| Project/Area Number |
15390294
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (B)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Endocrinology
|
|---|
| Research Institution | Tokyo Medical and Dental University |
|---|
Principal Investigator |
OGAWA Yoshihiro Tokyo Medical and Dental University, Medical Research Institute, Professor, 難治疾患研究所, 教授 (70291424)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
SUGANAMI Takayoshi Tokyo Medical and Dental University, Medical Research Institute, Assistant Professor, 難治疾患研究所, 助手 (50343752)
|
|---|
| Project Period (FY) |
2003 – 2004
|
| Project Status |
Completed (Fiscal Year 2004)
|
| Budget Amount *help |
¥14,600,000 (Direct Cost: ¥14,600,000)
Fiscal Year 2004: ¥6,200,000 (Direct Cost: ¥6,200,000)
Fiscal Year 2003: ¥8,400,000 (Direct Cost: ¥8,400,000)
|
|---|
| Keywords | Leptin / Insulin / Insulin-deficient diabetes / Transgenic mice / Adiponectin / Atherosclerosis / Retinal neovascularization / レプチン抵抗性 / ob / obマウス / 虚血性網膜血管新生 / ストレプトゾトシン / 抗糖尿病薬 |
|---|
| Research Abstract |
Leptin is an important adipocytokine that acts directly on the hypothalamus, thereby regulating food intake and energy expenditure. Because leptin receptor is expressed not only in the hypothalamus but in a variety of peripheral tissues and leptin is capable of activating the JAK/STAT signaling pathway, suggesting that leptin works as a proinflammatory cytokine in peripheral target tissues.
1)Leptin as an antidiabetic agent in insulin-deficient diabetes : We showed that after streptozotocin injection, both transgenic skinny mice overexpressing leptin and their non-transgenic littermates developed marked hyperglycemia as a result of severe hypoinsulinemia (termed diabetic TGM and diabetic WT, respectively). Diabetic TGM became normoglycemic, when treated with insulin at such doses that did not improve hyperglycemia in diabetic WT. This study suggests that leptin can be used as an adjunct of insulin therapy in insulin-deficient diabetes, thereby providing an insight into the therapeutic implication of leptin as an anti-diabetic agent.
2)Pathonhvsioloizic role of leptin in ischemia-induced retinal neovascularization : Using the mouse retinopathy of prematurity model, we showed that leptin stimulates ischemia-induced retinal neovascularization possibly through the upregulation of endothelial VEGF. These observations suggest that leptin antagonism may offer a novel therapeutic strategy to prevent or treat diabetic retinopathy.
3)Diagnostic role of leptin in as a biomarker of atherosclerosis : Given that leptin and adiponectin are important mediators linking adiposity and atherosclerosis in the adipovascular axis, we demonstrated that leptin/adiponectin ratio is strongly correlated with pulse-wave velocity, a direct measure of arterial stiffness. We, therefore, postulate that the ratio may serve as a potential atherogenic index in obese type 2 diabetic patients.
|
