Wajngot A, Roovete A, Vranić M, Luft R, Efendić S
Proc Natl Acad Sci U S A. 1982 Jul;79(14):4432-6. doi: 10.1073/pnas.79.14.4432.
In an attempt to determine the mechanism of decreased glucose tolerance in lean type 2 diabetics, glucose turnover in such subjects and controls was studied under basal conditions and during hyperglycemia induced by intravenous administration of glucose. The diabetics had decreased intravenous glucose tolerance and a fasting plasma glucose of 6-8 mM (108-144 mg/dl). Glucose was infused for 2 hr at 2 mg/kg per min in the controls (n = 16) and diabetics (n = 9). Furthermore, 11 healthy subjects were infused also with glucose at 4 mg/kg per min to match the glycemia of the diabetics. Glucose production, utilization, and metabolic clearance were assessed by the primed constant tracer infusion technique. In the basal state, diabetics showed normal plasma insulin, C peptide, and glucagon concentrations. Their increased basal plasma glucose levels were associated with normal rates of glucose production and utilization, but the metabolic glucose clearance was 21% lower than in the controls (P < 0.001), indicating decreased sensitivity to insulin. During infusion of glucose at 2 mg/kg per min, the hyperglycemia attained in the diabetics (170 mg/dl) was higher than that in controls (115 mg/dl) but comparable to that of the controls exposed to the higher glucose load. With the lower glucose load, metabolic clearance rate decreased more markedly in diabetics, again suggesting insulin resistance. This was further substantiated by the fact that, at the same insulin levels, glucose utilization did not increase more in the diabetics than in the controls, although the glycemia reached was considerably higher in the diabetics. With the lower glucose load, glucose production was suppressed to the same degree in the controls and diabetics, although the attained glycemia was much more marked in the latter. Because both insulin and hyperglycemia can suppress glucose production, some defect in the regulation of glucose production of the diabetics is also indicated. The insulin and C peptide levels were much higher in the controls than in the diabetics at the same levels of glycemia, demonstrating the inadequacy of insulin response to glycemia of the diabetics. Glucagon concentration was equally suppressed in all groups. In conclusion, impaired glucose tolerance of mild type 2 diabetics resulted both from inadequate insulin response and from decreased sensitivity to insulin. The insulin resistance could mainly be ascribed to inadequate glucose uptake, but a defect in glucose-induced suppression of glucose production may also have contributed.
为了确定瘦型2型糖尿病患者糖耐量降低的机制，我们研究了此类患者及对照组在基础状态下以及静脉注射葡萄糖诱导的高血糖期间的葡萄糖周转率。糖尿病患者的静脉葡萄糖耐量降低，空腹血糖为6 - 8 mM（108 - 144 mg/dl）。在对照组（n = 16）和糖尿病患者（n = 9）中，以2 mg/kg每分钟的速度输注葡萄糖2小时。此外，对11名健康受试者以4 mg/kg每分钟的速度输注葡萄糖，使其血糖水平与糖尿病患者匹配。通过单次静脉注射恒定示踪剂输注技术评估葡萄糖生成、利用和代谢清除率。在基础状态下，糖尿病患者的血浆胰岛素、C肽和胰高血糖素浓度正常。他们升高的基础血浆葡萄糖水平与正常的葡萄糖生成和利用率相关，但代谢性葡萄糖清除率比对照组低21%（P < 0.001），表明对胰岛素的敏感性降低。在以2 mg/kg每分钟的速度输注葡萄糖期间，糖尿病患者达到的高血糖水平（170 mg/dl）高于对照组（115 mg/dl），但与接受更高葡萄糖负荷的对照组相当。在较低的葡萄糖负荷下，糖尿病患者的代谢清除率下降更为明显，再次提示胰岛素抵抗。这进一步得到证实，即在相同胰岛素水平下，糖尿病患者的葡萄糖利用率增加幅度并不比对照组大，尽管糖尿病患者达到的血糖水平要高得多。在较低的葡萄糖负荷下，对照组和糖尿病患者的葡萄糖生成受到同等程度的抑制，尽管后者达到的血糖水平更为显著。由于胰岛素和高血糖都能抑制葡萄糖生成，这也表明糖尿病患者在葡萄糖生成调节方面存在一些缺陷。在相同血糖水平下，对照组的胰岛素和C肽水平比糖尿病患者高得多，表明糖尿病患者对血糖的胰岛素反应不足。所有组的胰高血糖素浓度均受到同等程度的抑制。总之，轻度2型糖尿病患者的糖耐量受损既源于胰岛素反应不足，也源于对胰岛素的敏感性降低。胰岛素抵抗主要归因于葡萄糖摄取不足，但葡萄糖诱导的葡萄糖生成抑制缺陷也可能起到了一定作用。
