C Y Liu1, Y N Hao1, F Yin2, Y L Zhang1, J H Liu3. 1. Chongqing Key Lab of Medicinal Chemistry & Molecular Pharmacology, Chongqing University of Technology, Chongqing, 400054, China. 2. Chongqing Key Lab of Medicinal Chemistry & Molecular Pharmacology, Chongqing University of Technology, Chongqing, 400054, China. fyin@cqut.edu.cn. 3. Chongqing Key Lab of Medicinal Chemistry & Molecular Pharmacology, Chongqing University of Technology, Chongqing, 400054, China. jhliu@cqut.edu.cn.
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.
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.
Entities:
Keywords:
Geniposide; Glucose-stimulated insulin secretion (GSIS); Proteasome degradation; Thioredoxin-interacting protein (Txnip); Type 2 diabetes mellitus (T2DM)
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