Geniposide accelerates proteasome degradation of Txnip to inhibit insulin secretion in pancreatic β-cells

Abstract

Purpose

To analyze the role of geniposide in the protein degradation of Txnip and to determine the impact of Txnip on geniposide-regulated GSIS in pancreatic INS-1 cells.

Methods

The content of Txnip protein was measured by western blot; insulin content and glucose uptake were determined by ELISA; and knockdown of Txnip was the method of RNA interference.

Results

Glucose induces a rapid increase in Txnip protein, and geniposide accelerates the degradation of Txnip via proteasome pathway in the presence of high glucose (25 mM) in INS-1 pancreatic β-cells. And MG132, a proteasomal inhibitor, potentiates glucose uptake, metabolism (ATP production) and glucose-stimulated insulin secretion (GSIS) in high-glucose (25 mM)-treated INS-1 cells, but geniposide significantly prevents these effects. Furthermore, the combination of geniposide and Txnip knockdown shows substantial synergistic effects to reduce glucose uptake, metabolism and GSIS in high-glucose (25 mM)-treated INS-1 cells.

Conclusions

Txnip protein played an essential role in glucose uptake, metabolism and GSIS, and geniposide could accelerate the degradation via proteasome pathway in high-glucose-treated pancreatic INS-1 cells.

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