Deficiency of Urokinase Plasminogen Activator May Impair β Cells Regeneration and Insulin Secretion in Type 2 Diabetes Mellitus

Abstract

Background: The relationship between urokinase-type plasminogen activator (uPA) and the development of type 2 diabetes mellitus (T2DM) was investigated in the study by using mice and cell models, as well as patients with T2DM. Methods: In mice models, wild-type and uPA knockout (uPA-/-) BALB/c mice were used for induction of T2DM. In cell models, insulin secretion rate and β cell proliferation were assessed in normal and high glucose after treating uPA siRNA, uPA, or anti-uPA antibody. In our clinical study, patients with T2DM received an oral glucose-tolerance test, and the relationship between uPA and insulin secretion was assessed. Results: Insulin particles and insulin secretion were mildly restored one month after induction in wild-type mice, but not in uPA-/- mice. In cell models, insulin secretion rate and cell proliferation declined in high glucose after uPA silencing either by siRNA or by anti-uPA antibody. After treatment with uPA, β cell proliferation increased in normal glucose. In clinical study, patients with T2DM and higher uPA levels had better ability of insulin secretion than those with lower uPA levels. Conclusion: uPA may play a substantial role in insulin secretion, β cell regeneration, and progressive development of T2DM. Supplementation of uPA might be a novel approach for prevention and treatment of T2DM in the future.

Catharanthus roseus Combined with Ursolic Acid Attenuates Streptozotocin-Induced Diabetes through Insulin Secretion and Glycogen Storage

“…It is assumed that it might be due to the stimulation of beta cell to secrete insulin or it may also be possible due to the regeneration of beta cells of pancreas. Our results corroborate the previously reported research studies of similar kind [30][31][32].…”

Icariin Protects Mouse Insulinoma Min6 Cell Function by Activating the PI3K/AKT Pathway

“…Because reduced insulin release has been reported to be the main symptom during the pathogenesis of T2D [ 21 ], we assessed the effects of ICA on levels of insulin in glucose-treated Min6 cells. We found that ICA significantly and dose-dependently increased high glucose-induced insulin secretion when compared with cells treated with UA alone.…”