Leptin treatment confers clinical benefit at multiple stages of virally induced type 1 diabetes in BB rats

Annie J. Kruger; Chaoxing Yang; Kathryn L. Lipson; Stephen C. Pino; Jean H. Leif; Christopher M. Hogan; Barbara J. Whalen; Dennis L. Guberski; Young H Lee; Roger H Unger; Dale L. Greiner; Aldo A. Rossini; Rita Bortell

doi:10.3109/08916934.2010.482116

Leptin treatment confers clinical benefit at multiple stages of virally induced type 1 diabetes in BB rats

Annie J. Kruger, Chaoxing Yang, Kathryn L. Lipson, Stephen C. Pino, Jean H. Leif, Christopher M. Hogan, Barbara J. Whalen, Dennis L. Guberski, Young H Lee, Roger H Unger, Dale L. Greiner, Aldo A. Rossini, Rita Bortell

Research output: Contribution to journal › Article › peer-review

27 Scopus citations

Abstract

The adipokine, leptin, regulates blood glucose and the insulin secretory function of beta cells, while also modulating immune cell function. We hypothesized that the dual effects of leptin may prevent or suppress the autoreactive destruction of beta cells in a virally induced rodent model of type 1 diabetes. Nearly 100% of weanling BBDR rats treated with the combination of an innate immune system activator, polyinosinic:polycytidylic acid (pIC), and Kilham rat virus (KRV) become diabetic within a predictable time frame. We utilized this model to test the efficacy of leptin in preventing diabetes onset, remitting new onset disease, and preventing autoimmune recurrence in diabetic rats transplanted with syngeneic islet grafts. High doses of leptin delivered via an adenovirus vector (AdLeptin) or alzet pump prevented diabetes in>90% of rats treated with pIC+KRV. The serum hyperleptinemia generated by this treatment was associated with decreased body weight, decreased non-fasting serum insulin levels, and lack of islet insulitis in leptin-treated rats. In new onset diabetics, hyperleptinemia prevented rapid weight loss and diabetic ketoacidosis, and temporarily restored euglycemia. Leptin treatment also prolonged the survival of syngeneic islets transplanted into diabetic BBDR rats. In diverse therapeutic settings, we found leptin treatment to have significant beneficial effects in modulating virally induced diabetes. These findings merit further evaluation of leptin as a potential adjunct therapeutic agent for treatment of human type 1 diabetes.

Original language	English (US)
Pages (from-to)	137-148
Number of pages	12
Journal	Autoimmunity
Volume	44
Issue number	2
DOIs	https://doi.org/10.3109/08916934.2010.482116
State	Published - Mar 2011

Keywords

BB rat
Type 1 diabetes
islet transplantation
leptin
virus

ASJC Scopus subject areas

Immunology and Allergy
Immunology

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10.3109/08916934.2010.482116

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Kruger, A. J., Yang, C., Lipson, K. L., Pino, S. C., Leif, J. H., Hogan, C. M., Whalen, B. J., Guberski, D. L., Lee, Y. H., Unger, R. H., Greiner, D. L., Rossini, A. A., & Bortell, R. (2011). Leptin treatment confers clinical benefit at multiple stages of virally induced type 1 diabetes in BB rats. Autoimmunity, 44(2), 137-148. https://doi.org/10.3109/08916934.2010.482116

Leptin treatment confers clinical benefit at multiple stages of virally induced type 1 diabetes in BB rats. / Kruger, Annie J.; Yang, Chaoxing; Lipson, Kathryn L.; Pino, Stephen C.; Leif, Jean H.; Hogan, Christopher M.; Whalen, Barbara J.; Guberski, Dennis L.; Lee, Young H; Unger, Roger H; Greiner, Dale L.; Rossini, Aldo A.; Bortell, Rita.

In: Autoimmunity, Vol. 44, No. 2, 03.2011, p. 137-148.

Research output: Contribution to journal › Article › peer-review

Kruger, Annie J. ; Yang, Chaoxing ; Lipson, Kathryn L. ; Pino, Stephen C. ; Leif, Jean H. ; Hogan, Christopher M. ; Whalen, Barbara J. ; Guberski, Dennis L. ; Lee, Young H ; Unger, Roger H ; Greiner, Dale L. ; Rossini, Aldo A. ; Bortell, Rita. / Leptin treatment confers clinical benefit at multiple stages of virally induced type 1 diabetes in BB rats. In: Autoimmunity. 2011 ; Vol. 44, No. 2. pp. 137-148.

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abstract = "The adipokine, leptin, regulates blood glucose and the insulin secretory function of beta cells, while also modulating immune cell function. We hypothesized that the dual effects of leptin may prevent or suppress the autoreactive destruction of beta cells in a virally induced rodent model of type 1 diabetes. Nearly 100% of weanling BBDR rats treated with the combination of an innate immune system activator, polyinosinic:polycytidylic acid (pIC), and Kilham rat virus (KRV) become diabetic within a predictable time frame. We utilized this model to test the efficacy of leptin in preventing diabetes onset, remitting new onset disease, and preventing autoimmune recurrence in diabetic rats transplanted with syngeneic islet grafts. High doses of leptin delivered via an adenovirus vector (AdLeptin) or alzet pump prevented diabetes in>90% of rats treated with pIC+KRV. The serum hyperleptinemia generated by this treatment was associated with decreased body weight, decreased non-fasting serum insulin levels, and lack of islet insulitis in leptin-treated rats. In new onset diabetics, hyperleptinemia prevented rapid weight loss and diabetic ketoacidosis, and temporarily restored euglycemia. Leptin treatment also prolonged the survival of syngeneic islets transplanted into diabetic BBDR rats. In diverse therapeutic settings, we found leptin treatment to have significant beneficial effects in modulating virally induced diabetes. These findings merit further evaluation of leptin as a potential adjunct therapeutic agent for treatment of human type 1 diabetes.",

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note = "Funding Information: We thank Linda Leehy, Elaine Norowski, Cindy Bell, and Michael Bates for technical assistance. This was research supported in part by a grant from the ADA, an institutional Diabetes Endocrinology Research Center (DERC) grant DK32520 from the National Institutes of Health, the Beta Cell Biology Consortium, grants from the Juvenile Diabetes Research Foundation, International, the Brehm Foundation, and the Helms-ley Foundation. The contents of this publication are solely the responsibility of the authors and do not necessarily represent the official views of the NIH.",

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N1 - Funding Information: We thank Linda Leehy, Elaine Norowski, Cindy Bell, and Michael Bates for technical assistance. This was research supported in part by a grant from the ADA, an institutional Diabetes Endocrinology Research Center (DERC) grant DK32520 from the National Institutes of Health, the Beta Cell Biology Consortium, grants from the Juvenile Diabetes Research Foundation, International, the Brehm Foundation, and the Helms-ley Foundation. The contents of this publication are solely the responsibility of the authors and do not necessarily represent the official views of the NIH.

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Leptin treatment confers clinical benefit at multiple stages of virally induced type 1 diabetes in BB rats

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