在胰岛素依赖型和非胰岛素依赖型糖尿病年轻患者中，细胞内钙增加，且佛波醇二丁酸酯与完整血小板的结合发生改变。

Increased intracellular calcium and altered phorbol dibutyrate binding to intact platelets in young subjects with insulin-dependent and non-insulin-dependent diabetes mellitus.

作者信息

Takaya J, Iwamoto Y, Higashino H, Ishihara R, Kobayashi Y

机构信息

Department of Pediatrics, Kansai Medical University, Osaka, Japan.

出版信息

Metabolism. 1997 Aug;46(8):949-53. doi: 10.1016/s0026-0495(97)90085-8.

DOI:10.1016/s0026-0495(97)90085-8

PMID:9258280

Abstract

Intracellular calcium ([Ca2+]i) and phorbol ester binding were studied in intact platelets of young patients with insulin-dependent (IDDM) and non-insulin-dependent (NIDDM) diabetes mellitus. Our objective was to evaluate disturbances in calcium regulation and signal transduction in platelets of diabetics. [Ca2+]i in platelets of the IDDM group (135 +/- 20 nmol/L) under basal conditions was significantly higher than that of the control group (81 +/- 8 nmol/L, P = .019), whereas at 60 seconds after stimulation with 0.1 National Institutes of Health (NIH) U/mL thrombin, [Ca2+]i in the NIDDM group (484 +/- 36 nmol/L) was significantly higher than that of the controls (347 +/- 22 nmol/L, P = .003) and IDDM group (360 +/- 45 nmol/L, P = .04), respectively. Phorbol 12,13-dibutyrate (PdBu) maximal binding capacity (Bmax) in the IDDM group was significantly lower than that in the control group either under basal conditions or after stimulation with thrombin (P = .0034 and P = .015, respectively). Bmax in the NIDDM group was significantly lower than that in the controls only after stimulation with thrombin (P = .047). The Kd for PdBu of the IDDM group was lower than that of the control group under basal conditions (P = .017). When analyzing the pooled data of all subjects, a significant correlation was observed between Bmax and Kd (under basal conditions, r = .544, P < .0001; after stimulation, r = .601, P < .0001). Our results support the idea that the increased affinity for PdBu may compensate for the decreased binding capacity. We interpret the data as indicating that the change in the binding of phorbol ester to protein kinase C (PKC) units may result in an altered PKC/calcium interaction in the pathogenesis of diabetes mellitus. Our study indicates that such metabolic derangements of [Ca2+]i have already been developing in young diabetic patients.

摘要

在胰岛素依赖型（IDDM）和非胰岛素依赖型（NIDDM）糖尿病年轻患者的完整血小板中，研究了细胞内钙浓度（[Ca2+]i）和佛波酯结合情况。我们的目的是评估糖尿病患者血小板中钙调节和信号转导的紊乱情况。IDDM组血小板在基础状态下的[Ca2+]i（135±20 nmol/L）显著高于对照组（81±8 nmol/L，P = 0.019），而在用0.1美国国立卫生研究院（NIH）单位/毫升凝血酶刺激60秒后，NIDDM组的[Ca2+]i（484±36 nmol/L）分别显著高于对照组（347±22 nmol/L，P = 0.003）和IDDM组（360±45 nmol/L，P = 0.04）。在基础状态下或用凝血酶刺激后，IDDM组佛波醇12,13 - 二丁酸酯（PdBu）的最大结合容量（Bmax）均显著低于对照组（分别为P = 0.0034和P = 0.015）。仅在凝血酶刺激后，NIDDM组的Bmax显著低于对照组（P = 0.047）。IDDM组在基础状态下PdBu的解离常数（Kd）低于对照组（P = 0.017）。在分析所有受试者的汇总数据时，观察到Bmax与Kd之间存在显著相关性（基础状态下，r = 0.544，P < 0.0001；刺激后，r = 0.601，P < 0.0001）。我们的结果支持这样一种观点，即对PdBu亲和力的增加可能补偿结合容量的降低。我们将这些数据解释为表明佛波酯与蛋白激酶C（PKC）单位结合的变化可能在糖尿病发病机制中导致PKC/钙相互作用改变。我们的研究表明，这种[Ca2+]i的代谢紊乱在年轻糖尿病患者中已经在发展。