In type 2 diabetes, the level of sugar in the blood rises because the cells of the body are no longer sensitive enough to insulin, or because the pancreas produces insufficient insulin. Scientists from the Max Planck Institute for Heart and Lung Research in Bad Nauheim have now discovered that FFA2 and FFA3 receptors inhibit insulin secretion. These receptors are activated by acetic acid, which is formed by the insulin-producing cells of the pancreas, among others. This enables the pancreas to prevent the production of too much insulin, and the corresponding excessive drop in blood sugar levels. As acetate is primarily formed in the presence of normal or high blood sugar, acetate receptor inhibitors do not boost insulin production when blood sugar is low. This fact may help prevent dangerous hypoglycaemia in the treatment of diabetes.
The primary cause of type 2 diabetes was long held to be a reduced sensitivity of the body cells to insulin. In recent years, however, it has become clear that already in the early stages of type 2 diabetes insulin secretion is also impaired.
Insulin is produced in pancreatic cells and ensures that body cells can absorb glucose from the blood, thereby reducing blood sugar levels. One trigger for the secretion of insulin is the increase in blood glucose after a meal. Other substances apart from glucose can also function as inhibitors or boosters by acting on the receptors responsible for regulating insulin secretion.
The scientists have now identified receptors in the insulin-producing cells of mice and humans, which can inhibit the secretion of insulin. “When a cell absorbs glucose, it produces acetic acid. This activates the FFA2 and FFA3 receptors and thus inhibits insulin production”, says Cong Tang from the Max Planck Institute for Heart and Lung Research. By contrast, mouse cells without FFA2 and FFA3 receptors secrete more insulin. It seems that the function of the receptors is to prevent too much insulin being produced following an increase in glucose concentrations.
The scientists hope that these findings will lead to new treatment options for diabetes patients. Their next goal is to investigate the development of substances to block the acetate receptors. “The fact that acetate is primarily formed in high-sugar environments makes acetate receptor inhibitors a really attractive focus for research. This means that these substances would take effect only in patients with elevated blood sugar, but not in healthy subjects or well managed type 2 diabetes”, explains Stefan Offermanns, Director of the Department of Pharmacology at the Max Planck Institute.
Prof. Dr. Stefan Offermanns