Adhesion molecule CADM1 contributes to gap junctional communication among pancreatic islet α-cells and prevents their excessive secretion of glucagon
| Autor: | Yuki Ikeda, Takao Inoue, Naoki Ichiyanagi, Man Hagiyama, Akihiko Ito, Kazuyuki Hamaguchi, Minami A. Sakurai, Yoshinori Murakami, Keiko B. Kimura |
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| Rok vydání: | 2012 |
| Předmět: |
endocrine system
medicine.medical_specialty Cytoplasm Endocrinology Diabetes and Metabolism Immunoglobulins Cell Communication Biology Glucagon Connexins Islets of Langerhans Mice Endocrinology Cell–cell interaction Internal medicine medicine Cell Adhesion Animals Secretion RNA Small Interfering Cell adhesion Cells Cultured Mice Knockout geography geography.geographical_feature_category Cell adhesion molecule Pancreatic islets Cell Membrane Glucagon secretion Cell Adhesion Molecule-1 Gap Junctions Islet Cell biology medicine.anatomical_structure Glucagon-Secreting Cells Intercellular Signaling Peptides and Proteins Cell Adhesion Molecules |
| Zdroj: | Islets. 4(1) |
| ISSN: | 1938-2022 |
| Popis: | Cell adhesion molecule-1 (CADM1) is a recently identified adhesion molecule of pancreatic islet α-cells that mediates nerve-α-cell interactions via trans-homophilic binding and serves anatomical units for the autonomic control of glucagon secretion. CADM1 also mediates attachment between adjacent α-cells. Since gap junctional intercellular communication (GJIC) among islet cells is essential for islet hormone secretion, we examined whether CADM1 promotes GJIC among α-cells and subsequently participates in glucagon secretion regulation. Dye transfer assays using αTC6 mouse α-cells, which endogenously express CADM1, supported this possibility; efficient cell-to-cell spread of gap junction-permeable dye was detected in clusters of αTC6 cells transfected with nonspecific, but not with CADM1-targeting, siRNA. Immunocytochemical analysis of connexin 36, a major component of the gap junction among αTC6 cells, revealed that it was localized exclusively to the cell membrane in CADM1-non-targeted αTC6 cells, but diffusely to the cytoplasm in CADM1-targeted cells. Next, we incubated CADM1-targeted and non-targeted αTC6 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 α-cell attachment necessary for efficient GJIC. |
| Databáze: | OpenAIRE |
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