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Improved Outcome of Islet Transplantation in Partially Pancreatectomized Diabetic Mice by Inhibition of Dipeptidyl Peptidase-4 With Sitagliptin

Kim, Young-Seok MS*; Oh, Seung-Hoon BS; Park, Ki-Soo PhD*; No, Heesung MS; Oh, Bae-Jun MS*; Kim, Soo Kyoung MD; Jung, Hye Seung MD, PhD; Kim, Jae-Hyeon MD, PhD*†; Lee, Myung-Shik MD, PhD*†; Lee, Moon-Kyu MD, PhD*†; Kim, Kwang-Won MD, PhD*†

doi: 10.1097/MPA.0b013e318214832d
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Objective: Glucagon-like peptide-1 (GLP-1) is known to promote beta cell proliferation, and dipeptidyl peptidase-4 (DPP-4) inhibitor increases GLP-1 levels by preventing its degradation. This study was designed to evaluate the effects of sitagliptin (sita), a DPP-4 inhibitor, on the outcome of islet transplantation (ITx) in diabetic mice after partial pancreatectomy (Px).

Methods: A diabetic mouse model was prepared by performing 70% Px in C57BL/6 mice. The diabetic mice were treated with sita, subjected to ITx, or both treated with sita and subjected to ITx. After 12 days of sita treatment, the pancreatic remnants and transplanted islets were histologically examined.

Results: Dipeptidyl peptidase-4 inhibitor increased the concentration of plasma active GLP-1 regardless of ITx and improved glycemic control in the ITx group. The beta cell mass of the pancreatic remnants increased in the ITx group, and mice that received combined treatment with ITx and sita showed a greater increase in the beta cell mass. Dipeptidyl peptidase-4 inhibitor seems to induce proliferation and inhibit apoptosis of beta cells in pancreatic remnants.

Conclusions: The DPP-4 inhibitor favorably affects ITx in partially pancreatectomized diabetic mice by increasing the beta cell mass through cell proliferation and inhibition of beta cell apoptosis.

Supplemental Digital Content is available in the text.

From the *Department of Molecular Medicine, Sungkyunkwan University School of Medicine; †Division of Endocrinology and Metabolism, Department of Medicine, Samsung Medical Center; and ‡Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.

Received for publication July 1, 2010; accepted February 7, 2011.

Reprints: Kwang-Won Kim, MD, PhD, Division of Endocrinology and Metabolism, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-dong, Gangnam-gu, Seoul 135-710, Republic of Korea (e-mail: kw1234@skku.edu).

This research was supported in part by a research grant from the Investigator Initiated Study Program, Merck, the Korea Health 21 R&D Project, Ministry of Health & Welfare, Republic of Korea (A080009), the Samsung Biomedical Research Institute (C-A6-405) grant, the Korean Ministry of Education, Science and Technology, and the IN-SUNG Foundation for Medical Research.

Supplemental digital contents are available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Web site (www.pancreasjournal.com).

© 2011 Lippincott Williams & Wilkins, Inc.