Shah P, Basu A, Basu R, Rizza R
Endocrine Research Unit, Mayo Clinic, Rochester, Minnesota 55905, USA.
Am J Physiol. 1999 Aug;277(2):E283-90. doi: 10.1152/ajpendo.1999.277.2.E283.
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 +/- 0.4 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.
2型糖尿病患者的α细胞和β细胞功能均存在缺陷。为了确定在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，而在胰岛素分泌正常时则不会，对20名非糖尿病受试者进行了两次研究。在这两次研究中，在抑制内源性激素分泌的同时，进行了5小时的“餐时”葡萄糖输注。输注胰岛素以模拟非糖尿病（n = 10）或糖尿病（n = 10）餐后状态。以1.25 ng·kg⁻¹·min⁻¹的速率输注胰高血糖素，要么在零时开始以防止胰高血糖素下降（非抑制研究日），要么在2小时时开始以造成胰高血糖素短暂下降（抑制研究日）。在“糖尿病”胰岛素状态下，由于葡萄糖生成抑制受损（P < 0.001），胰高血糖素抑制不足导致峰值血糖浓度（11.9±0.4 vs. 8.9±0.4 mmol/L）和基础血糖以上面积（927±77 vs. 546±112 mmol·L⁻¹·6 h）均显著增加（P < 0.002）。相比之下，在“非糖尿病”胰岛素状态下，胰高血糖素抑制不足仅导致峰值血糖浓度（9.1±0.4 vs. 8.4±0.3 mmol/L）和基础血糖以上面积（654±146 vs. 488±118 mmol·L⁻¹·6 h）略有增加（P < 0.02）。有趣的是，当胰高血糖素被抑制时，非糖尿病和糖尿病胰岛素状态下的血糖浓度差异仅微乎其微。这些数据表明，当胰岛素可用性有限时，胰高血糖素抑制不足可导致显著的高血糖，因此意味着胰高血糖素分泌抑制剂和/或胰高血糖素作用抑制剂可能是这类患者有用的治疗药物。
