Yale Researchers Discover Glucose ‘Control Switch’ Linked to Diabetes

Researchers Pinpoint Glucose Control Switch That is Key to Diabetes

Yale School of Medicine researchers have discovered that the prolyl endopeptidase enzyme is key to sensing glucose levels in the blood, linking it to both type 1 and type 2 diabetes.

Researchers at Yale School of Medicine have pinpointed a mechanism in part of the brain that is key to sensing glucose levels in the blood, linking it to both type 1 and type 2 diabetes. The findings are published in the July 28 issue of Proceedings of the National Academies of Sciences.

“We’ve discovered that the prolyl endopeptidase enzyme — located in a part of the hypothalamus known as the ventromedial nucleus — sets a series of steps in motion that control glucose levels in the blood,” said lead author Sabrina Diano, professor in the Departments of Obstetrics, Gynecology & Reproductive Sciences, Comparative Medicine, and Neurobiology at Yale School of Medicine. “Our findings could eventually lead to new treatments for diabetes.”

The ventromedial nucleus contains cells that are glucose sensors. To understand the role of prolyl endopeptidase in this part of the brain, the team used mice that were genetically engineered with low levels of this enzyme. They found that in absence of this enzyme, mice had high levels of glucose in the blood and became diabetic.

Diano and her team discovered that this enzyme is important because it makes the neurons in this part of the brain sensitive to glucose. The neurons sense the increase in glucose levels and then tell the pancreas to release insulin, which is the hormone that maintains a steady level of glucose in the blood, preventing diabetes.

“Because of the low levels of endopeptidase, the neurons were no longer sensitive to increased glucose levels and could not control the release of insulin from the pancreas, and the mice developed diabetes.” said Diano, who is also a member of the Yale Program in Integrative Cell Signaling and Neurobiology of Metabolism.

Diano said the next step in this research is to identify the targets of this enzyme by understanding how the enzyme makes the neurons sense changes in glucose levels. “If we succeed in doing this, we could be able to regulate the secretion of insulin, and be able to prevent and treat type 2 diabetes,” she said.

Other authors on the study include Jung Dae Kim, Chitoku Toda, Giuseppe, D’Agostino, Caroline J. Zeiss, Ralph J. DiLeone, John D. Ellsworth, Richard G. Kibbey*, Owen Chan, Brandon K. Harvey, Christopher T. Richie, Mari Savolainen, Timo Myöhännen, and Jin Kwon Jeong.

The study was funded by the National Institutes of Health (DK084065 and DK097566), and the American Diabetes Association.

Publication: Jung Dae Kim, et al., “Hypothalamic prolyl endopeptidase (PREP) regulates pancreatic insulin and glucagon secretion in mice,” PNAS, 2014; doi:10.1073/pnas.1406000111

Image: Patrick Lynch

1 Comment on "Yale Researchers Discover Glucose ‘Control Switch’ Linked to Diabetes"

  1. Madanagopal.V.C. | July 31, 2014 at 5:53 am | Reply

    Prolyl endopeptidase enzyme— located in a part of the hypothalamus known as the ventro-medial nucleus, is found to be Glucose sensor of the Brain which will trigger insulin release by pancreas. If the blood level is high with Glucose after eating, we generally presume that Beta Cells will sense them and start the production and storage and later on release the protein peptide called insulin. But here comes the master regulator which measures the glucose level through endopeptidase enzyme which it produces. When this machine faults,particularly in age related diabetes, DM-2, this enzyme also seems to be depleted thereby blood becoming more with glucose molecules and diabetic. An enzyme like this if increased by medicines, will supplant the treatment of Diabetes. So far Glucose receptor cells of the body becoming non-active had been attended to by giving Sulphonyl Urea Drugs to shut off K channels and open Calcium channels , thereby allowing insulin in the cell storage to get released. Similarly the drug vildagliptin is used to increase the action of incretins to sustain insulin secretion. The endopeptidase enzyme treatment should be the third medicine in action if successfully employed. BY the by, aging makes every enzyme and hormone to go down in production and activity like dopamine neurotransmitter and many other hormones,which are useful isn’t it? But, adrenaline and other harmful neurotransmitters are increasingly produced as one ages, to get BP, CAD etc in course of time. Aging happens not only in muscle tones but also in the proteins and enzymes of the body. Thank You.

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