Program

PO1-5-16

Aminoguanigine improves increasing Blood glucose levels in ovx mice

[Speaker] Satoru Mitazaki:1
[Co-author] Mina Iide:1, Shigeyoshi Honma:2, Miwako Suto:3, Naho Kato:3, Naohito Kuroda:3, Kouichi Hiraiwa:4, Makoto Yoshida:2, Sumiko Abe:1
1:Lab. of Forensic Toxicol., Fac. Pharmacy, Takasaki Univ. Health and Welfare, Japan, 2:Dept. pathophysiol., Fac. Pharmacy, Takasaki Univ. Health and Welfare, Japan, 3:Dept. Legal Med., Fukushima Med. Univ., Japan, 4:Clinical Lab., Jusendou General Hospital, Japan

[Background]
 Estrogen is recognized as a key regulator of glucose homeostasis since estrogen deficiency promotes insulin resistance in menopausal women, resulting in an increased risk of type 2 diabetes. Estrogen is thought to control blood glucose levels by participating in activation of an insulin receptor. An ovariectomized (ovx) animal is a typical experimental model for investigation of postmenopausal pathologic changes due to estrogen deficiency in women. Using sham and ovx wild-type (WT) and inducible nitric oxide synthase knockout (iNOSKO) mice, we examined blood glucose levels to evaluate the role of estrogen and iNOS in progress of diabetes.
[Methods]
 Female WT C57BL/6J mice and iNOSKO mice in a C57BL/6 background weighing 15 to 20 g were used for the animal studies. An ovx or sham operation was performed at 8 weeks of age. Eight weeks after surgery blood glucose levels were measured. Aminoguanigine (AG), an iNOS inhibitor, and Olanzapine (OLZ), an antipsychotic, were freshly prepared in sterile saline. Mice were given either OLZ (5 mg/kg) or AG (100 mg/kg) intraperitoneally 30 min before oral glucose tolerance test (OGTT).
[Results]
 Significant increases of blood glucose levels during OGTT were observed in WT and iNOSKO mice 5 weeks after streptzotocin (STZ) administration. Interestingly, blood glucose levels were higher in WT mice than those in iNOSKO mice. AG reduced blood glucose levels that were increased by STZ administration. Significant increases of blood glucose levels during OGTT were observed in ovx mice compared to those in sham mice. In iNOSKO ovx mice, blood glucose levels during OGTT were rapidly reduced compared to those in WT ovx mice. OLZ significantly increased blood glucose levels in ovx mice but not in sham mice. AG pretreatment reduced blood glucose level in OLZ treated ovx mice to those in control mice.
[Conclusions]
 These results indicate that estrogen prevents progress of diabetes, whereas, iNOS promotes diabetes, and that estrogen somehow participates in iNOS activity.
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