{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T02:35:53Z","timestamp":1760236553463,"version":"build-2065373602"},"reference-count":45,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2021,12,7]],"date-time":"2021-12-07T00:00:00Z","timestamp":1638835200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["IBN 0236385"],"award-info":[{"award-number":["IBN 0236385"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["NIH R01AG 027697"],"award-info":[{"award-number":["NIH R01AG 027697"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Type 1 diabetes (T1D) is characterized by hyperphagia, hyperglycemia and activation of the hypothalamic\u2013pituitary\u2013adrenal (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.<\/jats:p>","DOI":"10.3390\/ijms222413197","type":"journal-article","created":{"date-parts":[[2021,12,7]],"date-time":"2021-12-07T20:23:21Z","timestamp":1638908601000},"page":"13197","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Evaluation of the Central Effects of Systemic Lentiviral-Mediated Leptin Delivery in Streptozotocin-Induced Diabetic Rats"],"prefix":"10.3390","volume":"22","author":[{"given":"Kimberly A.","family":"Clark","sequence":"first","affiliation":[{"name":"Neuroscience Graduate Program, Michigan State University, E. Lansing, MI 48824, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4748-5135","authenticated-orcid":false,"given":"Andrew C.","family":"Shin","sequence":"additional","affiliation":[{"name":"Neurobiology of Nutrition Laboratory, Department of Nutritional Sciences, College of Human Sciences, Texas Tech University, Lubbock, TX 79409, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Madhu P.","family":"Sirivelu","sequence":"additional","affiliation":[{"name":"Pathobiology and Diagnostic Investigation, Michigan State University, E. Lansing, MI 48824, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ramya C.","family":"MohanKumar","sequence":"additional","affiliation":[{"name":"Neuroendocrine Research Laboratory, University of Georgia, Athens, GA 30602, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sreenivasa R.","family":"Maddineni","sequence":"additional","affiliation":[{"name":"Department of Poultry Science, College of Agricultural Sciences, The Pennsylvania State University, University Park, PA 16802, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ramesh","family":"Ramachandran","sequence":"additional","affiliation":[{"name":"Department of Poultry Science, College of Agricultural Sciences, The Pennsylvania State University, University Park, PA 16802, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Puliyur S.","family":"MohanKumar","sequence":"additional","affiliation":[{"name":"Neuroscience Graduate Program, Michigan State University, E. Lansing, MI 48824, USA"},{"name":"Pathobiology and Diagnostic Investigation, Michigan State University, E. Lansing, MI 48824, USA"},{"name":"Neuroendocrine Research Laboratory, University of Georgia, Athens, GA 30602, USA"},{"name":"Department of Biomedical Sciences, University of Georgia, Athens, GA 30602, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3365-7864","authenticated-orcid":false,"given":"Sheba M. J.","family":"MohanKumar","sequence":"additional","affiliation":[{"name":"Neuroscience Graduate Program, Michigan State University, E. Lansing, MI 48824, USA"},{"name":"Neuroendocrine Research Laboratory, University of Georgia, Athens, GA 30602, USA"},{"name":"Department of Biomedical Sciences, University of Georgia, Athens, GA 30602, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,12,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"586","DOI":"10.1177\/1535370218761662","article-title":"Targeting dysfunctional beta-cell signaling for the potential treatment of type 1 diabetes mellitus","volume":"243","author":"Fenske","year":"2018","journal-title":"Exp. Biol. 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