Simsolo R B, Ong J M, Saffari B, Kern P A
Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA 90048.
J Lipid Res. 1992 Jan;33(1):89-95.
Patients with diabetes commonly manifest hypertriglyceridemia along with decreased adipose tissue lipoprotein lipase (LPL) activity, and improved diabetes control tends to reverse these abnormalities. To better understand the mechanism of regulation of LPL in diabetes, 11 diabetic patients (3 type I, 8 type II) were brought under improved glycemic control, and adipose tissue LPL gene expression was assessed by performing paired fat biopsies. Six of the 11 patients attained improved control with insulin, with a decrease in glycohemoglobin (glyc Hgb) from 13.8 +/- 0.9 to 10.4 +/- 0.6%; 5 patients attained improved control with glyburide (glyc Hgb fell from 14.2 +/- 2.4 to 8.8 +/- 0.6%), and together they demonstrated a lowering of serum triglycerides and total cholesterol. No changes were observed in HDL cholesterol. Improved diabetes control resulted in a significant increase in LPL activity in both the heparin-releasable (HR) and extractable (EXT) fractions of adipose tissue, as well as in LPL immunoreactive mass. The change in LPL activity with improved control was variable, and showed a positive correlation with the HDL levels prior to treatment (r = 0.74, P less than 0.02). When adipose tissue was pulse-labeled with [35S]methionine, there was an increase in isotope incorporation into LPL after treatment, indicating an increase in LPL synthetic rate. However, improved diabetes control resulted in no significant change in LPL mRNA levels. Thus, improved glycemic control resulted in an increase in LPL activity which correlated with each patient's basal high density lipoprotein. This increase in LPL activity was accompanied by an increase in LPL immunoreactive mass, and an increase in LPL synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)
糖尿病患者通常表现为高甘油三酯血症,同时脂肪组织脂蛋白脂肪酶(LPL)活性降低,而改善糖尿病控制往往会逆转这些异常情况。为了更好地理解糖尿病中LPL的调节机制,对11例糖尿病患者(3例I型,8例II型)进行了血糖控制改善,并通过成对的脂肪活检评估脂肪组织LPL基因表达。11例患者中有6例通过胰岛素实现了更好的控制,糖化血红蛋白(glyc Hgb)从13.8±0.9降至10.4±0.6%;5例患者通过格列本脲实现了更好的控制(glyc Hgb从14.2±2.4降至8.8±0.6%),他们共同表现出血清甘油三酯和总胆固醇降低。高密度脂蛋白胆固醇未观察到变化。改善糖尿病控制导致脂肪组织的肝素可释放(HR)和可提取(EXT)部分的LPL活性以及LPL免疫反应性物质显著增加。LPL活性随控制改善的变化是可变的,并且与治疗前的高密度脂蛋白水平呈正相关(r = 0.74,P小于0.02)。当用[35S]甲硫氨酸对脂肪组织进行脉冲标记时,治疗后LPL中同位素掺入增加,表明LPL合成速率增加。然而,改善糖尿病控制导致LPL mRNA水平无显著变化。因此,改善血糖控制导致LPL活性增加,这与每位患者的基础高密度脂蛋白相关。LPL活性的这种增加伴随着LPL免疫反应性物质的增加以及LPL合成的增加。(摘要截断于250字)