Gut Hormone Shows Potential for Lowering Insulin Levels

A novel function of a hormone in the gut may be a potential new way to lower glucose levels in diabetes patients, researchers at the Toronto General Research Institute and the University of Toronto have found.

By activating receptors on the cholecystokinin (CCK) peptide hormone in the gut, Dr. Tony Lam, the John Kitson McIvor Chair in Diabetes Research at theToronto General Research Institute and University of Toronto, and assistant professor in the Departments of Physiology and Medicine at the University of Toronto, and his team of researchers were able to “rapidly and potently” lower blood glucose levels. Activation of the CCK hormone triggered a signal in the brain that was then sent to the liver to lower the production of glucose. In the course of the same experiment, the researchers found that in rats who were fed a high-fat diet for three days, CCK was unable to lower blood sugar levels.

Published in Cell Metabolism, the study indicates that “a primary increase of CCK-8, the biologically active form of CCK, in the duodenum lowers glucose production independent of changes in circulating insulin levels.” The authors also state that, in regard to the brain’s participation in the lowering of the glucose level, “duodenal CCK-8 requires the activation of the gut CCK-A receptor and a gut-brain-liver neuronal axis to lower glucose production.”

"Our findings reveal a novel role for the CCK hormone and suggest that CCK-resistance in the gut may contribute to high blood sugar levels in response to high-fat feeding in rodents. Understanding how to overcome CCK-resistance in the gut so that blood sugars can be lowered could be a novel therapeutic approach to diabetes and obesity," said Lam. “"This paper complements our study that was published last year in Nature indicating that in the future, we may be able to design a drug to target the gut to lower glucose levels in patients with diabetes."

Lam also said that, while the study findings are promising, “the clinical therapeutic implications of the current findings remain largely unknown,” and “a large amount of time will be required to determine whether enhancing CCK action in the gut of humans is effective and safe in lowering glucose levels.”