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 journalArticle

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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.

Original languageEnglish (US)
Pages (from-to)137-148
Number of pages12
JournalAutoimmunity
Volume44
Issue number2
DOIs
StatePublished - Mar 2011

Fingerprint

Inbred BB Rats
Leptin
Type 1 Diabetes Mellitus
Parvovirus
Insulin
Poly C
Poly I-C
Diabetic Ketoacidosis
Adipokines
Serum
Adenoviridae
Autoimmune Diseases
Blood Glucose
Weight Loss
Immune System
Rodentia
Body Weight
Transplants
Recurrence
Survival

Keywords

  • BB rat
  • islet transplantation
  • leptin
  • Type 1 diabetes
  • virus

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Kruger, A. J., Yang, C., Lipson, K. L., Pino, S. C., Leif, J. H., Hogan, C. M., ... 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 journalArticle

Kruger, AJ, Yang, C, Lipson, KL, Pino, SC, Leif, JH, Hogan, CM, Whalen, BJ, Guberski, DL, Lee, YH, Unger, RH, Greiner, DL, Rossini, AA & Bortell, R 2011, 'Leptin treatment confers clinical benefit at multiple stages of virally induced type 1 diabetes in BB rats', Autoimmunity, vol. 44, no. 2, pp. 137-148. https://doi.org/10.3109/08916934.2010.482116
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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