Evaluation of the Central Effects of Systemic Lentiviral-Mediated Leptin Delivery in Streptozotocin-Induced Diabetic Rats

dc.creatorClark, Kimberly A.
dc.creatorShin, Andrew C. (TTU)
dc.creatorSirivelu, Madhu P.
dc.creatorMohanKumar, Ramya C.
dc.creatorMaddineni, Sreenivasa R.
dc.creatorRamachandran, Ramesh
dc.creatorMohanKumar, Puliyur S.
dc.creatorMohanKumar, Sheba M.J.
dc.date.accessioned2022-05-09T20:22:29Z
dc.date.available2022-05-09T20:22:29Z
dc.date.issued2021
dc.description© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).en_US
dc.description.abstractType 1 diabetes (T1D) is characterized by hyperphagia, hyperglycemia and activation of the hypothalamic–pituitary–adrenal (HPA) axis. We have reported previously that daily leptin injections help to alleviate these symptoms. Therefore, we hypothesized that leptin gene therapy could help to normalize the neuroendocrine dysfunction seen in T1D. Adult male Sprague Dawley rats were injected i.v. with a lentiviral vector containing the leptin gene or green fluorescent protein. Ten days later, they were injected with the vehicle or streptozotocin (STZ). HPA function was assessed by measuring norepinephrine (NE) levels in the paraventricular nucleus (PVN) and serum corticosterone (CS). Treatment with the leptin lentiviral vector (Lepvv) increased leptin and insulin levels in non-diabetic rats, but not in diabetic animals. There was a significant reduction in blood glucose levels in diabetic rats due to Lepvv treatment. Both NE levels in the PVN and serum CS were reduced in diabetic rats treated with Lepvv. Results from this study provide evidence that leptin gene therapy in STZ-induced diabetic rats was able to partially normalize some of the neuroendocrine abnormalities, but studies with higher doses of the Lepvv are needed to develop this into a viable option for treating T1D.en_US
dc.identifier.citationClark KA, Shin AC, Sirivelu MP, MohanKumar RC, Maddineni SR, Ramachandran R, MohanKumar PS, MohanKumar SMJ. Evaluation of the Central Effects of Systemic Lentiviral-Mediated Leptin Delivery in Streptozotocin-Induced Diabetic Rats. International Journal of Molecular Sciences. 2021; 22(24):13197. https://doi.org/10.3390/ijms222413197en_US
dc.identifier.urihttps://doi.org/10.3390/ijms222413197
dc.identifier.urihttps://hdl.handle.net/2346/89167
dc.language.isoengen_US
dc.subjectDiabetesen_US
dc.subjectLeptinen_US
dc.subjectStressen_US
dc.subjectHypothalamusen_US
dc.subjectNorepinephrineen_US
dc.subjectCorticosteroneen_US
dc.subjectGene Transferen_US
dc.titleEvaluation of the Central Effects of Systemic Lentiviral-Mediated Leptin Delivery in Streptozotocin-Induced Diabetic Ratsen_US
dc.typeArticleen_US

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