Alterations in postprandial hepatic glycogen metabolism in type 2 diabetes
Alterations in postprandial hepatic glycogen metabolism in type 2 diabetes
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DOI：
10.2337/diabetes.53.12.3048
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发表时间：
2004-12-01
期刊：
影响因子：
7.7
通讯作者：
Roden, M
中科院分区：
文献类型：
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作者：
Krssak, M;Brehm, A;Roden, M
骨骼肌葡萄糖处置减少和内源性葡萄糖产生（EGP）增加导致2型糖尿病患者餐后高血糖，但肝糖原代谢的作用仍不确定。应用C-13核磁共振波谱（NMRS）和可变输注双示踪技术监测2型糖尿病患者和非糖尿病志愿者对照组（CON）在混合餐摄入后和高血糖-高胰岛素-生长抑素钳夹期间的肝糖原代谢和EGP。通过H-1 NMRS定量肝细胞脂质（HCL）含量。晚餐前，2型糖尿病患者的肝糖原较低（227 +/- 6 vs. CON：275 +/- 10 mmol/l肝脏，P < 0.001）。进食后，净合成率分别为0.76 +/- 0.16（2型糖尿病患者）和1.36 +/- 0.15 mg（.）kg（-1）（.）min（-1）（CON，P < 0.02），导致峰值浓度为283 +/- 15和360 +/- 11 mmol/l肝脏。EGP的餐后率与0.3mg（.）kg（-1）（.）min（-1）（30-170 min; P < 0.05 vs. CON）在2型糖尿病患者中更高。钳夹条件下，2型糖尿病患者肝糖原净合成减少54%（P < 0.03），0.5mg（.）kg（-1）（.）min（-1）时EGP升高（P < 0.02）。肝葡萄糖储备与HCL含量呈负相关（R =-0602，P < 0.05）。类型. 2例糖尿病患者表现出1）餐后肝糖原合成减少，2）EGP抑制暂时受损，3）这些缺陷未通过控制高血糖高胰岛素血症正常化。因此，除了胰岛素-胰高血糖素比率改变或游离脂肪酸增加的影响外，胰岛素敏感性受损和/或慢性胰高血糖素毒性也是2型糖尿病患者肝糖原代谢缺陷的原因。
Decreased skeletal muscle glucose disposal and increased endogenous glucose production (EGP) contribute to postprandial hyperglycemia in type 2 diabetes, but the contribution of hepatic glycogen metabolism remains uncertain. Hepatic glycogen metabolism and EGP were monitored in type 2 diabetic patients and nondiabetic volunteer control subjects (CON) after mixed meal ingestion and during hyperglycemic-hyperinsulinemic-somatostatin clamps applying C-13 nuclear magnetic resonance spectroscopy (NMRS) and variable infusion dual-tracer technique. Hepatocellular lipid (HCL) content, was quantified by H-1 NMRS. Before dinner, hepatic glycogen was lower in type 2 diabetic patients (227 +/- 6 Vs. CON: 275 +/- 10 mmol/l liver, P < 0.001). After meal ingestion, net synthetic rates were 0.76 +/- 0.16 (type 2 diabetic patients) and 1.36 +/- 0.15 mg (.) kg(-1) (.) min(-1) (CON, P < 0.02), resulting in peak concentrations of 283 +/- 15 and 360 +/- 11 mmol/l liver. Postprandial rates of EGP were similar to0.3 mg (.) kg(-1) (.) min(-1) (30-170 min; P < 0.05 vs. CON) higher in type 2 diabetic patients. Under clamp conditions, type 2 diabetic patients featured similar to54% lower (P < 0.03) net hepatic glycogen synthesis and similar to0.5 mg (.) kg(-1) (.) min(-1) higher (P < 0.02) EGP. Hepatic glucose storage negatively correlated with HCL content (R = -0 602, P < 0.05). Type. 2 diabetic patients exhibit 1) reduction of postprandial hepatic glycogen synthesis, 2) temporarily impaired suppression of EGP, and 3) no normalization of these defects by controlled hyperglycemic hyperinsulinemia. Thus, impaired insulin sensitivity and/or chronic glucolipiotoxicity in addition to the effects of an altered insulin-to-glucagon ratio or increased free fatty acids accounts for defective hepatic glycogen metabolism in type 2 diabetic patients.