Abstract
Background Elevated uric acid (UA) has been found to damage pancreatic β-cell, promote oxidative stress, and cause insulin resistance in type 2 diabetes (T2D). Astragaloside IV (AS-IV), a major active monomer extracted from Astragalus membranaceus (Fisch.) Bunge. which belongs to TRIB. Galegeae (Br.) Torrey et Gray, Papilionaceae, exhibits various activities in a pathophysiological environment and has been widely employed to treat diseases. However, the effects of AS-IV on UA-induced pancreatic β-cell damage need to be investigated and the associating mechanism needs to be elucidated. This study was designed to determine the protective effects and underlying mechanism of AS-IV on UA-induced pancreatic β-cell dysfunction in T2D. Methods UA-treated Min6 cells were exposed to AS-IV or wortmannin. Thereafter, the 3-(45)-dimethylthiahiazo(-z-y1)-35-di-phenytetrazoliumromide (MTT) assay and flow cytometry were employed to determine the effect of AS-IV on cell proliferation and apoptosis, respectively. Insulin secretion was evaluated using the glucose-stimulated insulin secretion (GSIS) assay. Finally, western blot and quantitative real-time polymerase chain reaction (qRT-PCR) were performed to determine the effect of AS-IV on the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) pathway in UA-treated cells. Results AS-IV had no cytotoxic effects on Min6 cells. UA significantly suppressed Min6 cell growth, promoted cell apoptosis, and enhanced caspase-3 activity; however, AS-IV abolished these effects in a dose-dependent manner. Further, decreased insulin secretion was found in UA-treated Min6 cells compared to control cells, and the production of insulin was enhanced by AS-IV in a dose-dependent manner. AS-IV significantly increased phosphorylated (p)-AKT expression and the ratio of p-AKT/AKT in Min6 cells exposed to UA. No evident change in AKT mRNA level was found in the different groups. However, the effects of AS-IV on UA-stimulated Min6 cells were reversed by 100 nM wortmannin. Conclusion Collectively, our data suggest that AS-IV protected pancreatic β-cells from UA-treated dysfunction by activating the PI3K/AKT pathway. Such findings suggest that AS-IV may be an efficient natural agent against T2D.
Highlights
Diabetes mellitus (DM), a frequent chronic disease, is known to have a remarkable burden on public health [1]
Effects of Astragaloside IV (AS-IV) on Insulin Secretion in Glucose-Stimulated Min6 Cells. en, this study revealed the roles of AS-IV in Min6 cell dysfunction and adopted AS-IV (12.5, 25, and 50 μmol/l) and uric acid (UA) (5 mg/dl) to treat Min6 cells
DM is a familiar chronic disease that leads to cell injury, increases serum UA, and accelerates the progression of DM [22]
Summary
Diabetes mellitus (DM), a frequent chronic disease, is known to have a remarkable burden on public health [1]. Elevated uric acid (UA) has been found to damage pancreatic β-cell, promote oxidative stress, and cause insulin resistance in type 2 diabetes (T2D). The effects of AS-IV on UA-induced pancreatic β-cell damage need to be investigated and the associating mechanism needs to be elucidated. Is study was designed to determine the protective effects and underlying mechanism of AS-IV on UA-induced pancreatic β-cell dysfunction in T2D. UA significantly suppressed Min cell growth, promoted cell apoptosis, and enhanced caspase-3 activity; AS-IV abolished these effects in a dose-dependent manner. Our data suggest that AS-IV protected pancreatic β-cells from UAtreated dysfunction by activating the PI3K/AKT pathway. Such findings suggest that AS-IV may be an efficient natural agent against T2D
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