“Insulin release is dependent on a complex chain of chemical and electric processes. Until now it has been unknown that ClC3 plays an important role in making this function properly” states Erik Renström, professor of experimental endocrinology and responsible author of the article.
The origin of the finding is a follow up of a previous study on what happens inside the beta cell, on a molecular level, when insulin secretion is stimulated by the diabetes drug Glibenklamid.
“That was when we got our eyes on ClC3, a protein that transports chloride” says Erik Renström. “We were wondering if ClC3 could explain some of the mechanisms behind the action of Glibenklamid, which our group has previously published in the journal Science.”
The next question was how the protein ClC3 acts in the insulin secretion process. In the new article the research group presents their experiments where normal mice, controls, have been compared to knock-out mice that lack ClC3 receptors. These experiments have unraveled the role of the protein both on the level of the single cell and in living mice.
“The capacity to secrete insulin is reduced by 67% in the knock-out mice compared to the control mice. The ClC3 protein regulates the acidity in the beta cell and a low pH is a prerequisite for production and release of insulin” says Dia-Qing Li, researcher at LUDC and the University of Tianjin, China, and the main author of the article.
The knock-out mice have as many, as large and as insulin filled beta cells as the control mice, which shows that it is the mechanism underlying the secretion that fails. When insulin secretion was stimulated using sugar, control mice had a normal response with increased insulin release, whereas knock-out mice had not.
A similar thing was observed when the mice were treated with Glibenklamid. The diabetes drug had no effect on the knock-out mice.
“We don’t know if patients with type 2 diabetes have a lack of ClC3 protein and if that could be one of the reasons behind the disease. We don’t know how the medicine Glibenklamid would work in that case but these are hypotheses worth investigating” says Erik Renström and adds:
“We work with basic science. Our job is to find why the cell fails in diabetes.”
For more information: Erik Renström, tel. nr. 040-39 11 57,
Erik [dot] Renstr%C3%B6m [at] med [dot] lu [dot] se (Erik.Renström[at]med[dot]lu[dot]se)