Many researchers are pursing treatment options for diabetes­­—a disease characterized by high glucose levels— through approaches that increase insulin. However, there are two pancreatic hormones that play a critical role in regulating glucose levels, insulin, produced by pancreatic beta cells, lowers glucose and glucagon, produced by pancreatic alpha cells, increases circulating glucose levels.

Yet, the factors that regulate glucagon secretion from alpha cells are still not fully understood.

The UAB Comprehensive Diabetes Center (UCDC) has had a keen interest in studying a specific protein: thioredoxin-interacting protein (TXNIP) as one of its lines of investigation into curative diabetes treatments. Indeed, when TXNIP expression is inhibited or deleted, glucose control in animal models with diabetes and in human subjects with type 1 diabetes improved.

In fact, UCDC Director Anath Shalev, M.D., in a 2014 review of TXNIP, notes that TXNIP deficiency protects against type 1 and type 2 diabetes by promoting beta-cell survival and function.

However, while TXNIP knockout has been well-researched in pancreatic beta cells, it has not been investigated in pancreatic alpha cells. So, the Shalev Lab set out to explore TXNIP knockout in alpha cells and the results were just published in a paper entitled “Alpha cell TXNIP deletion improves diabetes-associated hyperglycemia and hyperglucagonemia” in the peer-reviewed journal Endocrinology.

The team of researchers found that when diabetic mice had their TXNIP knocked out in pancreatic alpha cells (aTKO), they showed improvement in glucose tolerance and lower blood glucose levels compared to their control littermates. While no changes in insulin were observed, the diabetes-associated increase in glucagon was blunted in these mice and glucagon secretion from aTKO islets was significantly reduced.

Thus, the researchers concluded that downregulation of alpha cell TXNIP is associated with reduced glucagon secretion and that this may contribute to the glucose-lowering effects observed in diabetic aTKO mice.

The studies thereby shed new light onto the regulation of glucagon secretion and the role of TXNIP in non-beta cells, providing critical information for the development of novel treatment approaches to better regulate glucose control in those affected by diabetes.