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.
ABSTRACT
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.