title: Potentiating effect of metformin on insulin-induced glucose uptake and glycogen metabolism with Xenopus oocytes.
abstract: Xenopus laevis oocytes were chosen as the in vitro model for this study with the aim of reconsidering metformin action on the main insulin-responsive glucose pathway. Metformin alone, when present at a therapeutic dose (20 micromol/l) in the incubation medium, did not alter the basal rate of glucose uptake or of glycogen synthesis as measured by [U-14C] D-glucose incorporation. The drug had no effect on the main rate-limiting enzyme implicated in this pathway, i.e. glycogen synthase. In contrast, when combined with 2 micromol/l insulin, metformin led to a specific rise of both free and stored glucose, by 42.4 and 102.3% respectively. Moreover, a short-term preincubation of mature oocytes with metformin, but in the absence of glucose, enhanced significantly the amount of synthase a when stimulated by 50 nmol/l insulin (basal 17.4 +/- 5.7%, metformin 21.3 +/- 4.1%, insulin 31.2 +/- 4.6%, metformin together with insulin 62.7 +/- 4.2%, p < 0.005, n = 5). Interestingly, the microinjection of this biguanide, at a final concentration of 20 nmol/l, allowed a similar biochemical response. These data clearly suggest that metformin could act primarily at postreceptor steps which are thought to be key sites in controlling the cellular glucose homeostasis.
authors.affiliation: Laboratory of Comparative Biochemistry and Physiology, Facultés Universitaires Notre-Dame de la Paix, Namur, Belgium.
authors.forename: D
authors.initials: D
authors.lastname: Detaille
authors.forename: N
authors.initials: N
authors.lastname: Wiernsperger
authors.forename: P
authors.initials: P
authors.lastname: Devos
mesh_terms: D019325:3-O-Methylglucose / Q000378:metabolism; D000818:Animals; D004357:Drug Synergism; D005260:Female; D005947:Glucose / Q000378:metabolism*; D006003:Glycogen / Q000096:biosynthesis*; D006006:Glycogen Synthase / Q000378:metabolism; D066298:In Vitro Techniques; D007328:Insulin / Q000494:pharmacology*; D007700:Kinetics; D008687:Metformin / Q000494:pharmacology*; D009865:Oocytes / Q000187:drug effects / Q000378:metabolism*; D014982:Xenopus laevis
chemical_list: D007328:Insulin; D019325:3-O-Methylglucose; D006003:Glycogen; D008687:Metformin; D006006:Glycogen Synthase; D005947:Glucose