Piccinini M, Rabbone I, Novi R F, Alberto G, Mostert M, Musso A, Vai S, Gamba S, Rinaudo M T
Department of Experimental Medicine and Oncology, Section of Biochemistry, University of Turin, Turin, Italy.
Int J Obes Relat Metab Disord. 2000 Jun;24(6):735-41. doi: 10.1038/sj.ijo.0801212.
Circulating lymphocytes of obese individuals with and without type 2 diabetes have derangements of pyruvate dehydrogenase (PDH) that are described as reflecting a disorder underlying systemic insulin resistance, namely basal activity below normal and, in vitro, unresponsiveness to insulin at 33 pmol/l and activation at 330 pmol/l instead of activation and inhibition as in controls.
To explore whether the above enzyme derangements are overcome in obese individuals on dexfenfluramine treatment, known to improve poor peripheral insulin sensitivity.
Fifteen obese diabetic patients and 15 age-matched euglycaemic obese subjects with normal glucose tolerance were enrolled for a trial composed of two 21-day periods; in the first (D-21-D0), participants received a placebo, and in the second (D0-D21), dexfenfluramine (30 mg/day). At D-21, D0 and D21 participants were evaluated for weight, BMI, fasting glycaemia (FG), fasting insulinaemia (FI), fasting insulin resistance index (FIRI), area under the glycaemic (G-AUC) and insulinaemic (I-AUC) curves from an OGT test, and for PDH activity assayed in their circulating lymphocytes before (basal activity) and after incubation with 33 or 330 pmol/l insulin. At D2, basal PDH activity and clinical parameters were assayed.
In both groups of participants at D0 all parameters tested were constant with respect to D-21; at D2, only basal PDH activity rose significantly; at D21, basal and insulin stimulated PDH activities were normalized and weight decreased significantly, as did FG, FI, FIRI and G-AUC in the diabetic, and FI, FIRI, G-AUC and I-AUC in the non-diabetic participants.
In obese, non-diabetic and diabetic individuals on dexfenfluramine treatment, amelioration of clinical parameters and indexes of poor insulin sensitivity of blood glucose homeostasis are preceded by correction, in their circulating lymphocytes, of PDH derangements described as reflecting a disorder underlying insulin resistance.
患有和未患2型糖尿病的肥胖个体的循环淋巴细胞存在丙酮酸脱氢酶（PDH）紊乱，这种紊乱被认为反映了全身性胰岛素抵抗的潜在病症，即基础活性低于正常水平，并且在体外，对33 pmol/l胰岛素无反应，而对330 pmol/l胰岛素有激活反应，而不像对照组那样有激活和抑制反应。
探讨在已知能改善外周胰岛素敏感性差的右芬氟拉明治疗的肥胖个体中，上述酶紊乱是否得到纠正。
招募15名肥胖糖尿病患者和15名年龄匹配、糖耐量正常的血糖正常肥胖受试者进行一项试验，该试验由两个21天周期组成；在第一个周期（D - 21至D0），参与者接受安慰剂，在第二个周期（D0至D21），接受右芬氟拉明（30毫克/天）。在D - 21、D0和D21时，评估参与者的体重、体重指数、空腹血糖（FG）、空腹胰岛素血症（FI）、空腹胰岛素抵抗指数（FIRI）、口服葡萄糖耐量试验（OGT）的血糖曲线下面积（G - AUC）和胰岛素曲线下面积（I - AUC），以及在其循环淋巴细胞中在与33或330 pmol/l胰岛素孵育之前（基础活性）和之后测定的PDH活性。在D2时，测定基础PDH活性和临床参数。
在D0时，两组参与者的所有测试参数相对于D - 21均保持不变；在D2时，仅基础PDH活性显著升高；在D21时，基础和胰岛素刺激的PDH活性恢复正常，体重显著下降，糖尿病患者的FG、FI、FIRI和G - AUC以及非糖尿病参与者的FI、FIRI、G - AUC和I - AUC也显著下降。
在接受右芬氟拉明治疗的肥胖、非糖尿病和糖尿病个体中，血糖稳态胰岛素敏感性差的临床参数和指标得到改善之前，其循环淋巴细胞中被描述为反映胰岛素抵抗潜在病症的PDH紊乱先得到纠正。
