Type 2 Diabetes May Result From Deficient Activity by Special Pancreatic Beta-cells

Insulin released by pancreatic beta (β) cells regulates blood glucose levels. If the system fails, it may cause hyperglycemia inducing Type 2 diabetes. But recent research indicates that a specific subset of β cells work like pacemakers and orchestrate insulin release by the pancreas, according to U. K. researchers in the study “Beta Cell Hubs Dictate Pancreatic Islet Responses to Glucose,” published in the journal Cell Metabolism.

In the pancreas, clusters of β cells localize in regions known as islets of Langerhans, and respond rhythmically to high glucose levels.

A subset of β cells was already believed to be a major influence in the islet dynamics and in insulin release. But in the recent study, researchers identified a specific β cell population that works like a hub in propagating calcium waves to connecting distant islet regions. The cells, which researchers called hub cells, were found to express several markers of immature β cells.

For the first time, hub cells were electrically silenced in the living tissue using light, a technique known as optogenetics. Researchers specifically directed the expression of a chloride (Cl⁻) pump (halorhodopsin) to the cells. Upon illumination, chloride ions were pumped into the cell causing cell membrane hyperpolarization. As a result, calcium influx was inhibited and the hub cell function was compromised. The team showed that in animals, activation of the system interferes with glucose sensing and with increased tolerance to glucose levels, probably because of more insulin release.

“By combining large-scale functional cell mapping with optogenetics and photopharmacology, we provide here a revised blueprint for islet function whereby a few pioneer hubs with reduced β cell identity dictate emergent population behavior in response to glucose, “ the authors wrote in the study.

Because inflammation is associated with type 2 diabetes, researchers also investigated the influence of inflammatory stimuli in cell hub response to glucose, and found that it affects both the number of hubs and its connections.

Overall, cell hubs have a high impact in response to glucose and could present a promising therapeutic target for type 2 diabetes patients. The authors concluded: “the present findings provide new insights into the regulation of islet function by individual β cells and the mechanisms that likely target and impair this during type 2 diabetes pathogenesis and treatment.”

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