Zhi-Shen Pill ameliorates impaired glucose tolerance by targeting pancreatic β-cell and adipocyte pathways

Zhi-Shen Pill (ZSP), a traditional Chinese medicine formula with a history of use in regulating glucose metabolism, was chosen as potential IGT treatment due to its ethnopharmacological relevance.

To investigate and elucidate the underlying mechanism of Zhi-Shen Pill (ZSP) in IGT treatment through regulating the function of pancreatic β cells-adipocytes.

3-Deoxyglucosone(3-DG) was employed to establish IGT cell models in INS-1 cells and 3T3 L1 cells. Cell viability, apoptosis, insulin secretion, and key proteins associated with STRs axis, Adiponectin (APN)-adipoR1 axis, and insulin signaling were assessed using Cell Counting Kit-8 (CCK-8), flow cytometry (FCM), Western blot and cell immunofluorescence imaging. The downstream signals of STRs such as cyclic adenosine monophosphate (cAMP) and Ca²⁺ were quantified through fluorescence report proteins and live-cell Ca²⁺ imaging, respectively.

Under IGT conditions, ZSP intervention exhibited potential anti-IGT activity. It promoted insulin production and release in INS-1 cells (with double changes in the high-dose group), improved insulin sensitivity in 3T3 L1 cells, and increased the levels of Sirtuin family including sirtuin1 (SIRT1) (p < 0.001, n = 3, in high-dose group) and SIRT6 (p < 0.001, n = 3, in high-dose group) in 3T3 L1 cells. In addition, ZSP mediates its functional activities by interacting synergistically with AMP-activated protein kinase (AMPK), thereby inhibiting the transcriptional activation of key inflammatory factors.

These findings suggest that ZSP may serve as a potential therapeutic formula in traditional Chinese medicine (TCM) for IGT treatment.