Controlled Glucose Oscillations May Restore Insulin Production

The DOM predicted that an oscillatory stimulus using pulses of glucose to the bloodstream has the potential to reactivate the insulin clock within β-cells that had been halted by exposure to excess glucose.

The researchers tested the hypothesis in a non-diabetic islets of Langerhans mice model. Using a specially engineered microfluidic device, they first delivered a high, steady, glucose stream; as expected, the insulin clock within the mouse islets was deactivated. But when controlled pulses of glucose were reapplied to the islets, the insulin clock was restarted. Moreover, when the flow of glucose followed a feedback loop simulating liver activity, the reactivated islets also recruited other islets to restart their insulin clock. The study was published on October 26, 2016, in PLOS Computational Biology.

“Microfluidics and mathematical modeling can be used together to gain new insights into the mechanisms for hormone secretion,” concluded senior author Richard Bertram, PhD, of the FSU department of mathematics and programs in neuroscience and molecular biophysics. “Our results have potential implications for enhancing insulin pulsatility, and therefore mitigating the development of type 2 diabetes.”

Pancreatic islets manage elevations in blood glucose level by secreting insulin into the bloodstream, governed by islet oscillations such as bursting electrical activity and periodic Ca2+ entry in β-cells. In healthy individuals, β-cells release regular pulses of insulin to restrict the amount of glucose released by the liver, as well as impel body tissues to absorb the glucose. However, in hyperglycemia, a hallmark of type 2 diabetes, the excess glucose suppresses the "inner clock" of β-cells that controls the rhythm of insulin pulses, reducing insulin production.

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