IMPAIRED NET HEPATIC GLYCOGEN-SYNTHESIS IN INSULIN-DEPENDENT DIABETIC SUBJECTS DURING MIXED MEAL INGESTION - A C-13 NUCLEAR-MAGNETIC-RESONANCE SPECTROSCOPY STUDY
IMPAIRED NET HEPATIC GLYCOGEN-SYNTHESIS IN INSULIN-DEPENDENT DIABETIC SUBJECTS DURING MIXED MEAL INGESTION - A C-13 NUCLEAR-MAGNETIC-RESONANCE SPECTROSCOPY STUDY
复制标题
DOI：
10.1172/jci117727
复制
发表时间：
1995-02-01
影响因子：
15.9
通讯作者：
SHULMAN, GI
中科院分区：
文献类型：
--
作者：
HWANG, JH;PERSEGHIN, G;SHULMAN, GI
使用 C-13 核磁共振波谱法测量了 6 名胰岛素依赖型糖尿病 (IDDM) 受试者和 9 名体重匹配的对照受试者在一天中摄入三份等热量混合餐的肝糖原浓度。还使用[1-C-13]葡萄糖与对乙酰氨基酚组合来评估肝糖原合成的直接和间接（3个碳单位-->->糖原）途径的相对通量，以无创地对肝UDP-葡萄糖库进行取样。两组的平均空腹肝糖原含量相似。每餐后，两组的肝糖原含量均增加，并在餐后4-5小时达到峰值。晚上 11:00 之前IDDM 受试者仅合成了对照组合成的糖原的 30% [IDDM 受试者，净增量 = 44 +/- 20（平均值 +/- SE）mM；对照受试者，净增量 = 144 +/- 14 mM； P<0.05]。早餐后，IDDM 受试者中通过糖异生途径相对于肝糖原合成直接途径的通量 (59 +/- 4%) 是对照受试者 (35 +/- 4%，P < 0.0003) 的 1.7 倍。总之，在混合膳食条件下，IDDM 控制不佳的受试者在净肝糖原合成和增强的肝糖异生方面存在重大缺陷。前一种异常可能导致对反调节激素的血糖反应受损，而两种异常都可能导致餐后高血糖。
Hepatic glycogen concentration was measured in six subjects with insulin-dependent diabetes mellitus (IDDM) and nine weight-matched control subjects using C-13 nuclear magnetic resonance spectroscopy during a day in which three isocaloric mixed meals were ingested. The relative fluxes of the direct and indirect (3 carbon units --> --> glycogen) pathways of hepatic glycogen synthesis were also assessed using [1-C-13]glucose in combination with acetaminophen to noninvasively sample the hepatic UDP-glucose pool. Mean fasting hepatic glycogen content was similar in the two groups. After each meal, hepatic glycogen content increased, peaking 4-5 h after the meal in both groups. By 11:00 p.m. the IDDM subjects had synthesized only 30% of the glycogen that was synthesized by the control group [IDDM subjects, net increment = 44 +/- 20 (mean +/- SE) mM; control subjects, net increment = 144 +/- 14 mM; P < 0.05]. After breakfast the flux through the gluconeogenic pathway relative to the direct pathway of hepatic glycogen synthesis was 1.7-fold greater in the IDDM subjects (59 +/- 4%) than in the control subjects (35 +/- 4%, P < 0.0003). In conclusion, under mixed meal conditions, subjects with poorly controlled IDDM have a major defect in net hepatic glycogen synthesis and augmented hepatic gluconeogenesis. The former abnormality may result in an impaired glycemic response to counterregulatory hormones, whereas both abnormalities may contribute to postprandial hyperglycemia.