游离脂肪酸对基础状态β细胞胰岛素分泌和前胰岛素原mRNA表达的影响

EFFECTS OF FREE FATTY ACIDS ON INSULIN RELEASE AND PREPROINSULINmRNA EXPRESSION IN RAT PANCREATIC β CELLS IN BASAL CONDITION

目的：研究游离脂肪酸（油酸和软脂酸）对基础状态大鼠β细胞胰岛素分泌和前胰岛素原ｍＲＮＡ表达的影响。方法：体外分离培养Ｗｉｓｔａｒ乳鼠β细胞，与软脂酸或油酸共同孵育２４ｈ后，测定胰岛素浓度和３ＨＴｄＲ掺入量，Ｎｏｒｔｈｅｒｎ杂交检测前胰岛素原ｍＲＮＡ表达。结果：（１）软脂酸（０．２５ｍｍｏｌ／Ｌ）或油酸（０．１２５ｍｍｏｌ／Ｌ）组β细胞胰岛素分泌量明显高于对照组。（２）经软脂酸和油酸共同培养２４ｈ后，β细胞３ＨＴｄＲ掺入量增高。（３）软脂酸和油酸试验组β细胞前胰岛素原ｍＲＮＡ表达均高于未经游离脂肪酸培养的对照组。结论：游离脂肪酸可能通过促进基础状态β细胞前胰岛素原ｍＲＮＡ表达和细胞增生，造成基础状态β细胞分泌胰岛素过多，从而参与了高胰岛素血症的发生。

Objective: To investigate the effects of free fatty acids ( palmitate and oleate ) on insulin release and expression of preproinsulin mRNA in rat pancreatic β cells in basal condition. Methods: Pancreatic βcells from newborn Wistar rats were isolated and incubated with free fatty acids. After 24 h exposure to free fatty acids, the insulin release and3HTdR incorporation were assayed. The expression of preproinsulin mRNA was detected by Northern blot hybridization. Results: (1)The insulin secretions of palmitate (0.25 mmol/L) and oleate (0.125 mmol/L) treated βcells were increased. (2) The3HTdR incorporation in βcells cultured with fatty acids was significantly higher than that of βcells cultured without fatty acids. (3) Palmitate and oleate promoted preproinsulin mRNA expression in basal condition. Conclusion: Our data suggest that hyperinsulinemia in obesity is probably induced by high plasma free fatty acids. Free fatty acids increased basal hypersecretion of insulin partly due to βcell hyperplasia and high preproinsulin mRNA expression.