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The electrophysiology of insulin-secreting cells

According to the International Diabetes Federation, the prevalence of diabetes is expected to reach 9.8 % of the adult European population by 2025. To elucidate the dynamics of insulin secretion in patients with diabetes, European scientists studied the electrophysiological properties of insulin-producing cells.
The electrophysiology of insulin-secreting cells
The increase in diabetic prevalence has serious socioeconomic implications, and the relevant costs often exceed 10 % of a country's total health care budget. In non-diabetic individuals, in response to a sudden elevation in glucose levels, insulin is secreted in two phases. The first one occurs within 5–10 minutes and is followed by a sustained or rising second phase of secretion. Patients with type 2 diabetes do not present the first phase of insulin secretion, indicating the medical importance of insulin regulation.

Aiming to delineate the mechanisms behind this biphasic secretion of insulin, scientists of the EU-funded HCSP IN BETA-CELLS project concentrated on pancreatic beta cells, the only cells that produce insulin. These cells store insulin in granules and, following chemical and electrical stimuli, release it through exocytosis. It has been suggested that the biphasic insulin secretion results from the depletion of a readily releasable pool (RRP) of granules.

Using the patch clamp electrophysiology technique, scientists studied calcium channels in pancreatic beta cells, and specifically the dynamics of calcium-mediated exocytosis of insulin. They combined modelling and experimental data to show that insulin secretion occurs in response to a minimal calcium influx and that the RRP granules seem to be located far away from calcium channels.

To translate their findings in human pancreatic beta cells, scientists developed mathematical models for exocytosis and electrical activity. Similarly to what had been observed in mouse cells, the secretory granules in human beta cells were located away from calcium channels and their electrophysiological properties allowed electrical activity. Coupled with calcium imaging, these results could help scientists elucidate the mechanisms of beta cell activation and insulin release.

Taken together, the novel information on insulin granules in human beta cells and the developed tools and models for analysing exocytosis lay the ground for future investigations on the mechanism of defective insulin secretion. Long term, this could lead to the development of new pharmacological treatments for diabetes.

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