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- Title
Enhancing Pancreatic Beta-Cell Regeneration <i>In Vivo</i> with Pioglitazone and Alogliptin.
- Authors
Yin, Hao; Park, Soo-Young; Wang, Xiao-Jun; Misawa, Ryosuke; Grossman, Eric J.; Tao, Jing; Zhong, Rong; Witkowski, Piotr; Bell, Graeme I.; Chong, Anita S.
- Abstract
Aims/Hypothesis: Pancreatic beta-cells retain limited ability to regenerate and proliferate after various physiologic triggers. Identifying therapies that are able to enhance beta-cell regeneration may therefore be useful for the treatment of both type 1 and type 2 diabetes. Methods: In this study we investigated endogenous and transplanted beta-cell regeneration by serially quantifying changes in bioluminescence from beta-cells from transgenic mice expressing firefly luciferase under the control of the mouse insulin I promoter. We tested the ability of pioglitazone and alogliptin, two drugs developed for the treatment of type 2 diabetes, to enhance beta-cell regeneration, and also defined the effect of the immunosuppression with rapamycin and tacrolimus on transplanted islet beta mass. Results: Pioglitazone is a stimulator of nuclear receptor peroxisome proliferator-activated receptor gamma while alogliptin is a selective dipeptidyl peptidase IV inhibitor. Pioglitazone alone, or in combination with alogliptin, enhanced endogenous beta-cell regeneration in streptozotocin-treated mice, while alogliptin alone had modest effects. In a model of syngeneic islet transplantation, immunosuppression with rapamycin and tacrolimus induced an early loss of beta-cell mass, while treatment with insulin implants to maintain normoglycemia and pioglitazone plus alogliptin was able to partially promote beta-cell mass recovery. Conclusions/Interpretation: These data highlight the utility of bioluminescence for serially quantifying functional beta-cell mass in living mice. They also demonstrate the ability of pioglitazone, used either alone or in combination with alogliptin, to enhance regeneration of endogenous islet beta-cells as well as transplanted islets into recipients treated with rapamycin and tacrolimus.
- Subjects
PANCREATIC regeneration; PANCREATIC beta cells; PIOGLITAZONE; LABORATORY mice; IMMUNOSUPPRESSION; BIOLUMINESCENCE; ISLANDS of Langerhans transplantation; ENDOCRINOLOGY
- Publication
PLoS ONE, 2013, Vol 8, Issue 6, p1
- ISSN
1932-6203
- Publication type
Article
- DOI
10.1371/journal.pone.0065777