A new Joslin Diabetes Center-led study has shown conclusively that two receptors in the insulin-producing beta cell do not affect developmental growth, refuting a long-held hypothesis in diabetes research.
This finding is helping scientists in their efforts to isolate the growth factors that do stimulate beta cell growth and understand the defects in insulin production and secretion that cause diabetes.
These two receptors have been a major focus of research on beta cell development as scientists seek to find ways to promote the growth of these essential insulin-producing cells in diabetes patients. This latest research will appear in an upcoming issue of Nature Genetics.
In two previous Joslin studies, insulin receptor, a protein that mediates the action of insulin, and the receptor for insulin-like growth factor I (IGF-I), a hormone, which were suggested as critical for mediating islet/beta cell development and growth, were individually "knocked out" in beta cells in genetically altered mice. Researchers were surprised to discover that the beta cells developed and grew normally without these receptors, according to Rohit N. Kulkarni, M.D., Ph.D., Investigator at Joslin Diabetes Center and Assistant Professor of Medicine at Harvard Medical School, who led the latest study and was lead author in the two previous Joslin studies.
"When you knock out one receptor at a time, the remaining receptor can compensate for the other since both are so similar," says Dr. Kulkarni. "In this study, we knocked out both at the same time and still didn't see a defect in the developmental growth of beta cells. Our conclusion is that there are growth factors and pathways independent of IGF-I and insulin that are necessary for the development of beta cells."
Beta cell function, or lack of it, is critical in both type 1 and type 2 diabetes. Type 1 diabetes occurs when the beta cells in the pancreas are attacked by a malfunctioning immune system, while in type 2 diabetes, the beta cells function but do not produce enough insulin to meet the body's needs or do not respond appropriately to the insulin that is produced. Long viewed as an autoimmune disease, type 1 diabetes may instead be caused by an underlying dysfunction in insulin/IGF-I signaling and increased vulnerability of beta cells to stress during the weaning period, a hypothesis currently being investigated by Dr. Kulkarni's laboratory. Recent research suggests that type 2 diabetes includes a variety of diseases caused by multiple defects in the insulin-production, insulin-signaling and insulin-using system.