Puerarin protects pancreatic β-cell survival via PI3K/Akt signaling pathway

Abstract

Pancreatic b-cell loss because of apoptosis is the major cause of type 1 diabetes (T1D) and late stage T2D. Puerarin possesses anti-diabetic properties; whether it acts directly on pancreatic b-cell is not clear. This study was designed to investigate the effects of puerarin on pancreatic b-cell survival and function. Diabetes was induced in male C57BL/6 mice by a single peritoneal injection of streptozotocin (STZ). Pancreatic b-cell survival and function were assessed in diabetic mice by measuring b-cell apoptosis, b-cell mass, pancreatic insulin content, and glucose tolerance, and in cultured islets and clonial MIN6 b-cells by measuring b-cell viability and apoptosis and glucose-stimulated insulin secretion. We found that pre-treatment with puerarin decreased the incidence of STZ-induced diabetes. Puerarin increased pancreatic b-cell mass via b-cell apoptosis inhibition in diabetic mice, and increased serum insulin, whereas it decreased blood glucose levels and improved glucose tolerance. In cultured islets and MIN6 cells, puerarin protected b-cell from cobalt chloride (CoCl 2 )-induced apoptosis and restored the impaired capacity of glucose-stimulated insulin secretion. Puerarin protection of b-cell survival involved the phosphoinositide 3-kinase (PI3K) /Akt signaling pathway. In conclusion, puerarin protects pancreatic b-cell function and survival via direct effects on b-cells, and its protection of b-cell survival is mediated by the PI3K/Akt pathway. As a safe natural plant extraction, puerarin might serve as a preventive and/or therapeutic approach for diabetes.

Puerarin induces cell apoptosis in human chondrosarcoma cell line SW1353 via inhibition of the PI3K/Akt signaling pathway

“…A previous study demonstrated that puerarin protected pancreatic β-cell survival via the P13K/Akt signaling pathway (25). Neuroprotective effects of puerarin against beta-amyloid-induced neurotoxicity in PC12 cells were associated with activation of the PI3K-dependent signaling pathway (26).…”

Puerarin prevents tumor necrosis factor-α-induced apoptosis of PC12 cells via activation of the PI3K/Akt signaling pathway

“…A recent study indicated that puerarin restrained the progression of cardiac hypertrophy and apoptosis, which was probably mediated by the blockade of PI3K/Akt and JNK signaling pathways (23). In diabetic mice, puerarin exerted a protective effect on pancreatic β-cell function and survival, which was mediated via the PI3K/Akt pathway (24). Treatment with puerarin effectively inhibited lead-induced apoptosis in the kidney, which was associated with its antioxidant activity and its ability to modulate the PI3K/Akt/endothelial NO synthase signaling pathway (25).…”

The Neuroprotective Effect of Puerarin in Acute Spinal Cord Injury Rats

“…In SCI model, activation of the PI3K/Akt has also been demonstrated to mediate recovery of motor function [46]. Numerous bioactivities of puerarin were mediated through regulating the PI3K/Akt signaling pathway, including protection of pancreatic β-cell [47], prevention of osteoporosis [48], attenuation of hepatic fibrosis [49], alleviation of cardiac hypertrophy [50], as well as neuroprotection [51][52][53]. Interestingly, the majority of studies demonstrated that puerarin exerted bioactivities via activating the PI3K/Akt pathway, whereas some of the studies reported that the therapeutic effects of puerarin were mediated via blocking PI3K/Akt [49,50].…”