Impact of lack of suppression of glucagon on glucose tolerance in humans
Impact of lack of suppression of glucagon on glucose tolerance in humans
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DOI：
10.1152/ajpendo.1999.277.2.e283
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发表时间：
1999-08-01
影响因子：
5.1
通讯作者：
Rizza, R
中科院分区：
文献类型：
--
作者：
Shah, P;Basu, A;Rizza, R
2 型糖尿病患者的 α 细胞和 β 细胞功能均存在缺陷。为了确定当胰岛素分泌受损时胰高血糖素抑制不足是否会导致高血糖，而当胰岛素分泌完好时则不会，对 20 名非糖尿病受试者进行了两次研究。在这两种情况下，“餐时”葡萄糖输注均持续 5 小时以上，同时抑制内源性激素分泌。输注胰岛素是为了模拟非糖尿病患者 (n = 10) 或糖尿病患者 (n = 10) 的餐后情况。胰高血糖素以 1.25 ng.kg(-1).min(-1) 的速率输注，从零时间开始输注以防止胰高血糖素下降（非抑制研究日），或从 2 小时开始输注以造成胰高血糖素短暂下降（抑制研究日）。在“糖尿病胰岛素谱”期间，缺乏胰高血糖素抑制导致峰值葡萄糖浓度（11.9 +/- 0.4 vs. 8.9 +/- 9.4 mmol/l）和葡萄糖基础上方面积（927 +/- 77 vs. 546 +/- 112 mmol.l(-1).6 h）显着增加（P < 0.002），因为胰岛素受损（P <相反，在“非糖尿病”胰岛素情况下，缺乏胰高血糖素抑制仅导致峰值葡萄糖浓度（9.1 +/- 0.4 vs. 8.4 +/- 0.3 mmol/l）和葡萄糖基础上方面积（654 +/- 146 vs. 488 +/- 118）略有增加（P < 0.02）。有趣的是，当胰高血糖素被抑制时，在非糖尿病和糖尿病胰岛素曲线期间葡萄糖浓度仅存在微小差异。这些数据表明，当胰岛素可用性有限时，缺乏胰高血糖素抑制可导致显着的高血糖，因此意味着胰高血糖素分泌和/或胰高血糖素作用的抑制剂可能是此类个体的有用治疗剂。
People with type 2 diabetes have defects in both alpha- and beta-cell function. To determine whether lack of suppression of glucagon causes hyperglycemia when insulin secretion is impaired but not when insulin secretion is intact, twenty nondiabetic subjects were studied on two occasions. On both occasions, a "prandial" glucose infusion was given over 5 h while endogenous hormone secretion was inhibited. Insulin was infused so as to mimic either a nondiabetic (n = 10) or diabetic (n = 10) postprandial profile. Glucagon was infused at a rate of 1.25 ng.kg(-1).min(-1), beginning either at time zero to prevent a fall in glucagon (nonsuppressed study day) or at 2 h to create a transient fall in glucagon (suppressed study day). During the "diabetic insulin profile, lack of glucagon suppression resulted in a marked increase (P < 0.002) in both the peak glucose concentration (11.9 +/- 0.4 vs. 8.9 +/- 9.4 mmol/l) and the area above basal of glucose (927 +/- 77 vs. 546 +/- 112 mmol.l(-1).6 h) because of impaired (P < 0.001) suppression of glucose production. In contrast, during the "nondiabetic" insulin profile, lack of suppression of glucagon resulted in only a slight increase (P < 0.02) in the peak glucose concentration (9.1 +/- 0.4 vs. 8.4 +/- 0.3 mmol/l) and the area above basal of glucose (654 +/- 146 vs. 488 +/- 118 mmol.l(-1).6 h). Of interest, when glucagon was suppressed, glucose concentrations differed only minimally during the nondiabetic and diabetic insulin profiles. These data indicate that lack of suppression of glucagon can cause substantial hyperglycemia when insulin availability is limited, therefore implying that inhibitors of glucagon secretion and/or glucagon action are likely to be useful therapeutic agents in such individuals.