| First Author | Lavine JA | Year | 2015 |
| Journal | Am J Physiol Endocrinol Metab | Volume | 309 |
| Issue | 10 | Pages | E819-28 |
| PubMed ID | 26394663 | Mgi Jnum | J:229691 |
| Mgi Id | MGI:5753007 | Doi | 10.1152/ajpendo.00159.2015 |
| Citation | Lavine JA, et al. (2015) Cholecystokinin expression in the beta-cell leads to increased beta-cell area in aged mice and protects from streptozotocin-induced diabetes and apoptosis. Am J Physiol Endocrinol Metab 309(10):E819-28 |
| abstractText | Cholecystokinin (CCK) is a peptide hormone produced in the gut and brain with beneficial effects on digestion, satiety, and insulin secretion. CCK is also expressed in pancreatic beta-cells, but only in models of obesity and insulin resistance. Whole body deletion of CCK in obese mice leads to reduced beta-cell mass expansion and increased apoptosis. We hypothesized that islet-derived CCK is important in protection from beta-cell apoptosis. To determine the specific role of beta-cell-derived CCK in beta-cell mass dynamics, we generated a transgenic mouse that expresses CCK in the beta-cell in the lean state (MIP-CCK). Although this transgene contains the human growth hormone minigene, we saw no expression of human growth hormone protein in transgenic islets. We examined the ability of MIP-CCK mice to maintain beta-cell mass when subjected to apoptotic stress, with advanced age, and after streptozotocin treatment. Aged MIP-CCK mice have increased beta-cell area. MIP-CCK mice are resistant to streptozotocin-induced diabetes and exhibit reduced beta-cell apoptosis. Directed CCK overexpression in cultured beta-cells also protects from cytokine-induced apoptosis. We have identified an important new paracrine/autocrine effect of CCK in protection of beta-cells from apoptotic stress. Understanding the role of beta-cell CCK adds to the emerging knowledge of classic gut peptides in intraislet signaling. CCK receptor agonists are being investigated as therapeutics for obesity and diabetes. While these agonists clearly have beneficial effects on body weight and insulin sensitivity in peripheral tissues, they may also directly protect beta-cells from apoptosis. |
