Leptin gene therapy in the fight against diabetes.
BACKGROUND
The incidence of diabetes is increasing worldwide, yet current treatments are not always effective for all patient or disease types.


METHODS
Here, we summarize the biologic and clinical roles of leptin in diabetes, and discuss candidate viral vectors that may be employed in the clinical use of central leptin gene therapy for diabetes.


RESULTS
We discuss how studies on leptin, a regulator of the insulin-glucose axis, have significantly advanced our understanding of the roles of energy homeostasis and insulin resistance in the pathogeneses of metabolic syndrome and diabetes. Recent studies have demonstrated the long-term therapeutic effects of central leptin gene therapy in obesity and diabetes via decreased insulin resistance and increased glucose metabolism. Many of these studies have employed viral vectors, which afford high in vivo gene transduction efficiencies compared with non-viral vectors.


CONCLUSIONS
Adeno-associated viral vectors are particularly well suited for central leptin gene therapy owing to their low toxicity and ability to drive transgene expression for extended periods.
Wang
Yuqing
Y
Kagoshima University Graduate School of Medical and Dental Sciences, Department of Gene Therapy and Regenerative Medicine, 8-35-1 Sakuragaoka, Kagoshima 890-8544, Japan.
Asakawa
Akihiro
A
Inui
Akio
A
Kosai
Ken-ichiro
K
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D000229:Dependovirus / Q000235:genetics; D003920:Diabetes Mellitus / Q000235:genetics / Q000378:metabolism / Q000628:therapy*; D015316:Genetic Therapy / Q000009:adverse effects; D005822:Genetic Vectors; D006801:Humans; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D020738:Leptin / Q000235:genetics / Q000378:metabolism*; D016896:Treatment Outcome
D001786:Blood Glucose; D007328:Insulin; D020738:Leptin