Xiaoling Xu1, Shaoda Lin1, Yongsong Chen1, Xitao Li1, Shuhua Ma1, Yucai Fu2, Chiju Wei3, Chang Wang4, Wencan Xu5. 1. Department of Endocrinology, the First Affiliated Hospital of Shantou University Medical College, Shantou, China. 2. Laboratory of Cell Senescence, Shantou University Medical College, Shantou, China. 3. Multidisciplinary Research Center, Shantou University, Shantou, China. 4. Department of Neurology, Minsheng Hospital of Chaonan, Shantou, China. 5. Department of Endocrinology, the First Affiliated Hospital of Shantou University Medical College, Shantou, China xuwcan@163.com.
Abstract
OBJECTIVES: Type 2 Diabetes Mellitus (T2DM), which often accompanies dyslipidemia, is considered an inflammatory disease. GPR109A, as a niacin receptor, is up-regulated under high glucose concentration. Activation of GPR109A reduces GSIS and exerts anti-inflammatory effects by regulating NF-κB/IL-1β signaling. Metformin improves hyperglycemia, increases insulin sensitivity and attenuates the activation of the NF-κB pathway in T2DM. We aimed to examine whether metformin plays beneficial effects in T2DM by regulating the GPR109A signaling. METHODS: 117 T2DM patients were involved in this study and divided into two groups, the control group (without metformin) and the Metformin (Met) group (orally given metformin, 500mg-2000mg/d). Peripheral blood samples were collected from all the patients for testing PBL counts, biochemical data, and C peptide. Total RNA was isolated from PBLs. RT-PCR and immunocytochemistry were used to examine the expression of GPR109A, NF-κB and IL-1β in PBLs. RESULTS: FPG, HbA1c and LDL levels were lower and 2hr C peptide was higher in the Met group than in the control group (P<0.05). RT-PCR showed that mRNA levels of GPR109A, NF-κB and IL-1β were lower in the Met group than in the control group (P<0.05). Correlation analysis showed that there was a positive correlation between GPR109A and IL-1β (p<0.01, r=0.425) in the control group, GPR109A and IL-1β (p<0.05, r=0.256), GPR109A, and NF-κB (p<0.05,r=0.295) in the Met group. Immunocytochemistry showed that the GPR109A and NF-κB proteins were localized in the nucleus and cytoplasm of PBLs; however, there were no significant differences in the protein expression between the two groups. CONCLUSIONS: The results suggest that Met may reduce GPR109A expression in PBLs of T2DM patients by suppressing NF-κB/IL-1β signaling. Up-regulated expression of GPR109A may be an inflammatory consequence and the improvement of inflammation may down-regulate the expression of GPR109A in T2DM.
OBJECTIVES:Type 2 Diabetes Mellitus (T2DM), which often accompanies dyslipidemia, is considered an inflammatory disease. GPR109A, as a niacin receptor, is up-regulated under high glucose concentration. Activation of GPR109A reduces GSIS and exerts anti-inflammatory effects by regulating NF-κB/IL-1β signaling. Metformin improves hyperglycemia, increases insulin sensitivity and attenuates the activation of the NF-κB pathway in T2DM. We aimed to examine whether metformin plays beneficial effects in T2DM by regulating the GPR109A signaling. METHODS: 117 T2DM patients were involved in this study and divided into two groups, the control group (without metformin) and the Metformin (Met) group (orally given metformin, 500mg-2000mg/d). Peripheral blood samples were collected from all the patients for testing PBL counts, biochemical data, and C peptide. Total RNA was isolated from PBLs. RT-PCR and immunocytochemistry were used to examine the expression of GPR109A, NF-κB and IL-1β in PBLs. RESULTS: FPG, HbA1c and LDL levels were lower and 2hr C peptide was higher in the Met group than in the control group (P<0.05). RT-PCR showed that mRNA levels of GPR109A, NF-κB and IL-1β were lower in the Met group than in the control group (P<0.05). Correlation analysis showed that there was a positive correlation between GPR109A and IL-1β (p<0.01, r=0.425) in the control group, GPR109A and IL-1β (p<0.05, r=0.256), GPR109A, and NF-κB (p<0.05,r=0.295) in the Met group. Immunocytochemistry showed that the GPR109A and NF-κB proteins were localized in the nucleus and cytoplasm of PBLs; however, there were no significant differences in the protein expression between the two groups. CONCLUSIONS: The results suggest that Met may reduce GPR109A expression in PBLs of T2DM patients by suppressing NF-κB/IL-1β signaling. Up-regulated expression of GPR109A may be an inflammatory consequence and the improvement of inflammation may down-regulate the expression of GPR109A in T2DM.