精氨酸代谢在 A-β+酮症倾向糖尿病的成年人中发生改变。
Arginine Metabolism Is Altered in Adults with A-β + Ketosis-Prone Diabetes.
机构信息
Diabetes Research Center, Division of Diabetes, Endocrinology and Metabolism.
USDA-ARS Children's Nutrition Research Center, Department of Pediatrics; and Alkek Center for Metagenomics and Microbiome Research, Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX.
出版信息
J Nutr. 2018 Feb 1;148(2):185-193. doi: 10.1093/jn/nxx032.
BACKGROUND
A-β + ketosis-prone diabetes (KPD) is a subset of type 2 diabetes in which patients have severe but reversible β cell dysfunction of unknown etiology. Plasma metabolomic analysis indicates that abnormal arginine metabolism may be involved.
OBJECTIVE
The objective of this study was to determine the relation between gut microbiome and arginine metabolism and the relation between arginine availability and β cell function in KPD patients compared with control participants.
METHODS
Kinetics of arginine and related metabolites were measured with stable isotope tracers, and insulin secretory responses to arginine and glucose were determined under euglycemic and hyperglycemic conditions in 6 KPD patients and 6 age-, gender-, and body mass index-matched control participants. Glucose potentiation of arginine-induced insulin secretion was performed in a different set of 6 KPD and 3 control participants.
RESULTS
Arginine availability was higher in KPD patients during euglycemia [53.5 ± 4.3 (mean ± SEM) compared with 40.3 ± 2.4 μmol · kg lean body mass (LBM)-1 · h-1, P = 0.03] but declined more in response to hyperglycemia (Δ 10.15 ± 2.6 compared with Δ 3.20 ± 1.3 μmol · kg LBM-1 · h-1, P = 0.041). During hyperglycemia, ornithine flux was not different between groups but after an arginine bolus, plasma ornithine AUC trended higher in KPD patients (3360 ± 294 compared with 2584 ± 259 min · μmol · L-1, P = 0.08). In both euglycemia and hyperglycemia, the first-phase insulin responses to glucose stimulation were lower in KPD patients (euglycemic insulin AUC 282 ± 108 compared with 926 ± 257 min · μU · mL-1, P = 0.02; hyperglycemic insulin AUC 358 ± 79 compared with 866 ± 292 min · μU · mL-1, P = 0.05), but exogenous arginine restored first-phase insulin secretion in KPD patients to the level of control participants.
CONCLUSION
Compared with control participants, KPD patients have increased arginine availability in the euglycemic state, indicating a higher requirement. This is compromised during hyperglycemia, with an inadequate supply of arginine to sustain metabolic functions such as insulin secretion. Exogenous arginine administration restores a normal insulin secretory response.
背景
A-β+酮症倾向糖尿病（KPD）是 2 型糖尿病的一个亚型，其患者β细胞功能严重但可逆转，病因不明。血浆代谢组学分析表明，异常的精氨酸代谢可能与之相关。
目的
本研究旨在确定 KPD 患者与对照组相比，肠道微生物组与精氨酸代谢之间的关系，以及精氨酸可用性与β细胞功能之间的关系。
方法
采用稳定同位素示踪技术测量精氨酸及相关代谢物的动力学，在 6 例 KPD 患者和 6 例年龄、性别和体重指数匹配的对照组参与者中，分别在正常血糖和高血糖条件下测定精氨酸和葡萄糖诱导的胰岛素分泌反应。在另一组 6 例 KPD 患者和 3 例对照组参与者中进行葡萄糖增强的精氨酸诱导胰岛素分泌作用。
结果
KPD 患者在正常血糖时精氨酸的可用性较高[53.5±4.3（均数±标准差）与 40.3±2.4 μmol·kg 去脂体重（LBM）-1·h-1，P=0.03]，但对高血糖的反应下降较多（Δ10.15±2.6 与 Δ3.20±1.3 μmol·kg LBM-1·h-1，P=0.041）。高血糖时，两组间鸟氨酸通量无差异，但在精氨酸冲击后，KPD 患者的血浆鸟氨酸 AUC 趋势较高（3360±294 与 2584±259 min·μmol·L-1，P=0.08）。在正常血糖和高血糖时，KPD 患者葡萄糖刺激的第一时相胰岛素反应较低（正常血糖时胰岛素 AUC 为 282±108 与 926±257 min·μU·mL-1，P=0.02；高血糖时胰岛素 AUC 为 358±79 与 866±292 min·μU·mL-1，P=0.05），但外源性精氨酸可使 KPD 患者的第一时相胰岛素分泌恢复至对照组水平。
结论
与对照组相比，KPD 患者在正常血糖状态下精氨酸的可用性增加，表明其需求增加。在高血糖时，这种供应不足会影响胰岛素分泌等代谢功能。外源性精氨酸给药可恢复正常的胰岛素分泌反应。
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