Mice in which the pancreas cells that produce insulin, or beta cells, lack so-called M3 muscarinic acetylcholine receptors develop some symptoms of diabetes, including impaired glucose tolerance and reduced insulin release, the authors report. M3 receptors are normally on the receiving end of messages relayed by involuntary nerves that indicate the presence of food.
In contrast, mice genetically altered to harbor an excess number of beta cell M3 receptors show the opposite: a profound increase in glucose tolerance and insulin release, the researchers found. Moreover, such animals become resistant to developing symptoms of diabetes or prediabetes when fed a high-fat diet.
The findings suggest that drugs that boost the activity of the M3 receptors on pancreatic beta cells might have therapeutic potential, said Jurgen Wess of the National Institute of Diabetes and Digestive and Kidney Diseases.
"There may be ways to specifically drive up the number of M3 receptors expressed in pancreatic beta cells," Wess said. "It might also be possible to enhance M3 receptor signaling in beta cells by targeting proteins that modulate M3 receptor function in a specific fashion."
Receptors of the same type are also found in other parts of the body, he explained. Therefore, drugs that directly stimulate M3 receptors in general would likely come with problematic side effects--for example, causing smooth muscles to contract.
One of three branches of the involuntary nervous system, the parasympathetic, or "rest and digest" system fulfills many roles--slowing the heart rate, dilating blood vessels, and stimulating digestive secretions.<