Horm Metab Res 2009; 41(11): 799-804
DOI: 10.1055/s-0029-1234043
Original Basic

© Georg Thieme Verlag KG Stuttgart · New York

Glucose, Metformin, and AICAR Regulate the Expression of G Protein-coupled Receptor Members in INS-1 β Cell

Q. R. Pan1 , W. H. Li1 , H. Wang1 , Q. Sun1 , X. H. Xiao1 , B. Brock2 , O. Schmitz2 , 3
  • 1Department of Endocrinology and Metabolism, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 1 Suaifuyuan Wangfujing Beijing, P. R. China
  • 2Institute of Pharmacology, University of Aarhus, Aarhus, Denmark
  • 3Department of Endocrinology and Diabetes, Aarhus University Hospital, Aarhus, Denmark
Further Information

Publication History

received 22.01.2009

accepted after second revision 30.06.2009

Publication Date:
11 August 2009 (eFirst)

Abstract

Glucagon-like peptide-1 receptor (GLP-1R), glucose-dependent insulinotropic polypeptide receptor (GIPR), and G protein-coupled receptor 40 (GPR40) are members of G protein-coupled receptors (GPCR) family. They are abundantly expressed in islet β cells, and mediate effects of incretins and fatty acids in β cells. Glucose and 5-AMP-activated protein kinase (AMPK) are known to be involved in the regulation of β cell function. Metformin and the potential therapeutic drug for type 2 diabetes, 5-amino-4-imidazolecarboxamide riboside (AICAR), are both known activators of AMPK. Here we studied the effects of glucose, metformin, and AICAR on the expression of GPCR in INS-1 β cell. INS-1 β cells were supplemented with different concentrations of glucose, metformin, or AICAR. The expressions of GLP-1R, GIPR, GPR40, and a nuclear transcription factor – peroxisome-proliferator activated receptor α (PPARα) – were analyzed by real-time RT-PCR and immunoblotting. The time-course of the mRNA degradation of these receptors was also monitored by applying actinomycin D to cells. We demonstrated that the expressions of GLP-1R, GIPR, and PPARα were downregulated when INS-1β cells were treated with glucose, while their expressions were upregulated when treated with metformin or AICAR. Glucose, metformin, or AICAR treatment had no obvious effect on the expression of GPR40. These results indicate that glucose, metformin, and AICAR regulated the expressions of incretin receptors and PPARα, but not GPR40 in β cells. Whether AMPK is a key regulator of these factors mediated receptor regulation remains to be investigated further.

References

Correspondence

Dr. W. H. Li

Department of Endocrinology and Metabolism

Peking Union Medical College Hospital

Chinese Academy of Medical Sciences and Peking Union Medical College

1 Suaifuyuan Wangfujing

100730 Beijing

P. R. China

Phone: +86/10/65 29 50 70

Fax: +86/10/65 29 40 70

Email: liwh@pumch.cn