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To study the mechanism(s) of action of metformin, fragments of human subcutaneous adipose tissue were incubated with therapeutic blood concentrations of metformin. In the absence of insulin no effect of metformin was seen on either lipolysis or glucose metabolism. When insulin was present, however, metformin stimulated glucose conversion into both triglycerides and CO2. In marked contrast, no effect of metformin was observed on the antilipolytic effect of insulin. In agreement with this selective effect no change in insulin binding was found. In conclusion, metformin seems to exert its effect on glucose metabolism by potentiating the action of insulin at a post-receptor level, possibly on the rate of glucose transport.
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