Metformin enhances insulin binding to "in vitro" down regulated human fat cells

Insulin binding to human adipose tissue from surgical patients was determined after three different preincubation conditions: a) 24 hrs in the presence or absence of 80 ng/ml insulin; b) 24 hrs in the presence of 80 ng/ml insulin or insulin plus 4 micrograms/ml metformin; c) 48 hrs pre-incubation as in b). We found that insulin down regulated its own receptor after 24 hours pre-incubation; when metformin was present in the pre-incubation medium together with insulin, insulin binding to adipose tissue was significantly higher than in tissue exposed to insulin alone after 48 hrs pre-incubation; a similar effect of metformin was already seen after 24 hrs, but was not statistically significant. We suggest that metformin can correct down regulation of the insulin receptor. This finding could explain discrepant results among studies dealing with the influence of metformin on insulin binding. Moreover, these results could be useful in understanding the mechanism of action of metformin in insulin-resistant states, e.g. type II diabetes.