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2-Methoxyestradiol ameliorates glucose tolerance with the increase in β-cell mass in db/db mice
Takashi Yorifuji1, Toyoyoshi Uchida2, Hiroko Abe2
1Departments of Obstetrics and Gynecology.
Unlabelled:
Aims/Introduction: 2-Methoxyestradiol (2ME) is an estradiol metabolite with little estrogenic activity. Previous data identified its anti-carcinogenic properties and possible cardiovascular benefits. However, its effect on diabetes mellitus has not been fully elucidated. The aim of the present study was to determine the effects of 2ME on glucose metabolism in the diabetic state.
Materials And Methods:
To evaluate the effects of 2ME, pellets of two different doses of the drug were implanted into female db/db mice at the age of 5 weeks. Intraperitoneal glucose tolerance test and insulin tolerance test were carried out at the age of 8 weeks. The pancreas was harvested for morphological analysis and β-cell function at the age of 9 weeks.
Results:
2ME improved random blood glucose levels and glucose tolerance with increases in insulin levels during an intraperitoneal glucose tolerance test. Insulin sensitivity judged by an insulin tolerance test was comparable in the low- and high-dose 2ME groups and the control group. Although glucose-stimulated insulin secretion in isolated islets was comparable among the three groups, β-cell mass in 2ME-treated groups was higher than the control group. In the 2ME-treated groups, the number of Ki67-positive cells in islets was higher, whereas the number of cleaved caspase-3-positive cells was comparable with the control.
Conclusions:
2ME ameliorates glucose tolerance by promoting the proliferation of β-cell mass in db/db mice. Our data suggests its potential clinical usefulness as a disease-modifying drug for type 2 diabetes mellitus. (J Diabetes Invest, doi: 10.1111/j.2040-1124.2010.00087.x, 2011).
Insights
2-Methoxyestradiol (2ME) treatment improved glucose tolerance and blood glucose levels in diabetic mice. This suggests 2ME may be a potential therapeutic for type 2 diabetes by increasing beta-cell proliferation.
Area of Science:
- Endocrinology
- Metabolic Research
- Pharmacology
Background:
- 2-Methoxyestradiol (2ME), an estradiol metabolite, has demonstrated anti-carcinogenic and potential cardiovascular benefits.
- Its specific impact on glucose metabolism and diabetes mellitus remains largely uninvestigated.
Purpose of the Study:
- To investigate the effects of 2-Methoxyestradiol (2ME) on glucose metabolism in a diabetic mouse model.
- To determine if 2ME can ameliorate hyperglycemia and improve glucose tolerance in the context of diabetes.
Main Methods:
- Female db/db mice received 2ME via pellet implantation at 5 weeks of age.
- Glucose tolerance and insulin sensitivity were assessed using intraperitoneal glucose tolerance tests and insulin tolerance tests.
- Pancreatic tissue was analyzed for morphology and beta-cell function, including proliferation and apoptosis markers.
Main Results:
- 2ME administration led to improved random blood glucose levels and enhanced glucose tolerance.
- Insulin levels increased during glucose challenge, while insulin sensitivity remained comparable across groups.
- Beta-cell mass significantly increased in 2ME-treated mice, with higher Ki67 (proliferation) and similar cleaved caspase-3 (apoptosis) staining.
Conclusions:
- 2-Methoxyestradiol (2ME) improves glucose tolerance in diabetic mice by promoting beta-cell proliferation and increasing beta-cell mass.
- These findings highlight the potential of 2ME as a disease-modifying therapeutic agent for type 2 diabetes mellitus.