Discovery of insulin-production method could impact multiple fields
Researchers with the University of Houston Cullen College of Engineering have made a major discovery in the field of diabetes research that is also an historic find in the area crystal formation and use.
Peter Vekilov, associate professor of chemical engineering, and doctoral candidate Dimitra Georgiou, discovered a new mechanism for the formation of insulin crystals in the pancreas.
While the finding will play a significant role in gaining a better understanding of diabetes, it is also only the third mechanism of crystal formation ever discovered. The finding is significant enough, in fact, to be showcased in the February 7th issue of Proceedings of the National Academy of Sciences, one of the world’s leading scientific journals.
Since insufficient insulin production in the pancreas is one of the primary causes of adult-onset diabetes, Vekilov and Georgiou are studying the process of how insulin is produced in the first place. Understanding how the body creates this hormone, Vekilov said, will make it easier for researchers to discover why some individuals do not produce enough insulin and thus develop diabetes.
Specifically, the two have focused on the creation of insulin crystals, the form in which insulin is stored in the pancreas before it is released in the bloodstream.
“It is possible that the insulin deficiency happens when the crystals don’t form properly and then part of the insulin that is produced gets destroyed,” Vekilov said.
It has long been known that proinsulin, a molecular precursor to insulin itself, is the basis of these crystals. After an insulin molecule is produced from proinsulin, it attaches to an insulin crystal only in special locations where other insulin molecules have formed right angles, called kinks.
Thousands of block-shaped insulin molecules, each measuring 5 nanometers apiece, attach themselves to crystals in special locations known as kinks. Vekilov and Georgiou found that groups of insulin blocks form mounds, resulting in the creation of multiple kinks. These additional kinks provided by the mounds allow for rapid growth of insulin crystals.
Using atomic force microscopy, Vekilov and Georgiou discovered a new mechanism by which insulin molecules attach themselves to crystals to form these kinks. Groups of insulin blocks, they found, create large protrusions, dubbed mounds by Vekilov and Georgiou. The very nature of these mounds results in the creation of multiple kinks—far more, in fact, than the other methods of kink formation.
By providing so many spaces where insulin molecules can attach to an insulin crystal, mounds allow for the rapid growth of that crystal.
Interestingly, these mounds only form when there is a surplus of insulin that allows for rapid crystal growth. This is noteworthy because, in addition to growing at kinks, insulin crystals dissolve at kinks, as well. Since no mounds appear when there is a lack of insulin, mounds are, in effect, important sources of a crystal’s net growth.
“Typically in nature, [a mechanism that enables] fast growth also results in fast dissolution,” said Vekilov. “But this process cheats physics because when there isn’t a lot of insulin, mounds don’t form. It’s an asymmetric mechanism.”
While this discovery is important to the field of diabetes research, it should also have a major impact on the study of crystal formation. Before this finding there were only two known ways that crystals grew. The first was proposed in the 1870s by Josiah Willard Gibbs, the father of modern physical chemistry and the first person to receive a doctorate in engineering in the United States. Russian Physicist V.V. Voronkov proposed the second mechanism in 1968. This is the only the third mechanism ever discovered.
It is possible, said Vekilov, that crystals composed of materials other than insulin also grow in this manner. If so, this discovery could significantly impact any number of fields that deal with crystals.
“This is a new mechanism of crystal growth, which can help us understand all processes of crystal formation including semiconductor and optical materials, geological crystallization, ice formation, and the physiological and pathological crystallization of proteins and small molecules,” said Vekilov.
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