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Niacin receptor GPR109A inhibits insulin secretion and is down-regulated in type 2 diabetic islet beta-cells.
Gen Comp Endocrinol. 2016 Oct 01; 237:98-108.GC

Abstract

OBJECTIVES

We previously found niacin receptor GPR109A was expressed in murine islet beta-cells, and signaling through GPR109A inhibited glucose stimulated insulin secretion (GSIS). However, the expression of GPR109A in human islets and its functional relevance is still not known.

METHODS

The expression of GPR109A was examined by antibody staining and in situ hybridization on pancreatic paraffin sections. GPR109A was cloned and expressed in INS-1 islet beta-cells. Intracellular cAMP and GSIS were determined using enzyme-linked immunosorbent assay (ELISA).

RESULTS

The expression of GPR109A was confirmed in murine islet beta-cells and further detected in human counterparts by using commercially available polyclonal antibodies. In situ hybridization study detected the transcripts of GPR109A, but not that of closely related GPR109B. Furthermore, GPR109A was significantly reduced in islets from diabetic individuals and animal model of db/db mice as compared to their respective controls. Further, GPR109A levels in insulinoma were also reduced dramatically as compared to islets found in corresponding non-tumor normal tissues. Quantitative RT-PCR analysis demonstrated that GPR109A transcripts were severely down-regulated in rodent insulinoma cell lines as compared to that of freshly isolated islets from mice. Finally, human and murine GPR109A expression cassettes were transfected into INS-1 cells, which resulted in reduced accumulation of cAMP and insulin secretion after incubation with niacin. The effect could be completely abrogated by pretreatment with pertussis toxin.

CONCLUSIONS

These results demonstrate that GPR109A is functionally expressed in both human and murine islet beta-cells. However, the role of GPR109A in the prevention of diabetes or insulinoma needs further study.

Authors+Show Affiliations

Multidisciplinary Research Center, Shantou University, Shantou 515063, Guangdong, China.Department of Pathology, Xinan Hospital of Chongqing, Chongqing 400038, China.Multidisciplinary Research Center, Shantou University, Shantou 515063, Guangdong, China.Multidisciplinary Research Center, Shantou University, Shantou 515063, Guangdong, China.Multidisciplinary Research Center, Shantou University, Shantou 515063, Guangdong, China.Multidisciplinary Research Center, Shantou University, Shantou 515063, Guangdong, China.Laboratory of Cell Senescence, Shantou University Medical College, Shantou, Guangdong 515041, China.Department of Endocrinology, The First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong 515041, China. Electronic address: xuwcan@163.com.Multidisciplinary Research Center, Shantou University, Shantou 515063, Guangdong, China. Electronic address: chijuwei@stu.edu.cn.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

27570060

Citation

Wang, Na, et al. "Niacin Receptor GPR109A Inhibits Insulin Secretion and Is Down-regulated in Type 2 Diabetic Islet Beta-cells." General and Comparative Endocrinology, vol. 237, 2016, pp. 98-108.
Wang N, Guo DY, Tian X, et al. Niacin receptor GPR109A inhibits insulin secretion and is down-regulated in type 2 diabetic islet beta-cells. Gen Comp Endocrinol. 2016;237:98-108.
Wang, N., Guo, D. Y., Tian, X., Lin, H. P., Li, Y. P., Chen, S. J., Fu, Y. C., Xu, W. C., & Wei, C. J. (2016). Niacin receptor GPR109A inhibits insulin secretion and is down-regulated in type 2 diabetic islet beta-cells. General and Comparative Endocrinology, 237, 98-108. https://doi.org/10.1016/j.ygcen.2016.08.011
Wang N, et al. Niacin Receptor GPR109A Inhibits Insulin Secretion and Is Down-regulated in Type 2 Diabetic Islet Beta-cells. Gen Comp Endocrinol. 2016 Oct 1;237:98-108. PubMed PMID: 27570060.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Niacin receptor GPR109A inhibits insulin secretion and is down-regulated in type 2 diabetic islet beta-cells. AU - Wang,Na, AU - Guo,De-Yu, AU - Tian,Xiong, AU - Lin,Hao-Peng, AU - Li,Yun-Pan, AU - Chen,Shao-Jun, AU - Fu,Yu-Cai, AU - Xu,Wen-Can, AU - Wei,Chi-Ju, Y1 - 2016/08/26/ PY - 2016/03/22/received PY - 2016/07/18/revised PY - 2016/08/24/accepted PY - 2016/8/30/pubmed PY - 2017/9/5/medline PY - 2016/8/30/entrez KW - Diabetes KW - GPR109A KW - Insulin secretion KW - Insulinoma KW - Niacin SP - 98 EP - 108 JF - General and comparative endocrinology JO - Gen Comp Endocrinol VL - 237 N2 - OBJECTIVES: We previously found niacin receptor GPR109A was expressed in murine islet beta-cells, and signaling through GPR109A inhibited glucose stimulated insulin secretion (GSIS). However, the expression of GPR109A in human islets and its functional relevance is still not known. METHODS: The expression of GPR109A was examined by antibody staining and in situ hybridization on pancreatic paraffin sections. GPR109A was cloned and expressed in INS-1 islet beta-cells. Intracellular cAMP and GSIS were determined using enzyme-linked immunosorbent assay (ELISA). RESULTS: The expression of GPR109A was confirmed in murine islet beta-cells and further detected in human counterparts by using commercially available polyclonal antibodies. In situ hybridization study detected the transcripts of GPR109A, but not that of closely related GPR109B. Furthermore, GPR109A was significantly reduced in islets from diabetic individuals and animal model of db/db mice as compared to their respective controls. Further, GPR109A levels in insulinoma were also reduced dramatically as compared to islets found in corresponding non-tumor normal tissues. Quantitative RT-PCR analysis demonstrated that GPR109A transcripts were severely down-regulated in rodent insulinoma cell lines as compared to that of freshly isolated islets from mice. Finally, human and murine GPR109A expression cassettes were transfected into INS-1 cells, which resulted in reduced accumulation of cAMP and insulin secretion after incubation with niacin. The effect could be completely abrogated by pretreatment with pertussis toxin. CONCLUSIONS: These results demonstrate that GPR109A is functionally expressed in both human and murine islet beta-cells. However, the role of GPR109A in the prevention of diabetes or insulinoma needs further study. SN - 1095-6840 UR - https://www.unboundmedicine.com/medline/citation/27570060/Niacin_receptor_GPR109A_inhibits_insulin_secretion_and_is_down_regulated_in_type_2_diabetic_islet_beta_cells_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0016-6480(16)30250-7 DB - PRIME DP - Unbound Medicine ER -