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Updated: Jul 11, 2026
Neo-Islet Formation in Liver of Diabetic Mice by Helper-dependent Adenoviral Vector-Mediated Gene Transfer
Published on: October 10, 2012
Adiponectin gene therapy of streptozotocin-induced diabetic mice using hydrodynamic injection
Masayoshi Fukushima1, Yoshiyuki Hattori, Hideo Tsukada
1Institute of Medicinal Chemistry, Hoshi University, Shinagawa-ku, Tokyo 142-8501, Japan.
Background:
Adiponectin (Adipo), an adipocyte hormone involved in the regulation of glucose and lipid metabolism, has already been identified as a potential therapeutic target for the treatment of diabetes. However, successful delivery of Adipo to the receptors is difficult due to their peptide characteristics. Receptors for Adipo are abundantly expressed in the liver and skeletal muscle.
Methods:
Uptake of 2-(N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)-2-deoxyglucose (2-NBDG) in hepatoblastoma HepG2 cells expressing Adipo was examined. Adipo-expressing plasmid DNA (10-50 microg) in saline solution (0.1 ml/g body weight) was rapidly injected into the tail vein of 4-week-old diabetic mice after 4-6 weeks of treatment with streptozotocin (STZ). Uptake of glucose in diabetic mice also was measured using a planar positron imaging system featuring 18-fluorodeoxyglucose.
Results:
HepG2 cells expressing Adipo exhibited significantly increased 2-NBDG uptake compared with cells transfected with control plasmid even in the absence of insulin. STZ-induced diabetic mice showed decreased serum Adipo levels compared with non-diabetic mice. A single hydrodynamic injection of 10-50 microg Adipo-expressing plasmid DNA into diabetic mice led to approximately 10-15-fold elevation in serum Adipo levels, and resulted in decreased serum levels of glucose and triglyceride. As well as exhibiting higher levels of Adipo expression, diabetic mice also had higher hepatic glucose uptake than similar mice injected with control plasmid.
Conclusions:
We report that STZ-induced diabetic mice exhibited decreased Adipo levels and hyperglycemia which may be alleviated by hydrodynamic injection of the Adipo gene. This type of gene delivery system to the liver offers a different approach in developing novel treatments for type 1 and 2 diabetes.
Insights
Gene therapy using adiponectin (Adipo) gene injection effectively lowered blood glucose and triglyceride levels in diabetic mice. This novel liver gene delivery system shows promise for treating type 1 and type 2 diabetes.
Area of Science:
- Metabolic research
- Gene therapy
- Diabetes mellitus
Background:
- Adiponectin (Adipo) is a key hormone regulating glucose and lipid metabolism, implicated as a therapeutic target for diabetes.
- Challenges exist in delivering Adipo due to its peptide nature, despite abundant receptors in liver and muscle.
- Streptozotocin (STZ)-induced diabetic mice exhibit reduced Adipo levels and hyperglycemia.
Purpose of the Study:
- To investigate the efficacy of Adipo gene delivery via hydrodynamic injection in a mouse model of diabetes.
- To assess the impact of Adipo gene therapy on glucose and lipid metabolism in diabetic mice.
Main Methods:
- Examined 2-NBDG glucose uptake in Adipo-expressing HepG2 cells.
- Administered Adipo-expressing plasmid DNA via hydrodynamic tail vein injection to STZ-induced diabetic mice.
- Measured serum Adipo, glucose, triglyceride levels, and hepatic glucose uptake using 18-fluorodeoxyglucose PET imaging.
Main Results:
- Adipo-expressing HepG2 cells showed increased glucose uptake independent of insulin.
- Hydrodynamic injection of Adipo gene significantly elevated serum Adipo levels (10-15 fold) in diabetic mice.
- Diabetic mice treated with Adipo gene demonstrated reduced serum glucose, triglyceride levels, and increased hepatic glucose uptake.
Conclusions:
- STZ-induced diabetes is characterized by decreased Adipo levels and hyperglycemia, which can be ameliorated by Adipo gene therapy.
- Liver-directed hydrodynamic gene delivery of Adipo offers a novel therapeutic strategy for type 1 and type 2 diabetes.
