Combination of 20(R)-Rg3 and HUCMSCs Alleviates Type 2 Diabetes Mellitus in C57BL/6 Mice by Activating the PI3K/Akt...

Area of Science:

• Regenerative Medicine
• Endocrinology
• Pharmacology

Background:

• Type 2 diabetes mellitus (T2DM) presents a global health crisis, marked by insulin resistance and pancreatic beta-cell dysfunction.
• Human umbilical cord mesenchymal stem cells (HUCMSCs) show promise for T2DM treatment, but their effectiveness is limited by the in vivo environment.
• 20(R)-Rg3, a ginsenoside, possesses anti-inflammatory and antioxidant properties that may enhance HUCMSC function, yet the combined therapeutic strategy and its mechanisms require elucidation.

Purpose of the Study:

• To investigate the therapeutic effects of combining 20(R)-Rg3 with HUCMSCs in a mouse model of type 2 diabetes mellitus.
• To elucidate the underlying molecular mechanisms responsible for the synergistic effects of this combined cell-molecule therapy.
• To assess the impact on glycemic control, insulin resistance, metabolic parameters, and pancreatic islet function.

Main Methods:

• A high-fat diet and streptozotocin-induced T2DM mouse model was utilized.
• Mice were treated with phosphate-buffered saline (PBS), HUCMSCs alone, or HUCMSCs pre-treated with 20(R)-Rg3.
• Therapeutic efficacy was evaluated through blood glucose monitoring, glucose/insulin tolerance tests, serum biochemical analysis, histopathology, and RNA-sequencing (RNA-seq) of HUCMSCs.

Main Results:

• The combination therapy significantly reduced hyperglycemia and improved insulin sensitivity compared to HUCMSCs alone.
• Combined treatment ameliorated dyslipidemia, enhanced liver and kidney function, promoted glycogen synthesis, and facilitated pancreatic islet regeneration.
• Transcriptomic analysis revealed that the synergistic effect is primarily mediated by the activation of the PI3K/Akt signaling pathway.

Conclusions:

• 20(R)-Rg3 pretreatment potentiates the therapeutic efficacy of HUCMSCs in a T2DM mouse model.
• This combinatorial cell-molecule strategy demonstrates significant potential for improving metabolic dysfunction in type 2 diabetes.
• The PI3K/Akt pathway activation is identified as a key mechanism underlying the enhanced therapeutic benefits.