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Neuroendocrine Dysfunction in Streptozocin‐induced Diabetes is Ameliorated with Leptin Lentiviral Vector Transfection.
Author(s) -
Clark Kimberly Ann,
Shin Andrew Changhun,
Sirivelu Madhu P.,
MohanKumar Sheba M.J.,
MohanKumar Puliyur S.
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a1250-d
Subject(s) - leptin , medicine , endocrinology , diabetes mellitus , hypothalamus , streptozocin , leptin receptor , streptozotocin , obesity
Diabetes is characterized by several neuroendocrine complications. There is a reduction in serum leptin levels which causes an increase in norepinephrine (NE) in the paraventricular nucleus (PVN) of the hypothalamus leading to stress axis activation. To investigate leptin’s role in diabetes, we constructed a human immunodeficiency virus type 1 lentiviral vector that encoded either leptin (LV‐leptin) or control green fluorescence protein (LV‐GFP) genes and transfected adult male Sprague Dawley rats. Seven days later, animals were treated with vehicle or STZ (65mg/kg bw). At the end of the treatment, animals were sacrificed and their brains were removed. Serum was assayed for leptin and corticosterone (CS) using RIA. LV‐leptin treated animals had significantly lower blood glucose levels (Mean±SE; mg/dl; 414±13) compared to controls (499.3±6) and LV‐GFP treated animals (513±13.5). Serum leptin levels were higher in LV‐leptin treated animals compared to controls and LV‐GFP animals. CS levels (Mean±SE, ng/ml) were significantly lower in LV‐leptin rats (164.85±32.5) compared to controls (321.6±72) and LV‐GFP treated rats (331.6±97). This was accompanied by reductions in NE levels in the PVN of LV‐Leptin treated rats compared to the control and LV‐GFP groups. These results indicate that leptin gene transfer attenuates neuroendocrine dysfunction in an STZ‐induced diabetic model. Supported by NIH AG 027697.