A cell-signaling pathway that plays a key role in increasing insulin secretion during pregnancy has been identified by scientists. They also revealed that when blocked, this pathway leads to the development of gestational diabetes. During pregnancy, pancreatic beta cells should expand and produce more insulin to adapt to the needs of the growing baby, explained senior investigator Adolfo Garcia-Ocana, Ph.D., associate professor of medicine, Division of Endocrinology and Metabolism, University of Pittsburgh School of Medicine.
Newborns can suffer complications if the mother's blood glucose is abnormally high during pregnancy, a condition known as gestational diabetes.
"Not much was known about the maternal mechanisms that lead to increased beta cell number and function during pregnancy," Dr. Garcia-Ocana said.
"But research has shown that high blood glucose in pregnancy can have long-term health consequences for the child, as well as a greater risk of hypertension, type 2 diabetes, and high cholesterol for the mother," he noted.
His team began studying a protein called hepatocyte growth factor (HGF), which was discovered by George K. Michalopoulos, M.D., Ph.D., professor and chair, Department of Pathology, Pitt School of Medicine, in 1990.
Blood levels of HGF are markedly increased in pregnancy. The protein interacts with a cell surface receptor called c-MET.
"Mice that didn't have the c-MET receptor in their pancreas had lower plasma insulin levels, higher blood glucose and impaired ability to regulate glucose levels. Without the receptor, they couldn't respond to HGF," Dr. Garcia-Ocana said.
"These findings provide the first direct evidence that HGF/C-MET signaling pathway has an important role in maternal beta cell adaptation during pregnancy," Dr. Garcia-Ocana noted.
"Perhaps women who have a variation in the HGF gene or in the c-MET receptor are predisposed to developing gestational diabetes because they cannot adequately compensate for the increased insulin demands of pregnancy," he stated.
In future work, he and his team will explore HGF signaling in pregnant women, which could one day provide a new means of diagnosing, treating or preventing gestational diabetes.
Their findings are available online today in Diabetes, one of the journals of the American Diabetes Association.