Upregulation of non-β cell-derived vascular endothelial growth factor A increases small clusters of insulin-producing cells in the pancreas

Pancreatic β cell-derived vascular endothelial growth factor A (VEGF-A) contributes to normal β cell function. We therefore hypothesized that non-β cell-derived VEGF-A may affect its properties in adult mice.We generated transgenic mice expressing human VEGF-A (hVEGF-A) in a visceral smooth muscle c...

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Bibliographic Details
Published in:	Experimental and clinical endocrinology & diabetes Vol. 122; no. 5; p. 308
Main Authors:	Takenouchi, K, Shrestha, B, Yamakuchi, M, Yoshinaga, N, Arimura, N, Kawaguchi, H, Nagasato, T, Feil, R, Kawahara, K, Sakamoto, T, Maruyama, I, Hashiguchi, T
Format:	Journal Article
Language:	English
Published:	Germany 01-05-2014
Subjects:	Animals Diabetes Mellitus, Experimental - genetics Diabetes Mellitus, Experimental - metabolism Diabetes Mellitus, Experimental - pathology Humans Insulin - genetics Insulin - metabolism Insulin-Secreting Cells - metabolism Insulin-Secreting Cells - pathology Mice Mice, Transgenic Up-Regulation Vascular Endothelial Growth Factor A - biosynthesis Vascular Endothelial Growth Factor A - genetics
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Summary:	Pancreatic β cell-derived vascular endothelial growth factor A (VEGF-A) contributes to normal β cell function. We therefore hypothesized that non-β cell-derived VEGF-A may affect its properties in adult mice.We generated transgenic mice expressing human VEGF-A (hVEGF-A) in a visceral smooth muscle cell (SMC)-dominant manner under the control of the transgelin (Tagln/SM22α) promoter via a tamoxifen-induced Cre/loxP recombination system (SM-CreER(T2)/hVEGF mice).SM-CreER(T2)/hVEGF mice received tamoxifen orally followed by microscopic examination of their pancreas 4 weeks after the hVEGF-A induction. The number of clusters of insulin-producing cells (IPCs) in islets, pancreatic ducts, and individual IPCs were counted.The number of small IPC clusters (100-215 μm(2)) in the pancreas increased significantly in SM-CreER(T2)/hVEGF mice compared with SM-CreER(T2)(Ki) mice (473 out of 1 992 counts vs. 199 out of 976 counts, p<0.05), although total IPC area and the number of pancreatic duct IPCs, in proportion to exocrine area, were similar between the 2 groups. Although most small IPC clusters observed in SM-CreER(T2)/hVEGF mice were not accompanied by α and/or δ cells, some were attached to a single or a few α cells. An STZ-induced diabetic state in SM-CreER(T2)/hVEGF mice was slightly ameliorated, with only one point of significance 12 weeks after STZ administration, compared with SM-CreER(T2)(Ki) mice.Upregulation of non-β cell-derived VEGF-A may alter the composition of pancreatic IPCs by increasing the number of small IPC clusters. These findings provide new information on the role of non-β cell-derived VEGF-A to IPC regeneration and insulin production.
ISSN:	1439-3646
DOI:	10.1055/s-0034-1371811