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Circulating palmitoleic acid is an independent determinant of insulin sensitivity, beta cell function and glucose tolerance in non-diabetic individuals: a longitudinal analysis.
Diabetologia ( IF 8.2 ) Pub Date : 2019-11-01 , DOI: 10.1007/s00125-019-05013-6
Domenico Tricò 1, 2 , Alessandro Mengozzi 1 , Lorenzo Nesti 1 , Mensud Hatunic 3 , Rafael Gabriel Sanchez 4 , Thomas Konrad 5 , Katarina Lalić 6 , Nebojša M Lalić 6 , Andrea Mari 7 , Andrea Natali 1 ,
Affiliation  

AIMS/HYPOTHESIS Experimental studies suggest that the fatty acid palmitoleate may act as an adipocyte-derived lipid hormone (or 'lipokine') to regulate systemic metabolism. We investigated the relationship of circulating palmitoleate with insulin sensitivity, beta cell function and glucose tolerance in humans. METHODS Plasma NEFA concentration and composition were determined in non-diabetic individuals from the Relationship between Insulin Sensitivity and Cardiovascular disease (RISC) study cohort at baseline (n = 1234) and after a 3 year follow-up (n = 924). Glucose tolerance, insulin secretion and beta cell function were assessed during an OGTT. Whole-body insulin sensitivity was measured by a hyperinsulinaemic-euglycaemic clamp (M/I) and OGTT (oral glucose insulin sensitivity index [OGIS]). The liver insulin resistance index was calculated using clinical and biochemical data. Body composition including fat mass was determined by bioelectrical impedance. RESULTS Circulating palmitoleate was proportional to fat mass (r = 0.21, p < 0.0001) and total NEFA levels (r = 0.19, p < 0.0001). It correlated with whole-body insulin sensitivity (M/I: standardised regression coefficient [std. β] = 0.16, p < 0.0001), liver insulin resistance (std. β = -0.14, p < 0.0001), beta cell function (potentiation: std. β = 0.08, p = 0.045) and glucose tolerance (2 h glucose: std. β = -0.24, p < 0.0001) after adjustment for age, sex, BMI, adiposity and other NEFA. High palmitoleate concentrations prevented the decrease in insulin sensitivity associated with excess palmitate (p = 0.0001). In a longitudinal analysis, a positive independent relationship was observed between changes in palmitoleate and insulin sensitivity over time (std. β = 0.07, p = 0.04). CONCLUSIONS/INTERPRETATION We demonstrated that plasma palmitoleate is an independent determinant of insulin sensitivity, beta cell function and glucose tolerance in non-diabetic individuals. These results support the role of palmitoleate as a beneficial lipokine released by adipose tissue to prevent the negative effects of adiposity and excess NEFA on systemic glucose metabolism.

中文翻译:

循环棕榈油酸是非糖尿病患者胰岛素敏感性,β细胞功能和葡萄糖耐量的独立决定因素:一项纵向分析。

目的/假设实验研究表明,脂肪酸棕榈油酸酯可能起脂肪细胞源性脂质激素(或“脂因子”)的作用,以调节全身代谢。我们调查了人类中循环棕榈酸酯与胰岛素敏感性,β细胞功能和葡萄糖耐量的关系。方法根据基线(n = 1234)和3年随访(n = 924)后胰岛素敏感性与心血管疾病(RISC)研究队列之间的关系确定非糖尿病个体的血浆NEFA浓度和组成。在OGTT期间评估了葡萄糖耐量,胰岛素分泌和β细胞功能。全身胰岛素敏感性通过高胰岛素血症-正常血糖钳(M / I)和OGTT(口服葡萄糖胰岛素敏感性指数[OGIS])进行测量。使用临床和生化数据计算肝脏胰岛素抵抗指数。通过生物电阻抗确定包括脂肪量在内的身体组成。结果循环的棕榈油酸酯与脂肪量(r = 0.21,p <0.0001)和总NEFA水平(r = 0.19,p <0.0001)成正比。它与全身胰岛素敏感性(M / I:标准化回归系数[std。β] = 0.16,p <0.0001),肝胰岛素抵抗(标准β= -0.14,p <0.0001),β细胞功能(增强)相关。 :调整了年龄,性别,BMI,肥胖症和其他NEFA后,标准β= 0.08,p = 0.045)和葡萄糖耐量(2小时葡萄糖:标准β= -0.24,p <0.0001)。高棕榈酸酯浓度可防止与过量棕榈酸酯相关的胰岛素敏感性降低(p = 0.0001)。在纵向分析中,随着时间的推移,棕榈油酸酯的变化与胰岛素敏感性之间存在正独立的关系(标准β= 0.07,p = 0.04)。结论/解释我们证明血浆棕榈油酸酯是非糖尿病个体中胰岛素敏感性,β细胞功能和葡萄糖耐量的独立决定因素。这些结果支持了棕榈油酸酯作为脂肪组织释放的有益脂因子的作用,以防止肥胖症和过多的NEFA对全身葡萄糖代谢的负面影响。
更新日期:2019-11-01
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