A team of the Department of Morphology of the University of Geneva's Medical School, lead by Prof. Paolo Meda, reported a novel mechanism that could account for the development of type II diabetes, the most common form ß cells - the cells which produce insulin- that cannot release sufficient amounts of this hormone to control blood glucose levels. The Geneva scientists have observed that altering the communication between ß cells, which normally function in coordination, lead to a loss of their normal regulation evidenced by their inability to respond to an elevation of glucose levels. These provide novel insights for the development of new treatments. The results of the Geneva team will be published in the next issue of the Journal of clinical investigation, due July 15, 2000.

The findings of Prof. Paolo Meda's team, which will be published in the July issue of the prestigious Journal of clinical investigation, represent a significant change in the field of diabetes research. Alike many other scientists, those of the University of Geneva are searching for the causes of type II diabetes, which represents 95% of the cases of this disease. However, and at variance with the usual trend of research in this field which has searched for defects at the levels of individual cells, the Geneva scientists have focussed on defects of the mechanism coordinating multiple ß cells during insulin secretion.

The first finding of the Geneva team was that normal cells loose their major properties, and in particular the ability to secrete insulin in response to an increase in glucose, when cell-to-cell communication is altered. Using techniques of molecular biology, the Geneva scientists induced mice to produce a connexin, a protein which forms channels that physically link adjacent cells and allow for cell-to-cell exchanges of signals (there are at least 15 different types of connexins). The scientists then observed that this production lead to an increase in the communication between ß cells which, in parallel, loose their ability to respond to an increase in glucose. The Geneva group also observed that, as a result of these alterations, mice became intolerant to glucose, a major landmark of diabetes.

The findings indicate that type II diabetes may result from an excess, a loss, or a genetic mutation of connexins. In this perspective, the group of Prof. Meda is now extending its research on a connexin specifically produced by ß cells, which the group just discovered, as well as to tissues of diabetic patients. If the hypothesis that diabetes results from an alteration in cell-to-cell communication is validated, the next step will be to develop novel technical approaches aimed at correcting defects in connexins.

References: Junctional communication of pancreatic b-cells contributes to the in vivo control of insulin secretion and glucose tolerance, Anne Charollais 1, Asllan Gjinovci 2, Joachim Huarte 1, Juliette Bauquis 1, Angel Nadal 3, Franz Martín 3, Etelvina Andreu 3, Juan V. Sánchez-Andrés 3, Alessandra Calabrese 1, Domenico Bosco 1, Bernat Soria 3, Claes B. Wollheim 2, Pedro L. Herrera 1, and Paolo Meda 1, Journal of clinical investigation, 15th of July 2000

By injecting a fluorescent molecule into a cell, it is possible to detect the communications taking place between the different cells by the connexin canal since they become fluorescent as well.

On the left, one clearly observes this normal phonomenon of communication between the beta cells. On the right, however, when the injection takes place in an isolated zone of a transgenetic mouse, a fluorescent molecule colours a much larger portion of this organ, indicating that the cells which no longer secrete insulin normally, communicate between themselves in an exaggerated manner.

For further information, please contact:
Paolo Meda, phone 0041 22 702 52 10