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| Content Provider | PubMed Central |
|---|---|
| Author | Tang, Guanghua Wang, Ying Park, Sangeun Bajpayee, Neil S. Diana, Vi Nagaoka, Yoshiko Lutz, Birnbaumer Jiang, Meisheng |
| Abstract | The neuropeptide galanin regulates numerous physiological activities in the body, including feeding and metabolism, learning and memory, nociception and spinal reflexes, and anxiety and related behaviors. Modulation of blood glucose levels by suppressing insulin release was the first reported activity for galanin. This inhibition was mediated by one or more pertussis toxin-sensitive G proteins of the Gi/o subfamily. However, the molecular identities of the specific G protein(s) and intracellular effectors have not been fully revealed. Recently, we demonstrated that mice lacking Go2, but not other members of the Gi/o protein family, secrete more insulin than controls upon glucose challenge, indicating that Go2 is a major transducer for the inhibitory regulation of insulin secretion. In this study, we investigated galanin signaling mechanisms in β cells using cell biological and electrophysiological approaches. We found that islets lacking Go2, but not other Gi/o proteins, lose the inhibitory effect of galanin on insulin release. Potentiation of ATP-sensitive potassium (KATP) and inhibition of calcium currents by galanin were disrupted by anti-Go2α antibodies. Galanin actions on KATP and calcium currents were completely lost in Go2−/− β cells. Furthermore, the hyperglycemic effect of galanin is also blunted in Go2−/− mice. Our results demonstrate that Go2 mediates the inhibition of insulin release by galanin by regulating both KATP and Ca2+ channels in mice. Our findings provide insight into galanin's action in glucose homeostasis. The results may also be relevant to the understanding of galanin signaling in other biological systems, especially the central nervous system. |
| Related Links | http://dx.doi.org/10.1073/pnas.1200100109 |
| Ending Page | 2641 |
| Page Count | 6 |
| Starting Page | 2636 |
| File Format | |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 7 |
| Volume Number | 109 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2012-02-14 |
| Access Restriction | Open |
| Rights Holder | National Academy of Sciences |
| Subject Keyword | General Research in Higher Education |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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