Doxycycline in Extremely Low Dose Improves Glycemic Control and Islet Morphology in Mice Fed a High-Fat Diet

极低剂量的强力霉素可改善高脂饮食小鼠的血糖控制和胰岛形态

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作者:Yixin Chen, Yu Chen, Na Wang, Shanhong Gu, Meilin Wang, Yucai Fu, Chiju Wei, Wencan Xu

Conclusion

Our results suggest that doxycycline, even at an extremely low dose, could improve glycemic control and islet morphology via its anti-inflammatory activities.

Methods

C57BL/6J mice were fed with a high-fat diet to induce diabetic and obese conditions. Three sub-antimicrobial dosages of doxycycline (200, 20, and 2 μg/mL) were added to drinking water for 23 weeks during the housing phase.

Purpose

Chronic low-grade inflammation is detected in obese and diabetic individuals. Tetracyclines, used as antibiotics for years, have been demonstrated to have diverse non-bactericidal effects, including anti-tumor and anti-inflammatory activities. This study aimed to investigate whether doxycycline at sub-antimicrobial concentrations could improve glycemic control in mice fed a high-fat diet, through its anti-inflammatory activities.

Results

Doxycycline at 200 μg/mL tended to increase body weight, islet mass, and the percentage of large islets (diameter >350 μm). At 20 μg/mL, doxycycline significantly improved glucose tolerance and decreased fasting blood glucose. At 2 μg/mL, doxycycline increased the percentage of small islets (diameter <80 μm). Serum C-reactive protein and lipopolysaccharide levels significantly decreased while the beta-cell ratio increased in all doxycycline-administered mice.

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