Monday September 23, 2013

Glucose-Induced Cyclic AMP Oscillations Regulate Pulsatile Insulin Secretion

Oleg Dyachok, Olof Idevall-Hagren, Jenny Sa getorp, Geng Tian, Anne Wuttke, Ce´ cile Arrieumerlou, Go¨ ran Akusja¨ rvi, Erik Gylfe, and Anders Tengholm*

Cell Metabolism 8, 26–37, July 2008 ª2008 Elsevier Inc.

Background: Insulin secretion from pancreatic beta cells has been coupled with the metabolism of glucose, which has be discovered as a stimulus for insulin release. Through a specific cascade, the degradation of sugar leads to an influx of calcium into the cell and the excretion of insulin secretory granules.  All of these processes seem to happen with an orchestrated oscillation revolving around a wave like pattern of the calcium influx. Another critical messenger for insulin release is cyclic AMP, however until recently kinetics and characterization of this enzyme have been not been feasible so not much is know about its function. Preliminary data found, using newly developed techniques, has revealed oscillation of cAMP triggered by glucose that correspond with increased calcium levels.

Objective: Use the evanescent-wave microscopy technique for real time recordings of cAMP, as well as single-cell recordings of insulin release to study enzyme kinetics of glucose induced cAMP in conjunction with insulin secretion.

Results:

• In mouse derived MIN6 beta cells an increase in glucose was followed by increase of cAMP in oscillating patterns as seen using CFP/YFP florescence. Following this trend, a larger induced glucose concentration revealed a larger coupled cAMP response.
• After the analysis of cAMP oscillations in comparison to glucose induced calcium influxes in MIN6 beta cells it was seen that calcium enhances the increase in glucose induced cAMP but is not essential for this rise.
• In cells containing increased calcium, a correlation was found between cell metabolism and cAMP production where cell metabolism acted as a trigger for cAMP. Researchers confirmed this idea, by increasing ATP levels within the cell using oaubain which also showed an increase in cAMP production.
• Finally, ending studies revealed cAMP oscillations played a key role in the pulsatile secretion of  insulin. For each pulsatile release of insulin from the pancreatic beta cells, a coordinating cAMP oscillation preceded secretion.

-JI