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Leptin Administration Enhances Islet Transplant Performance in Diabetic Mice
Islet transplantation is an effective method to obtain long-term glycemic control for patients with type 1 diabetes, yet its widespread use is limited by an inadequate supply of donor islets. The hormone leptin has profound glucose-lowering and insulin-sensitizing action in type 1 diabetic rodent mo...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Diabetes Association
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3717838/ https://www.ncbi.nlm.nih.gov/pubmed/23656888 http://dx.doi.org/10.2337/db12-1684 |
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author | Denroche, Heather C. Quong, Whitney L. Bruin, Jennifer E. Tudurí, Eva Asadi, Ali Glavas, Maria M. Fox, Jessica K. Kieffer, Timothy J. |
author_facet | Denroche, Heather C. Quong, Whitney L. Bruin, Jennifer E. Tudurí, Eva Asadi, Ali Glavas, Maria M. Fox, Jessica K. Kieffer, Timothy J. |
author_sort | Denroche, Heather C. |
collection | PubMed |
description | Islet transplantation is an effective method to obtain long-term glycemic control for patients with type 1 diabetes, yet its widespread use is limited by an inadequate supply of donor islets. The hormone leptin has profound glucose-lowering and insulin-sensitizing action in type 1 diabetic rodent models. We hypothesized that leptin administration could reduce the dose of transplanted islets required to achieve metabolic control in a mouse model of type 1 diabetes. We first performed a leptin dose-response study in C57Bl/6 mice with streptozotocin (STZ)-induced diabetes to determine a leptin dose insufficient to reverse hyperglycemia. Subsequently, we compared the ability of suboptimal islet transplants of 50 or 125 syngeneic islets to achieve glycemic control in STZ-induced diabetic C57Bl/6 mice treated with or without this dose of leptin. The dose-response study revealed that leptin reverses STZ-induced diabetes in a dose-dependent manner. Supraphysiological leptin levels were necessary to restore euglycemia but simultaneously increased risk of hypoglycemia, and also lost efficacy after 12 days of administration. In contrast, 1 µg/day leptin only modestly reduced blood glucose but maintained efficacy throughout the study duration. We then administered 1 µg/day leptin to diabetic mice that underwent transplantation of 50 or 125 islets. Although these islet doses were insufficient to ameliorate hyperglycemia alone, coadministration of leptin with islet transplantation robustly improved control of glucose and lipid metabolism, without increasing circulating insulin levels. This study reveals that low-dose leptin administration can reduce the number of transplanted islets required to achieve metabolic control in STZ-induced diabetic mice. |
format | Online Article Text |
id | pubmed-3717838 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | American Diabetes Association |
record_format | MEDLINE/PubMed |
spelling | pubmed-37178382014-08-01 Leptin Administration Enhances Islet Transplant Performance in Diabetic Mice Denroche, Heather C. Quong, Whitney L. Bruin, Jennifer E. Tudurí, Eva Asadi, Ali Glavas, Maria M. Fox, Jessica K. Kieffer, Timothy J. Diabetes Original Research Islet transplantation is an effective method to obtain long-term glycemic control for patients with type 1 diabetes, yet its widespread use is limited by an inadequate supply of donor islets. The hormone leptin has profound glucose-lowering and insulin-sensitizing action in type 1 diabetic rodent models. We hypothesized that leptin administration could reduce the dose of transplanted islets required to achieve metabolic control in a mouse model of type 1 diabetes. We first performed a leptin dose-response study in C57Bl/6 mice with streptozotocin (STZ)-induced diabetes to determine a leptin dose insufficient to reverse hyperglycemia. Subsequently, we compared the ability of suboptimal islet transplants of 50 or 125 syngeneic islets to achieve glycemic control in STZ-induced diabetic C57Bl/6 mice treated with or without this dose of leptin. The dose-response study revealed that leptin reverses STZ-induced diabetes in a dose-dependent manner. Supraphysiological leptin levels were necessary to restore euglycemia but simultaneously increased risk of hypoglycemia, and also lost efficacy after 12 days of administration. In contrast, 1 µg/day leptin only modestly reduced blood glucose but maintained efficacy throughout the study duration. We then administered 1 µg/day leptin to diabetic mice that underwent transplantation of 50 or 125 islets. Although these islet doses were insufficient to ameliorate hyperglycemia alone, coadministration of leptin with islet transplantation robustly improved control of glucose and lipid metabolism, without increasing circulating insulin levels. This study reveals that low-dose leptin administration can reduce the number of transplanted islets required to achieve metabolic control in STZ-induced diabetic mice. American Diabetes Association 2013-08 2013-07-17 /pmc/articles/PMC3717838/ /pubmed/23656888 http://dx.doi.org/10.2337/db12-1684 Text en © 2013 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details. |
spellingShingle | Original Research Denroche, Heather C. Quong, Whitney L. Bruin, Jennifer E. Tudurí, Eva Asadi, Ali Glavas, Maria M. Fox, Jessica K. Kieffer, Timothy J. Leptin Administration Enhances Islet Transplant Performance in Diabetic Mice |
title | Leptin Administration Enhances Islet Transplant Performance in Diabetic Mice |
title_full | Leptin Administration Enhances Islet Transplant Performance in Diabetic Mice |
title_fullStr | Leptin Administration Enhances Islet Transplant Performance in Diabetic Mice |
title_full_unstemmed | Leptin Administration Enhances Islet Transplant Performance in Diabetic Mice |
title_short | Leptin Administration Enhances Islet Transplant Performance in Diabetic Mice |
title_sort | leptin administration enhances islet transplant performance in diabetic mice |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3717838/ https://www.ncbi.nlm.nih.gov/pubmed/23656888 http://dx.doi.org/10.2337/db12-1684 |
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