Current pharmacological treatment courses of type 2 diabetes are very complex and include many side effects which can result in further complications [19,20,21,22,23]
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