Research yields new insights into the cause of diabetes

The cause of insulin-dependent, permanent, diabetes in newborn babies may be a deficiency in the enzyme Pancreatic Endoplasmic Reticulum Kinase (PERK) during a critical period of development before birth, according to a new hypothesis put forward by a team of researchers from Penn State University. In this most severe type of diabetes, individuals are unable to regulate glucose normally because they have few insulin-producing beta cells in their pancreas and the remaining cells do not produce enough insulin. Using special strains of mice bred to be PERK-deficient, the researchers demonstrated that the lack of this enzyme blocked the proliferation of beta cells, hampered the normal functioning of beta cells, and also kept beta cells from clustering into islets. "What happens during fetal development predisposes people either to be able to maintain glucose levels normally or to have diabetes," says team leader Douglas Cavener, professor and head of the Department of Biology. The research results will be published in the journal Cell Metabolism on 6 December 2006.

The team, consisting of graduate students Wei Zhang, Yulin Li and Kaori Iida, Postdoctoral Fellow Daorong Feng, and Research Assistant Professor Barbara McGrath, made use of the lab's earlier discovery that mice deficient in PERK show many parallels to human sufferers of Walcott-Rallison Syndrome (WRS), in which diabetes is combined with skeletal and growth abnormalities. The research provided an experimental model for investigating the cause of permanent neonatal diabetes that was more revealing than cell culture studies.

"Being able to develop special strains of mice that are PERK-deficient in specific organs or tissues was vital to our research," says Cavener. "These mice allowed us to discover exactly how PERK participates in the development and growth of the beta cells in the pancreas that secrete insulin. Using genetics in this way lets the organism tell you what

Contact: Barbara K. Kennedy
Penn State

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