Gregorio F, Filipponi P, Ambrosi F, Cristallini S, Marchetti P, Calafiore R, Navalesi R, Brunetti P
Istituti di Clinica Medica Ie, Università di Perugia, Italy.
Diabete Metab. 1989 May-Jun;15(3):111-7.
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.
本研究使用离体灌注大鼠胰腺模型，研究了二甲双胍对胰腺A、B和D细胞功能的影响。同时监测了二甲双胍输注后的乳酸输出率。以1.5微克/毫升的低“治疗”浓度输注二甲双胍，并在三种不同血糖条件下评估其效果：在基础输注4.44毫摩尔/升葡萄糖期间、在葡萄糖浓度适度增加至8.88毫摩尔/升期间以及最后在更高的16.66毫摩尔/升血糖刺激期间。基础胰岛素分泌以及较低血糖刺激期间的B细胞释放不受二甲双胍输注的影响。相反，该药物显著增强了对16.66毫摩尔/升葡萄糖的胰岛素反应，特别是通过增加激素释放的第二阶段。在基础条件以及存在两种不同血糖刺激的情况下，二甲双胍输注期间的胰高血糖素和生长抑素释放与对照实验中观察到的分泌模式相似。最后，无论采用何种不同血糖条件，二甲双胍均未改变灌注胰腺的乳酸输出率。因此，我们的数据表明——至少在大鼠中，在体外实验中，尤其是在明显升高的高血糖条件下——二甲双胍可能会影响葡萄糖对B细胞活性的刺激作用。
