With more than half of the patients with cystic fibrosis developing diabetes and most of them exhibiting insulin insufficiency, researchers at the Chinese University of Hong Kong conducted a study to explain this relationship and suggest a potential treatment strategy for CF-related Diabetes.
The study, published this month in the journal Nature Communications, identified cystic fibrosis transmembrane conductance regulator (CFTR) as a regulator of glucose-dependent electrical acitivities and insulin secretion in β-cells.
After testing mice, researchers demonstrated that inhibitors or knockdown of CFTR eliminate, reduce, or significantly attenuate glucose elicited whole-cell currents, membrane depolarization, electrical bursts or action potentials, Ca2+ oscillations, and insulin secretion.
Results revealed a previously unrecognized contribution of CFTR to the electrophysiological properties of pancreatic β-cells, which are fundamentally important for insulin secretion. According to study, CFTR appears to mediate the Cl− efflux, maintaining the resting membrane potential at a level less hyperpolarized than that if the membrane potential is entirely determined by adenosine triphosphate (ATP)-sensitive K+ channels (KATP).
Furthermore, results suggest that CFTR can be further activated by glucose, with Cl− efflux, affecting the glucose-induced membrane depolarization and bursting action potentials, both in magnitude and frequency, which are coupled to Ca2+ oscillations and subsequently insulin secretion.
Although it remains unresolved whether CFTR is directly gated by glucose-induced ATP changes, or by glucose-dependent kinases, these findings shed light on the origin of CFRD and possibly other idiopathic diabetes. Ultimately, results suggest that an experimental drug for the treatment of cystic fibrosis restores normal function of β-cells with this mutation, a finding that may lead to a potential treatment strategy for cystic fibrosis associated diabetes.
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