Saponins of Momordica charantia increase insulin secretion in INS-1 pancreatic ß-cells via the PI3K/Akt/FoxO1 signaling pathway.

Saponins are the main bioactive substances with anti-hyperglycemic activities of Momordica charantia. This study aimed to verify the effects of M. charantia saponins on insulin secretion and explore the potential underlying mechanisms in INS-1 pancreatic ß-cells. We injured INS-1 cells with 33.3mM glucose and then treated them with saponins. Saponins improved cell morphology and viability as demonstrated by inverted microscopy and CCK8 detection and significantly increased insulin secretion in a concentration-dependent manner as shown by ELISA. Thus, we obtained the optimal concentration for the subsequent experiments. Potential mechanisms were explored by immunofluorescence, western blotting, and RT-qPCR techniques. First, saponins increased the mRNA and protein levels of IRS-2 but decreased the serine 731 phosphorylation level of IRS-2. Moreover, saponins increased the phosphorylation of Akt protein and decreased the protein level of FoxO1, which were both reversed by the PI3K inhibitor ly294002. Furthermore, saponins increased the protein level of the downstream molecule and insulin initiating factor PDX-1, which was also reversed by ly294002. Saponins also increased Akt and PDX-1 mRNA and decreased FoxO1 mRNA, which were both reversed by ly294002. Saponins increased glucose-stimulated insulin secretion (GSIS) and intracellular insulin content, which were reversed by ly294002, as determined by ELISA. The immunofluorescence results also confirmed this tendency. In conclusion, our findings improve our understanding of the function of saponins in INS-1 pancreatic ß-cells and suggest that saponins may increase insulin secretion via the PI3K/Akt/FoxO1 signaling pathway.

Correlation Between Thioredoxin-Interacting Protein and Nerve Conduction Velocity in Patients With Type 2 Diabetes Mellitus.

Aims: To investigate the correlation between thioredoxin-interacting protein (TXNIP) and peripheral nerve conduction velocity (NCV) in patients with type 2 diabetes mellitus. Methods: In total, 338 patients with type 2 diabetes mellitus (T2DM) were included in this study. We collected the clinical data and measured the motor conduction velocities of the bilateral ulnar nerve, median nerve, tibial nerve, and common peroneal nerve, and the sensory conduction velocities of the ulnar nerve, median nerve, sural nerve, and superficial peroneal nerve. According to the results, the patients were divided into two groups: normal peripheral nerve conduction group (NCVN group) and abnormal peripheral nerve conduction group (NCVA group). The two groups were then compared in terms of the conventional biochemical index and the sugar metabolic index as well as the serum levels of TXNIP, reduced glutathione (GSH), total superoxide dismutase (SOD), malondialdehyde (MDA), and tumor necrosis factor alpha (TNF-α). The correlation between TXNIP and NCV was also analyzed. Results: Compared with the NCVN group, the TXNIP and MDA values were significantly increased in the NCVA group (P < 0.05). Among the patients with T2DM, age, fasting glucose, SDBG, and TXNIP were risk factors for NCV abnormality, while vitamin D3 was a protective factor. After adjusting for related confounding factors, TXNIP was significantly correlated with NCV (P < 0.05). Among the patients with T2DM, TXNIP was an independent risk factor for left ulnar motor conduction velocity (MCV), right ulnar MCV, left median MCV, and right median MCV. TNF-α was identified as a positive influencing factor for serum TXNIP, while serum TXNIP was a positive factor for TNF-α and MDA (both P < 0.05). Conclusion: Serum TXNIP is related to NCV in T2DM patients. In combination with oxidative stress and inflammation, TXNIP may affect diabetic peripheral neuropathy (DPN).

Diosgenin induces apoptosis in IGF-1-stimulated human thyrocytes through two caspase-dependent pathways.

Insulin-like growth factor-1 (IGF-1) is a growth factor of the thyroid that has been shown in our previous study to possess proliferative and antiapoptotic effects in FRTL-5 cell lines through the upregulation of cyclin D and Fas-associated death domain-like interleukin-1-converting enzyme (FLICE)-inhibitory protein (FLIP). Diosgenin, a natural steroid sapogenin from plants, has been shown to induce apoptosis in many cell lines, with the exception of thyroid cells. In this report, we investigated the apoptotic effect and mechanism of diosgenin in IGF-1-stimulated primary human thyrocytes. Primary human thyrocytes were preincubated with or without IGF-1 for 24h and subsequently exposed to varying concentrations of diosgenin for different times. We found that diosgenin induced apoptosis in human thyrocytes pretreated with IGF-1 in a dose-dependent manner through the activation of caspase cascades. Moreover, diosgenin inhibited FLIP and activated caspase-8 in the FAS-related apoptotic pathway. Diosgenin increased the production of ROS, regulated the balance of Bax and Bcl-2 and cleaved caspase-9 in the mitochondrial apoptotic pathway. These results indicate that diosgenin induces apoptosis in IGF-1-stimulated primary human thyrocytes through two caspase-dependent pathways.