Differential effects of metformin on smooth muscle contractile properties of duodenum, uterus and bladder

Abstract

The widely‐used antidiabetic agent metformin frequently causes gastrointestinal (GI) side effects. When taken orally, metformin reaches millimolar levels in GI tissues. Previously, we found that such levels exert contrasting effects on contractile properties of intact duodenal tissues isolated from male rats, i.e. inhibition of spontaneously‐occurring contractions and those induced by 5‐hydroxytryptamine (5HT) and high potassium (K) but enhancement of those induced by acetylcholine (ACh). In the present study, we found that the same levels of metformin exerted similar effects in duodenal tissues isolated from female rats but different effects in uterine and urinary bladder tissues from the same rats. In uterus, metformin inhibited K‐induced contractions but failed to meaningfully alter spontaneous contractions and those induced by 5HT and ACh. In bladder, metformin enhanced ACh‐induced contractions but failed to meaningfully alter spontaneous contractions and those induced by 5HT and K. Such a unique set of tissue specificities should greatly facilitate future efforts to unravel mechanisms responsible for metformin's various effects. Supported by Midwestern University.