Novel Mechanisms Controlling Insulin Release

The research group led by Carlos Ibáñez studies how signaling by growth factors and their receptors regulate different physiological functions in the body. They have recently investigated the functions of one of these receptors, called ALK7, using mutant mice (knock-out mice) lacking this receptor. They found that in the absence of ALK7, mice developed abnormally high levels of insulin in the blood, which with age led to insulin resistance and liver steatosis, a pathological condition in which the liver enlarges and accumulates abnormally high levels of fat.

In collaboration with another research group at Karolinska Institutet, led by Professor Per-Olof Berggren, they also found that Calcium signaling in pancreatic beta-cells was reduced by the actions of the growth factor Activin B through the ALK7 receptor, and that blood glucose levels regulates the expression of both Activin B and ALK7. In agreement with these results, mice lacking Activin B also developed hyperinsulinemia to a similar extent as ALK7 mutants. “In other words, our data revealed an unexpected negative feedback loop in the control of glucose-dependent insulin release, mediated the actions of Activin B on the ALK7 receptor”, says Ibáñez.

In the second study, the scientists found that mice lacking ALK7 accumulated less fat and gained less weight than their normal counterparts when fed on a high-fat diet. They discovered that another growth factor called GDF3 could also signal via the ALK7 receptor, and that mice lacking GDF3 showed similar defects in fat deposition and weight gain as the ALK7 mutants.

Intriguingly, however, mutant mice consumed equal amounts of food as their normal counterparts during the experiment. “These results show that lack of ALK7 or GDF3 improves energy balance in the body under regimes of high caloric intake”, says Ibáñez.

MEDICA.de; Source: Karolinska Institutet