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Exp Clin Endocrinol Diabetes 2014; 122(05): 308-315
DOI: 10.1055/s-0034-1371811
Article
© J. A. Barth Verlag in Georg Thieme Verlag KG Stuttgart · New York

Upregulation of non-β Cell-derived Vascular Endothelial Growth Factor A Increases Small Clusters of Insulin-producing Cells in the Pancreas

K. Takenouchi
1   Department of Laboratory and Vascular Medicine, Graduate School of Medical and Dental Sciences, Kagoshima University, Sakuragaoka, Kagoshima, Japan
,
B. Shrestha
1   Department of Laboratory and Vascular Medicine, Graduate School of Medical and Dental Sciences, Kagoshima University, Sakuragaoka, Kagoshima, Japan
,
M. Yamakuchi
1   Department of Laboratory and Vascular Medicine, Graduate School of Medical and Dental Sciences, Kagoshima University, Sakuragaoka, Kagoshima, Japan
,
N. Yoshinaga
2   Department of Ophthalmology, Graduate School of Medical and Dental Sciences, Kagoshima University, Sakuragaoka, Kagoshima, Japan
,
N. Arimura
2   Department of Ophthalmology, Graduate School of Medical and Dental Sciences, Kagoshima University, Sakuragaoka, Kagoshima, Japan
,
H. Kawaguchi
3   Department of Veterinary Experimental Animal Science, Faculty of Agriculture, Kagoshima University, Korimoto, Kagoshima, Japan
,
T. Nagasato
4   Systems Biology in Thromboregulation, Graduate School of Medical and Dental Sciences, Kagoshima University, Sakuragaoka, Kagoshima, Japan
,
R. Feil
5   Interfakultäres Institut für Biochemie, University of Tübingen, Tübingen, Germany
,
K. Kawahara
6   Laboratory of Functional Foods, Department of Biomedical Engineering Osaka Institute of Technology, Osaka, Japan
,
T. Sakamoto
2   Department of Ophthalmology, Graduate School of Medical and Dental Sciences, Kagoshima University, Sakuragaoka, Kagoshima, Japan
,
I. Maruyama
4   Systems Biology in Thromboregulation, Graduate School of Medical and Dental Sciences, Kagoshima University, Sakuragaoka, Kagoshima, Japan
,
T. Hashiguchi
1   Department of Laboratory and Vascular Medicine, Graduate School of Medical and Dental Sciences, Kagoshima University, Sakuragaoka, Kagoshima, Japan
› Author Affiliations
Further Information

Publication History

received 06 February 2014
first decision 06 February 2014

accepted 26 February 2014

Publication Date:
16 May 2014 (online)

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Abstract

Background:

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.

Methods:

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-CreERT2/hVEGF mice).

SM-CreERT2/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.

Results:

The number of small IPC clusters (100–215 μm2) in the pancreas increased significantly in SM-CreERT2/hVEGF mice compared with SM-CreERT2(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-CreERT2/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-CreERT2/hVEGF mice was slightly ameliorated, with only one point of significance 12 weeks after STZ administration, compared with SM-CreERT2(Ki) mice.

Conclusion:

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.

Key words

diabetes - islet - smooth muscle cell - streptozotocin
 

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