| First Author | Somvanshi RK | Year | 2018 |
| Journal | Biochim Biophys Acta | Volume | 1864 |
| Issue | 2 | Pages | 359-373 |
| PubMed ID | 29104117 | Mgi Jnum | J:257538 |
| Mgi Id | MGI:6119336 | Doi | 10.1016/j.bbadis.2017.11.002 |
| Citation | Somvanshi RK, et al. (2018) Characterization of somatostatin receptors and associated signaling pathways in pancreas of R6/2 transgenic mice. Biochim Biophys Acta 1864(2):359-373 |
| abstractText | The present study describes the status of somatostatin receptors (SSTRs) and their colocalization with insulin (beta), glucagon (alpha) and somatostatin (delta) producing cells in the pancreatic islets of 11weeks old R6/2 Huntington''s Disease transgenic (HD tg) and age-matched wild type (wt) mice. We also determined expression of tyrosine hydroxylase (TH), glutamic acid decarboxylase (GAD) and presynaptic marker synaptophysin (SYP) in addition to signal transduction pathways associated with diabetes. In R6/2 mice, islets are relatively smaller in size, exhibit enhanced expression and nuclear inclusion of mHtt along with the loss of insulin, glucagon and somatostatin expression. In comparison to wt, R6/2 mice display enhanced mRNA for all SSTRs except SSTR2. In the pancreatic lysate, SSTR1, 4 and 5 immunoreactivity decreases whereas SSTR3 immunoreactivity increases with no discernible changes in SSTR2 immunoreactivity. Furthermore, at the cellular level, R6/2 mice exhibit a receptor specific distributional pattern of SSTRs like immunoreactivity and colocalization with beta, alpha and delta cells. While GAD expression is increased, TH and SYP immunoreactivity was decreased in R6/2 mice, anticipating a cross-talk between the CNS and pancreas in diabetes pathophysiology. We also dissected out the changes in signaling pathway and found decreased activation and expression of PKA, AKT, ERK1/2 and STAT3 in R6/2 mice pancreas. These findings suggest that the impaired organization of SSTRs within islets may lead to perturbed hormonal regulation and signaling. These interconnected complex events might shed new light on the pathogenesis of diabetes in neurodegenerative diseases and the role of SSTRs in potential therapeutic intervention. |
