Implanted islet mass influences the effects of dipeptidyl peptidase-IV inhibitor LAF237 on transplantation outcomes in diabetic mice

植入的胰岛质量影响二肽基肽酶 IV 抑制剂 LAF237 对糖尿病小鼠移植结果的影响

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作者:Jyuhn-Huarng Juang, Chen-Yi Chen, Chen-Wei Kao, Yu-Wen Huang, Tai-Yu Chiu, Chiung-Tong Chen

Background

Previous studies showed inconsistent

Conclusions

Our findings revealed 6-week treatment of LAF237 improves glucose tolerance and increases graft β-cell mass in diabetic mice transplanted with a sufficient number but not a marginal number of islets. These indicate that the effects of DPP-IV inhibitors are influenced by the implanted islet mass.

Methods

One hundred and fifty or three hundred islets were syngeneically transplanted under the renal capsule of each streptozocin-diabetic C57BL/6 mouse and recipients were then treated without or with LAF237 (10 mg/kg/day, po) for 6 weeks. After transplantation, recipients' blood glucose, body weight and intraperitoneal glucose tolerance test (IPGTT) were followed-up periodically. The graft was removed for the measurement of β-cell mass at 6 weeks.

Results

In recipients with 150 islets, it was not significantly different between the LAF237- treated group (n = 14) and control group (n = 14) in terms of the blood glucose, body weight, glucose tolerance at 2, 4 and 6 weeks or the graft β-cell mass at 6 weeks. In contrast, in recipients with 300 islets, the LAF237-treated group (n = 24) did have a lower area under the curve of the IPGTT at 4 weeks (p = 0.0237) and 6 weeks (p = 0.0113) as well as more graft β-cell mass at 6 weeks (0.655 ± 0.008 mg vs. 0.435 ± 0.006 mg, p = 0.0463) than controls (n = 24). Conclusions: Our findings revealed 6-week treatment of LAF237 improves glucose tolerance and increases graft β-cell mass in diabetic mice transplanted with a sufficient number but not a marginal number of islets. These indicate that the effects of DPP-IV inhibitors are influenced by the implanted islet mass.

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