title: Nicotinic acid inhibits glucose-stimulated insulin secretion via the G protein-coupled receptor PUMA-G in murine islet β cells.
abstract: OBJECTIVE
  Chronic administration of nicotinic acid (NA), a potent antilipidemic compound, aggravates glycemic control in diabetic patients. It is not known if NA has direct effects on islet β cells.
  
  
  METHODS
  Real-time reverse transcriptase-polymerase chain reaction, in situ hybridization, and immunofluorescence techniques were used to examine the expression of NA receptor PUMA-G, a member of the G protein-coupled receptor (G-PCR) family, in murine islet β cells. Calcium transient was measured using confocal microscopy, whereas the intracellular cyclic adenosine monophosphate and glucose-stimulated insulin secretion (GSIS) from isolated islets were determined by the enzyme-linked immunosorbent assay.
  
  
  RESULTS
  High levels of PUMA-G transcripts and protein were detected in all β cells, and about 40% of α cells. PUMA-G transcripts increased more than 3-fold in islets incubated with interferon γ. Cyclic adenosine monophosphate accumulation, induced by IBMX/forskolin, was inhibited by NA; however, the inhibition was completely abolished by pretreatment of the culture with pertussis toxin. No calcium transient was detected in islet cells in the presence of NA. Static incubation of islets with NA led to an approximately 30% reduction of GSIS.
  
  
  CONCLUSIONS
  The results indicated that PUMA-G stimulation by NA in islet β cells inhibited GSIS likely via activation of the Gi signaling pathway.
authors: Multidisciplinary Research Center, Shantou University, Shantou, Guangdong, China.
authors: Hong-ming
authors: HM
authors: Li
authors: Mei
authors: M
authors: Zhang
authors: Sheng-tao
authors: ST
authors: Xu
authors: Di-zheng
authors: DZ
authors: Li
authors: Lin-yun
authors: LY
authors: Zhu
authors: Si-wu
authors: SW
authors: Peng
authors: Guo-qiang
authors: GQ
authors: Chen
authors: Pamela M
authors: PM
authors: Martin
authors: Vadivel
authors: V
authors: Ganapathy
authors: Chi-ju
authors: CJ
authors: Wei
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D005947:Glucose / Q000494:pharmacology*; D017403:In Situ Hybridization; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000378:metabolism; D007371:Interferon-gamma / Q000494:pharmacology; D007515:Islets of Langerhans / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D018613:Microscopy, Confocal; D009525:Niacin / Q000494:pharmacology*; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism*; D011978:Receptors, Nicotinic / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014665:Vasodilator Agents
chemical_list: C473652:Hcar2 protein, mouse; D007328:Insulin; D043562:Receptors, G-Protein-Coupled; D011978:Receptors, Nicotinic; D014665:Vasodilator Agents; D009525:Niacin; D007371:Interferon-gamma; D000242:Cyclic AMP; D005947:Glucose; D002118:Calcium