Sources of plasma glucose by automated Bayesian analysis of 2H NMR spectra.

Sources of blood glucose can be determined after oral ingestion of (2)H(2)O followed by isolation of plasma glucose and measurement of the relative (2)H enrichments in select positions within the glucose molecule. Typically, (2)H enrichments are obtained by mass spectrometry but (2)H NMR offers an alternative. Here it is demonstrated that the entire analysis may be automated by Bayesian analysis of a (2)H free induction decay signal of monoacetone glucose to obtain a direct readout of the relative contributions of glycogenolysis, glycerol, and phosphoenol pyruvate to plasma glucose production. Furthermore, Markov Chain Monte Carlo (MCMC) simulations of the posterior probability density provide uncertainties in all metabolic parameters from a single patient, thereby allowing comparisons in glucose metabolism from one individual to another. The combined MCMC Bayesian methodology is operationally simple and requires little intervention from the operator.     

Sources of hepatic glycogen synthesis during an oral glucose tolerance test: Effect of transaldolase exchange on flux estimates

Sources of hepatic glycogen synthesis during an oral glucose tolerance test were evaluated in six healthy subjects by enrichment of a 75‐g glucose load with 6.67% [U‐¹³C]glucose and 3.33% [U‐²H₇]glucose and analysis of plasma glucose and hepatic uridine diphosphate–glucose enrichments (sampled as urinary menthol glucuronide) by ²H and ¹³C nuclear magnetic resonance. The direct pathway contribution, as estimated from the dilution of [U‐¹³C]glucose between plasma glucose and glucuronide, was unexpectedly low (36 ± 5%). With [U‐²H₇]glucose, direct pathway estimates based on the dilution of position 3 ²H‐enrichment between plasma glucose and glucuronide were significantly higher (51 ± 6%, P = 0.05). These differences reflect the exchange of the carbon 4, 5, and 6 moiety of fructose‐6‐phosphate and glyceraldehyde‐3‐phosphate catalyzed by transaldolase. As further evidence of this exchange, ²H‐enrichments in glucuronide positions 4 and 5 were inferior to those of position 3. From the difference in glucuronide positions 5 and 3 enrichments, the fraction of direct pathway carbons that experienced transaldolase exchange was estimated at 21 ± 4%. In conclusion, the direct pathway contributes only half of hepatic glycogen synthesis during an oral glucose tolerance test. Glucose tracers labeled in positions 4, 5, or 6 will give significant underestimates of direct pathway activity because of transaldolase exchange. Magn Reson Med, 2009. © 2009 Wiley‐Liss, Inc.     

Quantifying hepatic glycogen synthesis by direct and indirect pathways in rats under normal ad libitum feeding conditions

Hepatic glycogen synthesis from intact hexose (direct pathway) relative to that from gluconeogenic precursors (indirect pathway) was quantified in ad libitum‐fed rats. Following ²H₂O administration and overnight feeding, the livers were removed and glycogen ²H‐enrichment was measured by ²H NMR. Six controls and six rats rendered hyperglycemic by streptozotocin (STZ; fasting blood glucose = 385 ± 31 mg/dl) were studied. The indirect pathway contribution, estimated as glycogen hydrogen 5 relative to hydrogen 2 enrichment, was 54% ± 4% for control rats—similar to values from healthy, meal‐fed humans. In STZ‐treated rats, the indirect pathway contribution was significantly higher (68% ± 4%, P < 0.05 vs. controls), similar to that of Type 1 diabetic (T1D) patients. In conclusion, sources of hepatic glycogen synthesis in rats during ad libitum nocturnal feeding were quantified by analysis of glycogen enrichment from ²H₂O. STZ caused alterations resembling the pathophysiology of hepatic glycogen synthesis in T1D patients. Magn Reson Med 61:1–5, 2009. © 2008 Wiley‐Liss, Inc.     

大麻二酚缓解高脂饮食老龄小鼠肝脏脂肪变性的实验研究

目的 探究大麻二酚(cannabidiol, CBD)对高脂饮食老龄小鼠肝脏脂肪变性的保护作用及其信号机制。方法 30只老龄雄性C57BL/6J小鼠随机分为三组：正常饮食组(NC组;基础饲料)、高脂饮食组(HFD组;高脂饲料)和CBD治疗组(CBD组;高脂饲料加大麻二酚治疗)。12周后,测定各组小鼠血清葡萄糖、三酰甘油(TG)、总胆固醇(TC)、丙氨酸转氨酶(ALT)和天冬氨酸转氨酶(AST)、胰岛素、游离脂肪酸(FFA)。葡萄糖耐量实验(IPGTT)和胰岛素耐量实验(ITT)检测小鼠糖处理能力。油红O染色检测小鼠肝脏的脂质沉积情况。qRT-PCR检测脂代谢相关基因的mRNA表达,Western blot检测腺苷酸激活蛋白激酶(AMPK)及乙酰辅酶A羧化酶(ACC)蛋白水平。结果 与NC组比较,HFD组小鼠的血糖、TG、TC、FFA、ALT及AST均显著升高,肝脏脂质沉积增加(P<0.05)。CBD组的上述糖脂代谢相关指标明显降低(P<0.05),小鼠对葡萄糖的处理能力提高,肝脏脂质沉积减轻,脂代谢相关基因的mRNA表达水平降低(P<0.05)。CBD显著增加磷酸化A...     

博苏对高血压合并2型糖尿病患者糖、脂代谢影响的临床观察

目的观察博苏对高血压合并2型糖尿病患者糖、脂代谢的影响及降压效果.方法将经1周的洗脱期后入选的30例患者随机分为两组,一组服用博苏,另一组服用依那普利,2周调整1次剂量,若剂量加倍后仍SBP＞130mmHg和（或）DBP＞85mmHg,两组均加用尼群地平调整剂量至BP≤130/85mmHg.观察治疗前和治疗12周后空腹和餐后2h血糖、HbA1c、TC、TG、HDL和血压的变化.结果博苏组治疗前后空腹和餐后2h血糖、HbA1c、TC、TG、HDL无明显变化（P＞0.05）,两组间亦无显著性差异（P＞0.05）.博苏和依那普利均能显著降压（P＜0.01）.结论博苏在安全降压的同时并不影响糖代谢和脂代谢.