Rocca A S, LaGreca J, Kalitsky J, Brubaker P L
Department of Physiology, University of Toronto, Toronto, Ontario, Canada.
Endocrinology. 2001 Mar;142(3):1148-55. doi: 10.1210/endo.142.3.8034.
Diets enriched in monounsaturated fatty acids (MUFA)s have been shown to benefit glycemic control. Furthermore, MUFAs specifically stimulate secretion of the antidiabetic hormone, Glucagon-like peptide-1 (GLP-1) in vitro. To determine whether the MUFA-induced benefit in glycemic tolerance in vivo is due to increased GLP-1 release, lean Zucker rats were pair-fed a synthetic diet containing 5% fat derived from either olive oil (OO; 74% MUFA) or coconut oil (CO; 87% saturated fatty acids; SFA) for 2 weeks. Food intake and body weight gain were similar for both groups over the feeding period. The OO group had improved glycemic tolerance compared with the CO group in both oral and duodenal glucose tolerance tests [area under curve (AUC) 121 +/- 61 vs. 290 +/- 24 mM.120 min, P < 0.05; and 112 +/- 28 vs. 266 +/- 65 mM.120 min, P < 0.05, respectively]. This was accompanied by increased secretion of gut glucagon-like immunoreactivity (gGLI; an index of GLP-1 levels) in the OO rats compared with the CO rats (402 +/- 96 vs. 229 +/- 33 pg/ml at t = 10 min, P < 0.05). Tissue levels of GLP-1 and plasma insulin and glucagon levels were not different between the two groups. To determine the total contribution of GLP-1 to the enhanced glycemic tolerance in OO rats, the GLP-1 receptor antagonist exendin(9-39) (Ex(9-39)) was infused 3 min before a duodenal glucose tolerance test. Ex(9-39) abolished the benefit in glycemic tolerance conferred by OO feeding (OO+Ex(9-39) vs. CO+Ex(9-39), P = NS), and resulted in a deterioration of glycemic tolerance in the OO+Ex(9-39) group when compared with the OO controls (AUC 331 +/- 21 vs. 112 +/- 28 mM.120 min, P < 0.05). To probe the mechanism by which the OO diet enhanced GLP-1 secretion, a GLP-1-secreting L cell line was incubated for 24 h with either 100 microM oleic acid (MUFA) or 100 microM palmitic acid (SFA) and subsequently challenged with GIP, a known stimulator of the L cell. Preexposure to oleic acid but not to palmitic acid significantly increased GIP-induced GLP-1 secretion when compared with controls (55 +/- 12% vs. 34 +/- 9%, P < 0.01). These results demonstrate that the benefit in glycemic tolerance obtained with MUFA diets occurs in association with increased GLP-1 secretion, through a mechanism of enhanced L cell sensitivity. These results suggest that diet therapy with MUFAs may be useful for the treatment of patients with impaired glucose tolerance and/or type 2 diabetes through increased GLP-1 secretion.
富含单不饱和脂肪酸（MUFA）的饮食已被证明有助于血糖控制。此外，MUFA在体外能特异性刺激抗糖尿病激素胰高血糖素样肽-1（GLP-1）的分泌。为了确定MUFA在体内对糖耐量的有益作用是否归因于GLP-1释放增加，将瘦型 Zucker 大鼠成对饲养，给予含5%脂肪的合成饮食，脂肪来源分别为橄榄油（OO；74% MUFA）或椰子油（CO；87%饱和脂肪酸；SFA），持续2周。在喂养期间，两组的食物摄入量和体重增加相似。在口服和十二指肠葡萄糖耐量试验中，OO组的糖耐量均优于CO组[曲线下面积（AUC）分别为121±61 vs. 290±24 mM·120 min，P<0.05；以及112±28 vs. 266±65 mM·120 min，P<0.05]。与CO大鼠相比，OO大鼠肠道胰高血糖素样免疫反应性（gGLI；GLP-1水平的指标）分泌增加（t = 10 min时为402±96 vs. 229±33 pg/ml，P<0.05）。两组之间GLP-1的组织水平、血浆胰岛素和胰高血糖素水平无差异。为了确定GLP-1对OO大鼠糖耐量增强的总贡献，在十二指肠葡萄糖耐量试验前3分钟注入GLP-1受体拮抗剂艾塞那肽（9-39）（Ex(9-39)）。Ex(9-39)消除了OO喂养所带来的糖耐量益处（OO+Ex(9-39) vs. CO+Ex(9-39)，P = 无显著差异），并且与OO对照组相比，OO+Ex(9-39)组的糖耐量恶化（AUC为331±21 vs. 112±28 mM·120 min，P<0.05）。为了探究OO饮食增强GLP-1分泌的机制，将分泌GLP-1的L细胞系分别与100 μM油酸（MUFA）或100 μM棕榈酸（SFA）孵育24小时，随后用已知的L细胞刺激剂葡萄糖依赖性促胰岛素多肽（GIP）进行刺激。与对照组相比，预先暴露于油酸而非棕榈酸显著增加了GIP诱导的GLP-1分泌（55±12% vs. 34±9%，P<0.01）。这些结果表明，MUFA饮食所带来的糖耐量益处与GLP-1分泌增加相关，其机制是L细胞敏感性增强。这些结果提示，通过增加GLP-1分泌，MUFA饮食疗法可能对糖耐量受损和/或2型糖尿病患者的治疗有用。
