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. 2022 Feb;13(2):2217-2225.
doi: 10.1080/21655979.2021.2023996.

Diosgenin reduces phosphodiesterase 3B (PDE3B) through AMP-activated protein kinase/ mechanistic target of rapamycin (AMPK/mTOR) signaling pathway to ameliorate streptozotocin-induced pancreatic β-cell apoptosis and dysfunction

Lijie Ma  1   2 , Chengfei Zhang  3 , Lili Wu  4 , Lingling Qin  5 , Tonghua Liu  4
Affiliations

Diosgenin reduces phosphodiesterase 3B (PDE3B) through AMP-activated protein kinase/ mechanistic target of rapamycin (AMPK/mTOR) signaling pathway to ameliorate streptozotocin-induced pancreatic β-cell apoptosis and dysfunction

Lijie Ma et al. Bioengineered. 2022 Feb.

Abstract

Diabetes mellitus is a metabolic disease caused by defective insulin secretion and/or insulin action. And insulin is the main hormone released by the pancreatic β-cells. Diosgenin (DG) is a phytochemical with pharmacological activity that increases insulin secretion in streptozotocin (STZ)-induced pancreatic β-cells of diabetic rats. In this paper, we investigated the effect and mechanism of DG on cell apoptosis and dysfunction in STZ-induced pancreatic β-cells. Cell viability was detected by CCK-8, apoptosis by flow cytometry, and apoptosis-related protein expression by Western blot. Western blot and RT-qPCR were performed to detect the expression of related genes. The results showed that in STZ-induced INS-1 cells, DG could improve cell viability, inhibit apoptosis, attenuate oxidative stress levels and increase insulin secretion. Notably, PDE3B was highly expressed in STZ-induced INS-1 cells, while DG could significantly inhibit PDE3B expression in a dose-dependent manner. More importantly, overexpression PDE3B remarkably reversed the effect of DG on STZ-induced INS-1 cells. It is thus clear that DG might inhibit STZ-treated pancreatic β-cell apoptosis and reduce dysfunction via downregulating PDE3B, which provided a more reliable theoretical basis for the treatment of diabetes mellitus with DG.

Keywords: Type 2 diabetes mellitus (T2DM); diosgenin; phosphodiesterase 3B (PDE3B); streptozotocin (STZ).

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Conflict of interest statement

No potential conflict of interest was reported by the author(s).

Figures

Figure 1.
Figure 1.
DG increases cell viability and inhibits apoptosis in STZ-induced INS-1 cells. (a) Results of cell viability with different concentrations of DG in INS-1 cells. (b) Results of cell viability with different concentrations of DG in STZ-induced INS-1 cells. (c) Results of LDH activity. (d) Apoptosis detection by flow cytometry. (e) Results of apoptosis-related protein expression, inculding Bcl-2, Bax, and cleaved caspase3/caspase3. ***P < 0.001 vs. control; #P < 0.05, ####P < 0.01 and ###P < 0.001 vs. STZ.
Figure 2.
Figure 2.
DG improves insulin secretion and reduces oxidative stress levels in STZ-induced INS-1 cells. (a) Results of insulin secretion levels. (b) Results of insulin gene level detection by RT-qPCR. (c) Results of oxidative stress indicators, including MDA, SOD and GSH-Px. ***P < 0.001 vs. control; #P < 0.05, ##P < 0.01 and ###P < 0.001 vs. STZ.
Figure 3.
Figure 3.
DG inhibits PDE3B expression and affects AMPK/mTOR signaling pathway. (a) The PDE3B mRNA expression in STZ-induced INS-1 cells. (b) The PDE3B protein expression in STZ-induced INS-1 cells. (c) The related-protein expression of AMPK/mTOR pathway. ***P < 0.001 vs. control; ##P < 0.01 and ###P < 0.001 vs. STZ.
Figure 4.
Figure 4.
DG increases cell viability and inhibits apoptosis in STZ-induced INS-1 cells via inhibiting PDE3B. (a) The mRNA expression of PDE3B in INS-1 cells. (b) The protein expression of PDE3B in INS-1 cells. (c) Results of cell viability. (d) Results of LDH activity. (e) Apoptosis detection by flow cytometry. (f) Results of apoptosis-related protein expression, inculding Bcl-2, Bax, and cleaved caspase3/caspase3. ***P < 0.001 vs. Ov-NC or control. ###P < 0.001 vs. STZ. ΔP<0.05, ΔΔP<0.01 and ΔΔΔP<0.001 vs. STZ+DG+Ov-NC.
Figure 5.
Figure 5.
DG improves insulin secretion and reduces oxidative stress levels in STZ-induced INS-1 cells via inhibiting PDE3B. (a) Results of insulin secretion levels. (b) Results of insulin gene level detection by RT-qPCR. (c) Results of oxidative stress indicators, including MDA, SOD and GSH-Px. ***P < 0.001 vs. Ov-NC or control. ###P < 0.001 vs. STZ. ΔP<0.05, ΔΔP<0.01 and ΔΔΔP<0.001 vs. STZ+DG+Ov-NC.
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Key Laboratory of Traditional Chinese Medicine Health Cultivation of Beijing [NO. BZ0259], Innovation and Intelligence Base of Traditional Chinese Medicine for Prevention and Treatment of Diabetes and its Complications [NO. B20055].

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