The Effect of Metformin on the Expression of GPR109A, NF-κB and IL-1β in Peripheral Blood Leukocytes from Patients with Type 2 Diabetes Mellitus

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.