Metformin potentiates B-cell response to high glucose: an in vitro study on isolated perfused pancreas from normal rats.
This study investigated the effects of metformin on pancreatic A-B- and D-cell functions using the isolated perfused rat pancreas model. The lactate output rate following metformin infusion was also monitored. Metformin was infused at the low "therapeutic" concentration of 1.5 micrograms/ml and its effects were evaluated in three different glycaemic conditions: during a basal infusion of 4.44 mM glucose, during a moderate increase to 8.88 mM of glucose concentration, and finally during a higher 16.66 mM glycaemic stimulus. Basal insulin secretion and B-cell release during the lower hyperglycaemic stimulus were unaffected by metformin infusion. On the contrary, the drug significantly enhanced insulin response to 16.66 mM glucose, particularly by increasing the second phase of hormone release. Glucagon and somatostatin releases during metformin infusion were similar to the secretory pattern observed in the control experiments both in the basal condition and in the presence of the two different hyperglycaemic stimuli. Finally metformin did not modify the lactate output rate from perfused pancreas, irrespective of the different glycaemic conditions employed. Therefore our data suggest--at least in rats, in in vitro experiments but above all in the presence of markedly elevated hyperglycaemic conditions--that metformin may influence the glucose stimulatory effect on B-cell activity.