Glucose processing, regulated by insulin, is impaired in diabetics. Unraveling the biochemical basis of this impairment may, in the long term, help scientists find a cure for the condition.
There's more to the story of insulin production by cells than rapid, hightened release of insulin from cells in response to hightened levels of glucose in the blood. There are also naturally-occurring slow rhythms of insulin production within the body.
These rhythms occur in waves of approximately 2 or 24 hour oscillation (i.e., maximum to minimum to maximum levels of release occurring over a 2 or 24 hour period, repetitively). These rhythms are important for maintaining optimal insulin function within the body.
However, much of the details underlying how these insulin rhythms are maintained by cells, and how small molecules (such as fatty acids) regulate wave oscillations, are unknown. This is because there are no techniques available that can rapidly probe insulin waves over a long period of time.
Kendra Reid and Robert Kennedy (University of Michigan) have tackled this challenge. They have developed an automated device that monitors insulin secretion from cells every six seconds for over one day.
Monitoring insulin waves.
The scientists placed a single islet of Langerhans on their device. An islet of Langerhans is a collection of several thousand cells (in the pancreas) that secrete insulin.
They continuously forced a physiological saline solution through their cells. This constant flow kept the cells alive.
They initially started the experiments in a glucose concentration of 3 mM, and then quickly raised it to 11 mM. In all of the experiments, a large initial burst in insulin secretion was observed for roughly 10 or 20 minutes, followed by lower levels of release over the course of hours.
Towards the biological basis of long-duration insulin waves.
These results have been observed by other scientists. A new discovery here is that insulin osciallations did not necesssarily begin right away.
The scientists observed three broadly different results. Three islets gave oscillations of 3-5 minute periods that began after the initial burst and continued throughout the course of the experiment.
Two islets only produced oscillations one hour after the initial insulin burst, and one islet gave no oscillations at all. A large number of experiments will be needed in the future to determine how many cells in a given population will be expected to exhibit immediate oscillations, delayed oscillations, or no oscillations.
More importantly, the scientists found that the longer (2-4 hour) oscillations were comprised of more rapid (4-6 minute) oscillations. This suggests that long-term fluctuations of insulin secretion may be regulated in cells by increasing magnitudes of shorter-term fluctuations.
The biological basis of short-term insulin oscillations is rather well-known. Since it now seems that the place to begin unraveling the unknown biological basis of long-term insulin oscillations lies in biochemistry that is already well-developed, the mystery may be more readily solved than is commonly realized.
These scientists have made steps towards unravel the biochemical basis of long-term insulin secretion, which may in the long term aid in finding a cure for diabetes. In the shorter term, their experimental design will help scientists monitor other long-term processes in individual cells, that are not otherwise addressable without the experimental automation uniquely provided by their device.
for more information:
Reid, K. R., & Kennedy, R. T. (2009). Continuous Operation of Microfabricated Electrophoresis Devices for 24 Hours and Application to Chemical Monitoring of Living Cells Analytical Chemistry, 81 (16), 6837-6842 DOI: 10.1021/ac901114k