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Glucagon‐like peptide‐1 and glucose‐dependent insulinotropic peptide: effects alone and in combination on insulin secretion and glucose disappearance in mice

机译:胰高血糖素样肽1和葡萄糖依赖性促胰岛素肽:单独或组合对小鼠胰岛素分泌和葡萄糖消失的作用

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摘要

Glucagon‐like peptide‐1 (GLP‐1) and glucose‐dependent insulinotropic peptide (GIP) stimulate insulin secretion. They are both released after meal ingestion, and therefore they might cooperate in their actions. However, whether there is a cooperative action of the two incretins is not known. This study therefore investigated the effects on insulin secretion and glucose disappearance of GLP‐1 and GIP when given together with intravenous glucose both alone and in combination in mice. Four different doses were used (0.003, 0.03, 0.3 and 3.0 nmol/kg), which ranged from subthreshold to maximal doses to stimulate first‐phase insulin secretion as evident from initial dose–response studies. It was found that at 0.03 nmol/kg and higher doses, glucose‐stimulated insulin secretion was augmented by both incretins. When they were given in combination, no further increase was observed, indicating no synergistic effect. Also, glucose disappearance rate was increased by 0.03 and 3.0 nmol/kg of the two incretins, both when they were given alone and in combination with, again, no synergy. Finally, glucose effectiveness (an index of noninsulin‐mediated processes) was enhanced by the two incretins, in particular GIP. We also found that insulin‐dependent and insulin‐independent mechanisms contributed 38% and 62%, respectively, to glucose tolerance after glucose alone; with GIP, the contribution by noninsulin‐dependent processes was remarkably dominant and with GLP‐1, insulin‐dependent processes were prevailing. In conclusion, GIP and GLP‐1 stimulate insulin secretion and glucose effectiveness in mice with no synergistic action, but with a dissociated contributory effector on glucose disposal: with GLP‐1 being more active on insulin‐dependent processes and GIP more active on noninsulin‐dependent processes.
机译:胰高血糖素样肽-1(GLP-1)和葡萄糖依赖性促胰岛素肽(GIP)刺激胰岛素分泌。他们都在进餐后被释放,因此他们可能会配合行动。但是,尚不清楚两个肠降血糖素是否有协同作用。因此,本研究调查了在小鼠中单独或联合静脉给予葡萄糖时,对GLP-1和GIP胰岛素分泌和葡萄糖消失的影响。从初始剂量反应研究可以明显看出,使用了四种不同的剂量(0.003、0.03、0.3和3.0 nmol / kg),从亚阈值到最大剂量范围来刺激胰岛素的第一阶段分泌。发现在0.03 nmol / kg和更高剂量下,两种肠降血糖素均可增加葡萄糖刺激的胰岛素分泌。当它们组合给予时,没有观察到进一步的增加,表明没有协同作用。同样,两种肠降血糖素的葡萄糖消失率分别增加0.03和3.0 nmol / kg,既可以单独使用也可以不协同使用。最后,两个肠降血糖素,特别是GIP增强了葡萄糖有效性(非胰岛素介导的过程的指标)。我们还发现,仅依赖葡萄糖后,依赖胰岛素​​和不依赖胰岛素​​的机​​制分别对葡萄糖耐量贡献了38%和62%。对于GIP,非胰岛素依赖过程的贡献显着,而对于GLP-1,胰岛素依赖过程占主导。总而言之,GIP和GLP-1刺激小鼠无协同作用,但对葡萄糖处理的贡献却不相关:GLP-1在依赖胰岛素​​的过程中更活跃,而GIP在非胰岛素治疗中更活跃。依赖的过程。

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