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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...

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Autores principales: Denroche, Heather C., Quong, Whitney L., Bruin, Jennifer E., Tudurí, Eva, Asadi, Ali, Glavas, Maria M., Fox, Jessica K., Kieffer, Timothy J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Diabetes Association 2013
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.
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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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