New findings about messenger molecule raise hopes for new drug

Uppsala University scientists have developed a new method for measuring the concentration of the messenger substance for cells, cyclic adenosine monophosphate (cAMP), in individual living cells.

Thanks to this method, the researchers have been able to see how the same messenger molecule can regulate disparate cell functions. The findings will probably be of great value in the development of new drugs for diabetes, among other diseases. The study is being published in the scientific journal Nature on January 19.

Cyclic adenosine monophosphate (cAMP) is a messenger molecule that transmits signals from the cell surface to govern a number of different functions inside the cell. cAMP is vital for the regulation of metabolism, ion channel activity, secretion, and genetic expression, for instance. In insulin-producing cells cAMP serves as a powerful booster of insulin release.

Four Uppsala researchers have developed a new method that makes it possible to measure the concentration of cAMP in individual living cells. With the new method the scientists have studied insulin-producing cells and found that stimulation with hormones leads to regular variations in the concentration of cAMP.

The scientists have also seen that the frequency of the variations in concentration gives rise to different signals. Short-lived increases in concentration were sufficient to activate calcium ion channels, while a stable increase in concentration was necessary for a cAMP-activated protein to enter the cell nucleus and regulate the expression of genes.

- The pattern of concentration changes thus determines what information the messenger molecule is to convey. In this way, the same messenger substance can regulate disparate cell functions. It has never been demonstrated before that this is how cAMP works, says Anders Tengholm, who leads the study.

The Uppsala study enhances our understanding of the signals that regulate the release of insulin. This is a key finding for diabetes research, since this release is disturbed in patients with type-II diabetes.

The new method will be of great value in the mapping of many cAMP-regulated processes in various types of cells.

- The new ability to measure cAMP will probably facilitate the development of new drugs not only for diabetes but also for disorders of the heart, nervous system, and certain forms of cancer, says Anders Tengholm

The findings are being published in the journal Nature on January 19. Co-authors are Oleg Dyachok, Yegor Isakov, and Jenny Sagetorp.