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在未孕和怀孕的斯普拉格-道利大鼠中,使用S-腺苷甲硫氨酸、维生素E和维生素C的协同组合(SAMEC)预防高糖饮食诱导的肝胰岛素抵抗

Prevention of Hepatalin-Dependent Insulin Resistance Induced by a High Sucrose Diet Using a Synergistic Combination of S-Adenosyl Methionine, Vitamin E and Vitamin C (SAMEC) in Virgin and Pregnant Sprague Dawley Rats.

作者信息

Lovat Nicole E J, Chowdhury Kawshik, Legare Dallas J, Lautt W Wayne

机构信息

Firefly Medical Group PLLC, Grand Forks, ND, USA.

SciMar Ltd., Dauphin, Manitoba, R7N 1K4, Canada.

出版信息

J Exp Pharmacol. 2025 May 15;17:193-205. doi: 10.2147/JEP.S508879. eCollection 2025.

Abstract

INTRODUCTION

Storage of nutrient energy from a meal is partitioned in the body approximately equally by insulin (with its known actions on the liver and adipose tissue) and hepatalin (released from the liver with its glycogenic action selectively in skeletal muscle, heart, and kidneys). During healthy pregnancy, there is a late stage mixed insulin resistance involving both insulin and hepatalin. In pregnant rats on a high sucrose diet, hepatalin-dependent insulin resistance (HDIR) develops with unaffected direct insulin action. Compensatory hyperinsulinemia maintains blood glucose level with resultant hypertriglyceridemia and adiposity. Previously, in male Sprague Dawley sucrose-supplemented rats, aged for one year, HDIR and the associated cardiometabolic consequences were prevented by using a targeted synergistic antioxidant cocktail composed of S-Adenosyl-Methionine, vitamin E and vitamin C (SAMEC). The current study tested the hypothesis that SAMEC would confer protection against sucrose-induced HDIR in virgin and pregnant rats.

METHODS

Post-prandial insulin sensitivity was quantified using the rapid insulin sensitivity test (RIST). Sucrose supplementation (35% sucrose in water) was used to induce HDIR in female rats. Eight weeks of normal or SAMEC diet with or without sucrose supplementation was used as an intervention to determine the extent of protection against HDIR by SAMEC in virgin and pregnant rats.

RESULTS AND DISCUSSION

SAMEC administered with the sucrose diet prevented the development of HDIR resulting in normal plasma glucose, insulin, and triglyceride concentrations in both virgin and pregnant groups, and attenuated sucrose-induced fat mass gain in virgin rats. The direct insulin action was unimpaired.

CONCLUSION

SAMEC preserves hepatalin-dependent glucose uptake in virgin and pregnant rats on sucrose supplementation, thus can be used as a preventative in obesity and gestational diabetes.

摘要

引言

餐食中营养能量的储存,在体内大约由胰岛素(其对肝脏和脂肪组织有已知作用)和肝抑素(从肝脏释放,对骨骼肌、心脏和肾脏有选择性糖原生成作用)平均分配。在健康孕期,存在涉及胰岛素和肝抑素的晚期混合性胰岛素抵抗。在高蔗糖饮食的妊娠大鼠中,会出现肝抑素依赖性胰岛素抵抗(HDIR),而直接胰岛素作用未受影响。代偿性高胰岛素血症维持血糖水平,导致高甘油三酯血症和肥胖。此前,在补充蔗糖的一岁雄性斯普拉格 - 道利大鼠中,使用由S - 腺苷甲硫氨酸、维生素E和维生素C组成的靶向协同抗氧化剂鸡尾酒(SAMEC)可预防HDIR及相关的心脏代谢后果。本研究检验了SAMEC能保护未孕和妊娠大鼠免受蔗糖诱导的HDIR影响这一假设。

方法

使用快速胰岛素敏感性试验(RIST)量化餐后胰岛素敏感性。通过补充蔗糖(水中35%蔗糖)诱导雌性大鼠出现HDIR。采用八周正常或SAMEC饮食,有无蔗糖补充作为干预措施,以确定SAMEC对未孕和妊娠大鼠HDIR的保护程度。

结果与讨论

与蔗糖饮食一起给予SAMEC可预防HDIR的发生,使未孕和妊娠组的血浆葡萄糖、胰岛素和甘油三酯浓度正常,并减轻未孕大鼠中蔗糖诱导的脂肪量增加。直接胰岛素作用未受损。

结论

SAMEC可维持补充蔗糖的未孕和妊娠大鼠中肝抑素依赖性葡萄糖摄取,因此可用于预防肥胖和妊娠期糖尿病。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c502/12087585/8e538633242e/JEP-17-193-g0001.jpg

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