Uppsala: New light on mechanisms behind insulin release

Research lead

Scientists at Uppsala University, Sweden, have shed new light on the processes that determine the release of the blood sugar–lowering hormone insulin, using image analysis methods that make possible the detailed study of events immediately inside the plasma membrane of the insulin-secreting cells.

Cyclic AMP (cAMP) is a universal messenger molecule that controls a number of different functions inside the cell, including playing a role in the release of insulin from the beta cells in the pancreas.

It is known that the production of cAMP can influence certain hormones to amplify insulin secretion. But it has been unclear to what extent cAMP prompts the major release of insulin that is triggered by an increase in blood sugar.

Anders Tengholm and his research team at Uppsala University have developed methods that make it possible for the first time to measure both the secretion of insulin and the cAMP concentration in individual beta cells. The results show that ATP, the cellular energy source that is generated when glucose is metabolised, causes an increase in cAMP concentration at the cell membrane, where the release of insulin takes place.

This increase varies rhythmically and coincides with similarly regular variations in another stimulant messenger, the calcium ion, resulting in pulsatile secretion of insulin.

Optimal glucose-induced insulin secretion requires that the varying cAMP

and calcium signals are coordinated in time. The study provides new understanding of the cellular mechanisms that underlie the pulsatile release of insulin in healthy individuals, claims Tengholm.

The discovery that the cell metabolism directly stimulates the production of cAMP provides a new approach for the regulation of this molecule. The connection between metabolism and cAMP is not only important for the secretion of insulin, it also plays a role in gene regulation, cell growth, and cell survival.

The researchers say their observations pave the way for understanding of the disturbed beta cell function in Type II diabetes, and for the development of new drugs for the disease.