Researchers at Vanderbilt University Medical Center have received more than $11 million in new grant support aimed at slowing the growing burden of diabetes.
The central theme and unifying focus of two grants from the National Institutes of Health (NIH) and one from the Juvenile Diabetes Research Foundation (JDRF) is to improve understanding of changes that occur in the human pancreatic islet in type 1 and type 2 diabetes.
In both types of diabetes, the insulin-producing beta cells in the pancreatic islet are either destroyed or become dysfunctional, leading to insulin deficiency.
“A unique aspect of this collaborative research is to analyze both pancreatic sections and isolated islets using emerging molecular technologies that have never before been used to study the human pancreas,” said Alvin Powers, M.D., Joe C. Davis Professor of Biomedical Science and director of the Vanderbilt Diabetes Center.
According to the U.S. Centers for Disease Control and Prevention, the number of newly diagnosed cases of diabetes among adults in the United States has more than tripled in the past three decades, from 493,000 cases in 1980 to more than 1.4 million in 2013.
One new grant from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) of the NIH (grant number DK106755) will provide $6.2 million over five years to discover “pancreatic islet signatures” in type 2 diabetes.
Type 2 diabetes is characterized by insulin resistance, in which body tissues do not respond properly to insulin. But central to the development of the disease is impaired insulin secretion by the pancreatic islet.
A multi-disciplinary research team will use techniques such as imaging mass spectrometry, tissue clearing technology and in situ hybridization to study human islets from individuals with type 2 diabetes.
Understanding how beta cell dysfunction occurs could lead to new treatments for the disease.
Powers is the contact principal investigator (PI) of the grant. Other Vanderbilt investigators are Marcela Brissova, Ph.D., Roland Stein, Ph.D., Richard Caprioli, Ph.D., Jeremy Norris, Ph.D., Chunhua Dai, M.D., and Bing Zhang, Ph.D.
Stein is the Mark Collie Professor of Diabetes Research. Caprioli is the Stanford Moore Professor of Biochemistry and director of the Mass Spectrometry Research Center, where imaging mass spectrometry was developed.
With Norris, research associate professor of Biochemistry, and Boone Prentice, Ph.D., a postdoctoral fellow in his lab, Caprioli is using the technology to study lipids and other metabolites in the human islet.
California Institute of Technology investigators Long Cai, Ph.D., and Viviana Gradinaru, Ph.D., also are contributing to the research.
A second NIDDK grant (DK108120) will provide $4.4 million over five years to study the maturation of the human pancreas during the first five years of life.
The goal is to better understand the molecular and cellular changes in the islet during this time period that may give rise to the autoimmune process leading to type 1 diabetes.
Christopher Wright, D.Phil., the Louise B. McGavock Professor and professor of Cell and Developmental Biology, is the grant’s contact PI.
Co-principal investigators are Powers at Vanderbilt and Cai and Gradinaru from Caltech. Co-investigators from Vanderbilt include Brissova, Caprioli, Norris, and Dai.
A companion grant from NIDDK (DK104211), awarded in 2014, supports investigations of molecular mechanisms of beta cell growth in the juvenile human pancreas. Understanding signaling pathways that stimulate growth in the young pancreas could lead to ways to stimulate growth of adult human beta cells.
Powers is contact PI, and Brissova and Dai are Vanderbilt co-investigators. Co-principal investigators are Stanford University’s Seung Kim, M.D., Ph.D., and Andrew Stewart, M.D., director of the Diabetes, Obesity and Metabolism Institute at Mt. Sinai’s Icahn School of Medicine in New York.
Both grants are part of a new NIDDK initiative, the Human Islet Research Network (HIRN).
Vanderbilt is among 40 institutions in five countries participating in HIRN, which is organized into 22 different research projects and four consortia focused on different aspects of beta cell biology and type 1 diabetes.
The new JDRF grant will provide $500,000 over two years to study glucagon-producing alpha cells in the islets of individuals with type 1 diabetes. Disordered glucagon secretion in type 1 diabetes makes these patients susceptible to hypoglycemia. Powers is the PI; Brissova, Stein, and Dai are co-investigators.
Powers said the three grants reflect Vanderbilt’s long-standing research expertise in diabetes, pancreas and islet biology, as well as mass spectrometry.
“We hope these grants will provide new insight into what causes the insulin deficiency in both type 1 and type 2 diabetes and help us understand how to prevent or better treat diabetes,” he said.
