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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.
Ann Clin Lab Sci. 2017 Sep; 47(5):556-562.AC

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.

Authors+Show Affiliations

Department of Endocrinology, the First Affiliated Hospital of Shantou University Medical College, Shantou, China.Department of Endocrinology, the First Affiliated Hospital of Shantou University Medical College, Shantou, China.Department of Endocrinology, the First Affiliated Hospital of Shantou University Medical College, Shantou, China.Department of Endocrinology, the First Affiliated Hospital of Shantou University Medical College, Shantou, China.Department of Endocrinology, the First Affiliated Hospital of Shantou University Medical College, Shantou, China.Laboratory of Cell Senescence, Shantou University Medical College, Shantou, China.Multidisciplinary Research Center, Shantou University, Shantou, China.Department of Neurology, Minsheng Hospital of Chaonan, Shantou, China.Department of Endocrinology, the First Affiliated Hospital of Shantou University Medical College, Shantou, China xuwcan@163.com.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

29066482

Citation

Xu, Xiaoling, et al. "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." Annals of Clinical and Laboratory Science, vol. 47, no. 5, 2017, pp. 556-562.
Xu X, Lin S, Chen Y, et al. 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. Ann Clin Lab Sci. 2017;47(5):556-562.
Xu, X., Lin, S., Chen, Y., Li, X., Ma, S., Fu, Y., Wei, C., Wang, C., & Xu, W. (2017). 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. Annals of Clinical and Laboratory Science, 47(5), 556-562.
Xu X, et al. 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. Ann Clin Lab Sci. 2017;47(5):556-562. PubMed PMID: 29066482.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Xu,Xiaoling, AU - Lin,Shaoda, AU - Chen,Yongsong, AU - Li,Xitao, AU - Ma,Shuhua, AU - Fu,Yucai, AU - Wei,Chiju, AU - Wang,Chang, AU - Xu,Wencan, PY - 2017/10/26/entrez PY - 2017/10/27/pubmed PY - 2018/1/27/medline SP - 556 EP - 562 JF - Annals of clinical and laboratory science JO - Ann Clin Lab Sci VL - 47 IS - 5 N2 - 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. SN - 1550-8080 UR - https://www.unboundmedicine.com/medline/citation/29066482/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_ L2 - http://www.annclinlabsci.org/cgi/pmidlookup?view=long&amp;pmid=29066482 DB - PRIME DP - Unbound Medicine ER -