Some Musings About Differential Energy Metabolism With Ketogenic Diets

Ketogenic states are of 3 major types: total starvation and those resulting from the consumption of semistarvation, ketogenic diets, and eucaloric ketogenic diets. All are characterized by little or no dietary carbohydrate, resulting in a fat‐based metabolism with sustained ketonemia of varying degrees in each state. The latter 2 diets are clinically useful with important impacts on both aspects of the energy balance equation with increased satiety and less hunger on the intake side and probably increased energy expenditure on the output side; both may have important implications for the successful long‐term management of obesity. Consideration of older research regarding the hormonal response to carbohydrate‐free dieting and recent findings on hepatic glycogen status that occurs with sustained ketonemia support the likelihood that there are profound differences in 24‐hour gluconeogenesis rates between ketogenic diets and balanced diets containing substantial carbohydrate. This metabolic distinction could have a meaningful impact to increase the thermic effect of feeding and daily energy expenditure amounting to 100 kcal/d or more with each of the ketogenic diets.     

苦瓜提取物调节ZDF糖尿病大鼠糖异生的作用机制

目的 观察苦瓜提取物对糖尿病大鼠糖异生信号通路的影响。方法 5~6周龄雄性Zucker Diabetic Fatty（ZDF）大鼠随机分为模型组、苦瓜组（苦瓜提取物0.40 g·kg^-1灌胃）,另7只健康雄性ZDF（fa/+）大鼠为正常组,每日1次灌胃,连续6周。实验过程中,观察大鼠一般情况,记录体质量,第1、3、5周检测空腹血糖、随机血糖;第6周行口服葡萄糖耐量实验（OGTT）、检测大鼠血清甘油三酯（TG）、游离脂肪酸（FFA）、总胆固醇（TC）、天门冬氨酸氨基转移酶（AST）、丙氨酸氨基转移酶（ALT）;肝苏木素-伊红（HE）染色检测肝形态结构;肝糖原染色（PAS）检测肝糖原存储;采用实时荧光定量聚合酶链式反应（Real-time PCR）检测肝脏磷酸稀醇式丙酮酸羧激酶（PEPCK）、葡萄糖-6-磷酸酶（G6Pase）mRNA表达;蛋白免疫印迹法（Western blot）检测肝脏叉头转录因子1（FoxO1）磷酸化水平及磷酸稀醇式丙酮酸羧激酶（PEPCK）、G6Pase蛋白表达。结果 与模型组比较,苦瓜组大鼠体质量、空腹血糖、随机血糖、糖耐量明显改善（P<0.05,P<0.01）;血清FFA、TC、TG明显降低（P<0.05,P<0.01）;ALT、AST各组间差异无统计学意义;HE显示肝细胞排列较整齐,脂肪样变性减轻;PAS显示肝糖原储存增加;肝p-FoxO1蛋白表达显著升高（P<0.01）,FoxO1蛋白表达无显著差异,PEPCK、G6Pase mRNA及蛋白表达明显降低（P<0.05）。结论 苦瓜提取物具有降糖、降脂、改善糖耐量及肝糖原储备作用,与其通过上调FoxO1磷酸化来抑制PEPCK、G6Pase表达,调控糖异生相关。     

Estimating gluconeogenesis by NMR isotopomer distribution analysis of [13C]bicarbonate and [1-13C]lactate

The gluconeogenic contribution to glucose production in livers isolated from rats fasted for 24 h was determined by 13C-NMR isotopomer distribution analysis of secreted glucose enriched from 99% [13C]bicarbonate (n = 4) and 99% [1-13C]lactate (n = 4). Experiments with 3% 2H2O were also performed, allowing the gluconeogenic contribution to be measured by the relative 2H enrichments at positions 5 and 2 of glucose. From 13C-NMR analyses, the contribution of gluconeogenesis to glucose output was estimated to be 93 +/- 3% for [13C]bicarbonate perfusion and 91 +/- 3% for [1-13C]lactate perfusion, in good agreement with the 2H-NMR analysis of the gluconeogenic contribution to glucose production (100 +/- 1% and 99 +/- 1%, respectively) and consistent with the expected negligible contribution from glycogenolysis. These results indicate that 13C-NMR analysis of glucose 13C-isotopomer distribution from either [13C]bicarbonate or [1-13C]lactate precursor provides realistic estimates of the gluconeogenic contribution to hepatic glucose output.     

Changes in plasma glucose and lactate evoked by α and β2-adrenoceptor stimulation in conscious fasted rabbits

In conscious fasted rabbits, the iv infusion of salbutamol (3 micrograms/kg per min) and clonidine (2 micrograms/kg per min) induced a blood glucose increase amenable to blockade, respectively by ICI 118551 (1 micrograms/kg per min) and idazoxan (20 micrograms/kg per min). Amidephrine (10 micrograms/kg per min) and salbutamol mediated an increase in plasma lactate which was attenuated by prazosin (50 micrograms/kg, sc) and ICI 118551 respectively. Clonidine did not alter basal plasma lactate. The iv infusion of adrenaline (0.3 micrograms/kg per min) evoked an increase in plasma lactate more sensitive to blockade by ICI 118551 than by prazosin. ICI 118551 also shortened the hyperglycaemic response to adrenaline, 3-Mercaptopicolinic acid (25 mg/kg) reduced salbutamol- and adrenaline-mediated hyperglycaemia and increased at the same time the lactate/glucose ratio. Our data show that plasma lactate levels may be regulated by alpha 1- and beta 2-excitatory adrenoceptor stimulation. However, only the increase in blood lactate derived from beta 2-adrenergic stimulation seems to contribute to the overall catecholamine-mediated hyperglycaemia.     

NEONATAL HYPOGLYCEMIA AND THE DEVELOPMENT OF GLUCONEOGENETIC ENZYMES

Gluconeogenesis plays an important role in the maintenance of glucose homeostasis in immediate neonatal period. Of the gluconeogenetic enzymes, phosphoenolpyruvate carboxykinase appears only after birth in various species including the human. The development of this enzyme may be crucial for avoiding neonatal hypoglycemia.     

Enzymatic and Metabolic Studies on Carbohydrate and Amino Acid Metabolism in Rat Liver during Acute Uraemia

Abstract. Enzyme activities of the glycolytic, gluconeogenic, and hexose monophosphate pathways were measured in the liver of starved rats 12 and 48 hours after bilateral nephrectomy. Control experiments (sham operated rats) revealed that alterations of enzyme activities were not due to uraemia but to starvation. Alanine-aminotransferase and aspartate- aminotransferase activities, however, were significantly elevated in rat liver 48 hours after nephrectomy when compared with sham operated controls. Concentrations of some of the gluconeogenic intermediates (3-phosphoglyceric acid, pyruvate, phosphoenolpyruvate and glucose-6-phosphate) were significantly higher in the liver of uraemic animals. Amino acid analysis showed an increase in only L-alanine concentration. It is suggested that the elevated content of pyruvate in the liver during acute uraemia is due to an inhibition of pyruvate degradation. Together with the elevated pyruvate concentration the increase in L-alanine could be explained as a consequence of the equilibrium of the alanine-aminotransferase reaction; K_app. of the reaction is not changed by uraemia. Increased activities of the transaminases and the elevated concentrations of the other metabolites measured might indicate that in the liver of nephrectomized rats there is enhanced gluconeogenesis from substrates other than pyruvate.