| First Author | Ito A | Year | 2012 |
| Journal | Islets | Volume | 4 |
| Issue | 1 | Pages | 49-55 |
| PubMed ID | 22513384 | Mgi Jnum | J:317598 |
| Mgi Id | MGI:6855008 | Doi | 10.4161/isl.18675 |
| Citation | Ito A, et al. (2012) Adhesion molecule CADM1 contributes to gap junctional communication among pancreatic islet alpha-cells and prevents their excessive secretion of glucagon. Islets 4(1):49-55 |
| abstractText | Cell adhesion molecule-1 (CADM1) is a recently identified adhesion molecule of pancreatic islet alpha-cells that mediates nerve-alpha-cell interactions via trans-homophilic binding and serves anatomical units for the autonomic control of glucagon secretion. CADM1 also mediates attachment between adjacent alpha-cells. Since gap junctional intercellular communication (GJIC) among islet cells is essential for islet hormone secretion, we examined whether CADM1 promotes GJIC among alpha-cells and subsequently participates in glucagon secretion regulation. Dye transfer assays using alphaTC6 mouse alpha-cells, which endogenously express CADM1, supported this possibility; efficient cell-to-cell spread of gap junction-permeable dye was detected in clusters of alphaTC6 cells transfected with nonspecific, but not with CADM1-targeting, siRNA. Immunocytochemical analysis of connexin 36, a major component of the gap junction among alphaTC6 cells, revealed that it was localized exclusively to the cell membrane in CADM1-non-targeted alphaTC6 cells, but diffusely to the cytoplasm in CADM1-targeted cells. Next, we incubated CADM1-targeted and non-targeted alphaTC6 cells in a medium containing 1 mM glucose and 200 mM arginine for 30 min to induce glucagon secretion, and found that the targeted cells secreted three times more glucagon than did the non-targeted. We conducted similar experiments using pancreatic islets that were freshly isolated from wild-type and CADM1-knockout mice, and expressed glucagon secretion as ratios relative to baseline values. The increase in ratio was larger in CADM1-knockout islets than in wild-type islets. These results suggest that CADM1 may serve as a volume limiter of glucagon secretion by sustaining alpha-cell attachment necessary for efficient GJIC. |
