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| Content Provider | Journal of Biological Chemistry (JBC) |
|---|---|
| Author | Shiota, Chiyo Larsson, Olof Shelton, Kathy D. Shiota, Masakazu Efanov, Alexander M. Høy, Marianne Lindner, Jill Kooptiwut, Suwattanee Juntti-Berggren, Lisa Gromada, Jesper Berggren, Per-Olof Magnuson, Mark A. |
| Abstract | The ATP-sensitive potassium channel is a key molecular complex for glucose-stimulated insulin secretion in pancreatic β cells. In humans, mutations in either of the two subunits for this channel, the sulfonylurea type 1 receptor (Sur1) or Kir6.2, cause persistent hyperinsulinemic hypoglycemia of infancy. We have generated and characterized Sur1 null mice. Interestingly, these animals remain euglycemic for a large portion of their life despite constant depolarization of membrane, elevated cytoplasmic free Ca2+ concentrations, and intact sensitivity of the exocytotic machinery to Ca2+. A comparison of glucose- and meal-stimulated insulin secretion showed that, although Sur1 null mice do not secrete insulin in response to glucose, they secrete nearly normal amounts of insulin in response to feeding. Because Sur1 null mice lack an insulin secretory response to GLP-1, even though their islets exhibit a normal rise in cAMP by GLP-1, we tested their response to cholinergic stimulation. We found that perfused Sur1 null pancreata secreted insulin in response to the cholinergic agonist carbachol in a glucose-dependent manner. Together, these findings suggest that cholinergic stimulation is one of the mechanisms that compensate for the severely impaired response to glucose and GLP-1 brought on by the absence of Sur1, thereby allowing euglycemia to be maintained. |
| Related Links | http://www.jbc.org/content/277/40/37176.abstract |
| Ending Page | 37183 |
| Starting Page | 37176 |
| Page Count | 8 |
| File Format | HTM / HTML PDF |
| ISSN | 00219258 |
| Journal | Journal of Biological Chemistry (JBC) |
| Issue Number | 40 |
| Volume Number | 277 |
| DOI | 10.1074/jbc.M206757200 |
| e-ISSN | 1083351X |
| Language | English |
| Publisher | American Society for Biochemistry and Molecular Biology |
| Publisher Date | 2002-10-04 |
| Access Restriction | Open |
| Subject Keyword | ATP-sensitive potassium channel (KATPchannel) Cytoplasmic free Ca2+ concentration ([Ca2+]i) Sulfonylurea receptor type 1 (Sur1) Persistent hyperinsulinemic hypoglycemia of infancy (PHHI) Radioimmunoassay (RIA) Enzyme-linked immunosorbent assay (ELISA) Glucagon-like peptide 1 (GLP-1) Kilobase pair(s) (kbp) Protein kinase A (PKA) METABOLISM AND BIOENERGETICS |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Biochemistry Molecular Biology |
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