| Autor: |
Jetton, Thomas L., Everill, Brian, Lausier, James, Roskens, Violet, Habibovic, Aida, Larock, Kyla, Gokin, Alexander, Peshavaria, Mina, Leahy, Jack L. |
| Předmět: |
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| Zdroj: |
American Journal of Physiology: Endocrinology & Metabolism; Apr2008, Vol. 294, pE679-E687, 9p, 7 Graphs |
| Abstrakt: |
The physiological mechanisms underlying pancreatic β-cell mass (BCM) homeostasis are complex and not fully resolved. Here we examined the factors contributing to the increased BCM following a mild glucose infusion (GI) whereby normoglycemia was maintained through 96 h. We used morphometric and immunochemical methods to investigate enhanced β-cell growth and survival in Sprague-Dawley rats. BCM was elevated >2.5-fold over saline-infused control rats by 48 h and increased modestly thereafter. Unexpectedly, increases in β-cell proliferation were not observed at any time point through 4 days. Instead, enhanced numbers of insuIin+ cell clusters and small islets (400-12,000 µm² ~23- to 124-µm diameter), mostly scattered among the acini, were observed in the GI rats by 48 h despite no difference in the numbers of medium to large islets. We previously showed that increased β-cell growth in rodent models of insulin resistance and pancreatic regeneration involves increased activated Akt/PKB, a key β-cell signaling intermediate, in both islets and endocrine cell clusters. GI in normal rats also leads to increased Akt activation in islet β-cells, as well as in insulin+ and insulin cells in the common duct epithelium and endocrine clusters. This correlated with strong Pdx1 expression in these same cells. These results suggest that mechanisms other than proliferation underlie the rapid β-cell growth response following a mild GI in the normal rat and involve Akt-regulated enhanced β-cell survival potential and neogenesis from epithelial precursors. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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