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 | |
| State | Published - Mar 2011 |
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Keywords
- BB rat
- islet transplantation
- leptin
- Type 1 diabetes
- virus
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology
Cite this
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
}
TY - JOUR
T1 - Leptin treatment confers clinical benefit at multiple stages of virally induced type 1 diabetes in BB rats
AU - Kruger, Annie J.
AU - Yang, Chaoxing
AU - Lipson, Kathryn L.
AU - Pino, Stephen C.
AU - Leif, Jean H.
AU - Hogan, Christopher M.
AU - Whalen, Barbara J.
AU - Guberski, Dennis L.
AU - Lee, Young H
AU - Unger, Roger H
AU - Greiner, Dale L.
AU - Rossini, Aldo A.
AU - Bortell, Rita
PY - 2011/3
Y1 - 2011/3
N2 - 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.
AB - 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.
KW - BB rat
KW - islet transplantation
KW - leptin
KW - Type 1 diabetes
KW - virus
UR - http://www.scopus.com/inward/record.url?scp=79551569614&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=79551569614&partnerID=8YFLogxK
U2 - 10.3109/08916934.2010.482116
DO - 10.3109/08916934.2010.482116
M3 - Article
C2 - 20695765
AN - SCOPUS:79551569614
VL - 44
SP - 137
EP - 148
JO - Autoimmunity
JF - Autoimmunity
SN - 0891-6934
IS - 2
ER -