Xue Yang1, Yuqing Zhang1, Wan Xu1, Ruyuan Deng1, Yun Liu1, Fengying Li1, Yao Wang1, Xueying Ji1, Mengyao Bai1, Feiye Zhou1, Libin Zhou2, Xiao Wang3. 1. Shanghai Clinical Center for Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Department of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, 197 Ruijin Road II, Shanghai, 200025, China. 2. Shanghai Clinical Center for Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Department of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, 197 Ruijin Road II, Shanghai, 200025, China. libinzhou99@hotmail.com. 3. Shanghai Clinical Center for Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Department of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, 197 Ruijin Road II, Shanghai, 200025, China. wangxiao1976@hotmail.com.
Abstract
AIMS: The preservation of pancreatic β-cell function is a key point in the treatment of type 2 diabetes mellitus. There is substantial evidence demonstrating that heat-shock protein 90 (Hsp90) is needed for the stabilization and correct folding of client proteins and plays important roles in various biological processes. Here, we revealed the important role of Hsp90 in β-cell function. METHODS: Islets from male Sprague-Dawley rats were isolated to be used for further RT-PCR, Western blot, and insulin secretion test ex vivo in response to different stimuli. RESULTS: Our results revealed that Hsp90 expression was significantly decreased in isolated rat islets exposed to high glucose, which was involved in glucokinase activation and glucose metabolism, not calcium signaling. Two kinds of Hsp90 inhibitors 17-DMAG and CCT018159 markedly enhanced glucose-stimulated insulin secretion from rat islets, along with increased expressions of genes closely related to β-cell function. CONCLUSIONS: These data indicate that Hsp90 may be involved in high glucose-induced islet function adaptation.
AIMS: The preservation of pancreatic β-cell function is a key point in the treatment of type 2 diabetes mellitus. There is substantial evidence demonstrating that heat-shock protein 90 (Hsp90) is needed for the stabilization and correct folding of client proteins and plays important roles in various biological processes. Here, we revealed the important role of Hsp90 in β-cell function. METHODS: Islets from male Sprague-Dawley rats were isolated to be used for further RT-PCR, Western blot, and insulin secretion test ex vivo in response to different stimuli. RESULTS: Our results revealed that Hsp90 expression was significantly decreased in isolated rat islets exposed to high glucose, which was involved in glucokinase activation and glucose metabolism, not calcium signaling. Two kinds of Hsp90 inhibitors 17-DMAG and CCT018159 markedly enhanced glucose-stimulated insulin secretion from rat islets, along with increased expressions of genes closely related to β-cell function. CONCLUSIONS: These data indicate that Hsp90 may be involved in high glucose-induced islet function adaptation.
Entities:
Keywords:
Glucose; Hsp90; Insulin secretion; Type 2 diabetes mellitus