Regular Metformin Treatment In Obese Mice Although Appetite Improved But Not Glucose Tolerance

tareq 2019-05-25 13:50:12

Sameer Abu-Eid1,  Clemens Fürnsinn2,  Anton Luger3,   Thomas Scherer4.

1.     PhD Endocrinology nutrition and metabolism. European gaza hospital

2.     PhD, Associate Professor of Metabolic Physiology Division of Endocrinology and Metabolism, Department of Internal Medicine III, Medical University of Vienna.

3.     PhD, Head of the Clinical Division of Endocrinology and Metabolism at the MedUni Vienna.

4.     PhD, Division of Endocrinology and Metabolism, Department of Internal Medicine III, Medical University of Vienna.


Background: Although metformin the first choice drug for the treatment of type 2 diabetes, the precise mechanism of action remains controversial. Investigating the glucose lowering effect of metformin in rodents is highly inconsistence. Given the contradictories literature reports, we have carried out our own investigations.

Experiments and results: Two experiments were done, in the first one: The tests were carried out on male C57BL / 6J mice that exhibited obesity, insulin resistance, and glucose intolerance. Mice were treated daily for 7 weeks with an intraperitoneal injection (ip) of 50 mg/kg metformin, which is considered a low dose in rodents, and compared with vehicle-treated controls. The ip glucose tolerance test (1g/kg) that was carried out 24 h after the last Metformin injection showed only a non-significant trend to improved glucose homeostasis. The metformin, however, was associated with a reduction of food intake by 5-10% and reduced weight gain.

In the second experiment Mice were treated with high doses of metformin mixed in drinking water  (mean intake per day 300 mg / kg metformin). Herein the control mice were fed restrictedly to exclude the indirect Metformin effect on body weight.  In fact, the glucose tolerance significantly deteriorated for the same body weight mice after 6 weeks by Metformin. Then, the control animals were allowed to eat freely (F), which had an impact on glucose tolerance (no significant worsening of glucose tolerance by metformin was seen more.

Both in the metformin-treated and in control mice, greater weight gain is associated with poor glucose tolerance. In relation to weight gain, the glucose tolerance of the controls seemed even better than that of the metformin-treated mice. Compared to only those mice that were exhibited weight gain in a similar range, so could be even a significant negative effect of metformin on glucose tolerance seen.

Conclusion: Appetite inhibition by metformin in mice are much more pronounced than in humans and short-term lowering of blood glucose immediately after administration. A reduction in the blood glucose by regular intake, which is the clinical utility of metformin to reason, however, does not occur in obese mice.

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