Sushant Bhatnagar, Ph.D., an associate professor in the Division of Endocrinology, Diabetes and MetabolismResearchers at the University of Alabama at Birmingham have identified a protein that helps balance insulin secretion and growth in pancreatic beta cells, a discovery that could help guide future strategies to restore beta cell function in diabetes.
Pancreatic beta cells are cells that produce insulin, the hormone responsible for regulating blood glucose levels. Diabetes develops when beta cells can no longer produce or secrete enough insulin to meet the body’s needs, because the beta cells become dysfunctional, their mass declines or both.
In a preclinical study, UAB researchers discovered that the protein Tomosyn-2 plays a key role in regulating postnatal beta cell growth and insulin secretion to maintain glucose homeostasis. The findings provide new insight into how beta cells balance growth with functional maturation during early life and may have implications for Type 1 and Type 2 diabetes.
The study was led by Sushant Bhatnagar, Ph.D., an associate professor in the Division of Endocrinology, Diabetes and Metabolism. The first co-authors are Katherine Perez and Justin Alexander, researchers in the Bhatnagar lab in the UAB Comprehensive Diabetes Center.
Investigating the role of Tomosyn-2 in beta cell development
Beta cell development begins before birth, but these cells continue to expand and mature throughout infancy and adulthood. Although adults retain a limited ability to generate new beta cells, that capacity declines sharply with age, making recovery from beta cell loss in diabetes particularly difficult.
Researchers investigated whether Tomosyn-2 regulates the transition from beta cell expansion to functional maturation.
Katherine Perez and Justin Alexander
“What drew us to Tomosyn-2 was the possibility that it regulates insulin secretion and also influence how beta cells develop and mature after birth,” Bhatnagar said. “Because beta cells must balance two important processes — increasing in number while also acquiring mature insulin-secretory function — we wanted to understand whether Tomosyn-2 helps coordinate that balance.”
Researchers used a Tomosyn-2 loss-of-function animal model to define the physiological role of the protein in vivo. The model allowed investigators to examine how loss of Tomyosyn-2 affects insulin secretion, beta cell proliferation, beta cell mass and glucose homeostasis from early postnatal life into adulthood.
Enhanced insulin secretion accompanied by reduced beta cell expansion
The researchers found that loss of Tomosyn-2 enhanced insulin secretion and improved glucose control, suggesting that Tomosyn-2 normally functions as a “molecular break” on insulin release.
At the same time, the researchers discovered an important biological trade-off. While beta cells lacking Tomosyn-2 became more functionally mature, they showed reduced growth proliferation and limited beta cell mass expansion.
The findings suggest that Tomosyn-2 helps coordinate the balance between beta cell growth and functional maturation. This balance is critical because beta cells must both expand early in life and maintain sufficient insulin-secretory capacity throughout adulthood.
Although the team anticipated that loss of Tomosyn-2 would enhance insulin secretion, they did not expect the increase in beta cell function to be accompanied by reduced beta cell expansion.
“That finding revealed a much broader role for Tomosyn-2 than we initially anticipated,” Bhatnagar said. “It suggests that Tomosyn-2 is not simply regulating insulin release at the plasma membrane; it may also be part of a developmental program that determines whether beta cells prioritize growth or mature function.”
The researchers say the findings could help guide future strategies to preserve or restore functional beta cell mass in diabetes.
“Ultimately, we hope to determine whether modulating Tomosyn-2 or related pathways could improve beta cell function without compromising beta cell mass or long-term beta cell health,” Bhatnagar said.
Other contributors to the study, “Tomosyn-2 regulates postnatal beta cell expansion and insulin secretion to maintain glucose homeostasis,” include Mostafizur Rahman, Ph.D.; Yanping Liu, Ph.D.; Jeong-A Kim, Ph.D.; Chad S. Hunter, Ph.D.; and Thanh Nguyen, Ph.D.
The study was paper of the month and cover story in the May 2026 issues of Diabetes, the flagship journal of the American Diabetes Association.