B. pilosa has long been purported to have antidiabetes activity, but despite the advancement in phytochemistry and animal models of diabetes, no human clinical trials have been conducted to date. Here, we evaluated the effect of a B. pilosa formulation on fasting blood glucose (FBG), fasting serum insulin, and glycosylated hemoglobin A1c (HbA1c) in diabetic subjects. The B. pilosa formulation reduced the level of FBG and HbA1c in diabetics but increased fasting serum insulin in healthy subjects. Moreover, combination of B. pilosa formulation with antidiabetic drugs had better glycemic control in diabetics. The homeostatic model assessment (HOMA) data suggested that the antidiabetic activity of this formulation was via improvement of β-cell function. We also tested the safety of the B. pilosa formulation in healthy subjects and observed no obvious side effects. We conclude that B. pilosa has potential as an antidiabetes treatment.

Loss of β‐cell number and function is a hallmark of diabetes. β‐cell preservation is emerging as a promising strategy to treat and reverse diabetes. Here, we first found that Pdia4 was primarily expressed in β‐cells. This expression was up‐regulated in β‐cells and blood of mice in response to excess nutrients. Ablation of Pdia4 alleviated diabetes as shown by reduced islet destruction, blood glucose and HbA1c, reactive oxygen species (ROS), and increased insulin secretion in diabetic mice. Strikingly, this ablation alone or in combination with food reduction could fully reverse diabetes. Conversely, overexpression of Pdia4 had the opposite pathophysiological outcomes in the mice. In addition, Pdia4 positively regulated β‐cell death, dysfunction, and ROS production. Mechanistic studies demonstrated that Pdia4 increased ROS content in β‐cells via its action on the pathway of Ndufs3 and p22phox. Finally, we found that 2‐β‐D‐glucopyranosyloxy1‐hydroxytrideca 5,7,9,11‐tetrayne (GHTT), a Pdia4 inhibitor, suppressed diabetic development in diabetic mice. These findings characterize Pdia4 as a crucial regulator of β‐cell pathogenesis and diabetes, suggesting Pdia4 is a novel therapeutic and diagnostic target of diabetes.