| First Author | Bando M | Year | 2013 |
| Journal | Am J Physiol Endocrinol Metab | Volume | 305 |
| Issue | 1 | Pages | E140-8 |
| PubMed ID | 23651849 | Mgi Jnum | J:199276 |
| Mgi Id | MGI:5501398 | Doi | 10.1152/ajpendo.00112.2013 |
| Citation | Bando M, et al. (2013) Overexpression of intraislet ghrelin enhances beta-cell proliferation after streptozotocin-induced beta-cell injury in mice. Am J Physiol Endocrinol Metab 305(1):E140-8 |
| abstractText | Previously, we reported that exogenous administration of ghrelin ameliorates glucose metabolism in a neonate streptozotocin (STZ)-induced diabetic rat model through enhancement of beta-cell proliferation. However, it was not clear whether the observed beta-cell proliferation was a direct or indirect effect (e.g., via orexigenic or growth hormone-stimulated pathways) of ghrelin activity. Here, we aimed to investigate whether ghrelin directly impacts beta-cell proliferation after STZ-induced injury in mice. Seven-week-old male rat insulin II promoter-ghrelin internal ribosomal sequence ghrelin O-acyltransferase transgenic (RIP-GG Tg) mice, which have elevated pancreatic ghrelin levels, but only minor changes in plasma ghrelin levels when fed a medium-chain triglyceride-rich diet, were treated with STZ. Then, serum insulin, pancreatic insulin mRNA expression, and islet histology were evaluated. We found that the serum insulin levels, but not blood glucose levels, of RIP-GG Tg mice were significantly ameliorated 14 days post-STZ treatment. Pancreatic insulin mRNA expression was significantly elevated in RIP-GG Tg mice, and beta-cell numbers in islets were increased. Furthermore, the number of phospho-histone H3(+) or Ki67(+) proliferating beta-cells was significantly elevated in RIP-GG Tg mice, whereas the apoptotic indexes within the islets, as determined by TUNEL assay, were not changed. These results indicate that ghrelin can directly stimulate beta-cell proliferation in vivo after beta-cell injury even without its orexigenic or GH-stimulating activities, although it did not have enough impact to normalize the glucose tolerance in adult mice. |
