Scientists have long known that defects in the CFTR protein cause cystic fibrosis.
Now they’ve discovered that the defective protein leads to faulty insulin signaling, which, in turn, can cause diabetes and also contribute to cystic fibrosis complications. Insulin is a hormone that regulates metabolism, or the conversion of food to energy.
Interactions between faulty CFTR and insulin play a role in insulin deficiency, Japanese researchers said. This increases the risk of both diabetes and airway infections, they said.
Yoshinori Marunaka, a professor at Kyoto Prefectural University of Medicine, led a review of studies dealing with interactions between CFTR and insulin.
The team’s article, “The Mechanistic Links between Insulin and Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Cl− Channel,” was published in the International Journal of Molecular Sciences.
Diabetes is common in cystic fibrosis patients. Scientists believe it stems in part from fibrotic scarring of the pancreas, the organ that produces insulin.
But Marunaka’s team showed that the reality might be more complex.
Lack of functional CFTR protein in the pancreas, with a resulting imbalance in chloride ions, may make it more difficult for insulin-secreting cells to get insulin through their membranes, researchers said.
In healthy people, glucose — or blood sugar — helps trigger a cell’s release of insulin, with help from ions inside the cell. But when the concentration of chloride ions is abnormal — with a resulting loss of ion balance — the process gets disrupted, impairing insulin secretion.
Meanwhile, research on the lungs has shown that CFTR protein is needed for the cells lining the airways to absorb glucose. Without a functional CFTR protein, insulin is unable to prompt glucose to enter the cells.
The increased sugar content on the cell surfaces offers ideal conditions for bacteria to grow, Marunaka noted.
Normally, insulin also increases what scientists call barrier immunity by strengthening connections among surface cells that prevent microbes from entering the body. This feature also requires the assistance of a functional CFTR protein, however, the review noted.
Marunaka believes that new insights into how CFTR and insulin interact may give researchers clues to developing treatments for cystic fibrosis-related diabetes.