Belfiore F, Iannello S, Rabuazzo A M, Campione R
Chair of Pathophysiology of Metabolism, University of Catania Medical School, Ospedale Garibaldi, Italy.
Int J Obes. 1987;11(6):631-40.
The aim of this study was to investigate the metabolic effects of short-term fasting in obese diabetic patients and to correlate the observed changes with the activity of hepatic key enzymes in an animal model of obesity-associated diabetes (ob/ob mice, C57BL/6J strain). In obese diabetic patients (ODP), a 72-h fast (causing slight change in body weight) decreased fasting glycemia by 3.82 +/- 0.79 mmoles/l and significantly improved glucose tolerance (OGTT) while reducing basal and stimulated insulinemia, whereas in obese non-diabetic patients (ONDP) only a small decrease in fasting glycemia (1.24 +/- 0.51 mmoles/l) occurred. This suggests that in ODP hyperphagia is a factor contributing to maintain hyperglycaemia and glucose intolerance (in the face of hyperinsulinaemia, indicating insulin resistance). In fed obese hyperglycaemic mice (OHM), which are a good model of the human obesity-associated diabetes, hepatic fructose-1,6-diphosphatase (F16Pase) and glucose-6-phosphatase (G6Pase), involved in glucose production, showed increased activity (+52 and +200 per cent, respectively) compared to control mice (CM), and the ratios of F16Pase and G6Pase to the opposing enzymes phosphofructokinase (PFK1) and glucokinase (GK), i.e. the F16Pase/PFK1 and G6Pase/GK ratios, were increased by 38 and 101 per cent, respectively, suggesting increase in gluconeogenesis and perhaps in glycogenolysis. In the 48-h fasted OHM, F16Pase activity was decreased (-30 per cent) compared to the fed animals, while the activity of G6Pase showed a smaller and statistically not significant change (-22 per cent). In contrast, in the CM a 48-h fasting was associated with a trend toward increased F16Pase (+22 per cent) and G6Pase (+173 per cent). However, since PFK1 and GK decreased to a similar extent in OHM and CM, the F16Pase/PFK1 and G6Pase/GK ratios, basally elevated in the OHM, did not change with fasting, whereas in the CM they showed a striking elevation (+71 and +274 per cent, respectively). The basally elevated F16Pase/PFK1 and G6Pase/GK ratios (functionally linked to glucose production) in the OHM may contribute to maintain hyperglycaemia; in these mice, the lack of further increase in the glucose production-related F16Pase/PFK1 and G6Pase/GK ratios (which occurs in CM) with fasting might allow that the interruption of the afflux of dietary carbohydrates ameliorates the glycaemic level. Similar mechanisms might occur also in the ODP.
本研究的目的是调查短期禁食对肥胖糖尿病患者的代谢影响，并将观察到的变化与肥胖相关糖尿病动物模型（ob/ob小鼠，C57BL/6J品系）中肝脏关键酶的活性相关联。在肥胖糖尿病患者（ODP）中，72小时禁食（导致体重略有变化）使空腹血糖降低了3.82±0.79毫摩尔/升，并显著改善了葡萄糖耐量（口服葡萄糖耐量试验），同时降低了基础和刺激状态下的胰岛素血症，而在肥胖非糖尿病患者（ONDP）中，仅空腹血糖有小幅下降（1.24±0.51毫摩尔/升）。这表明在ODP中，食欲亢进是导致高血糖和葡萄糖不耐受（尽管存在高胰岛素血症，表明存在胰岛素抵抗）持续存在的一个因素。在喂食的肥胖高血糖小鼠（OHM）中，它们是人类肥胖相关糖尿病的良好模型，参与葡萄糖生成的肝脏果糖-1,6-二磷酸酶（F16Pase）和葡萄糖-6-磷酸酶（G6Pase）与对照小鼠（CM）相比，活性增加（分别增加了+52%和+200%），并且F16Pase和G6Pase与相反的酶磷酸果糖激酶（PFK1）和葡萄糖激酶（GK）的比率，即F16Pase/PFK1和G6Pase/GK比率，分别增加了38%和101%，表明糖异生增加，可能糖原分解也增加。在禁食48小时的OHM中，与喂食的动物相比，F16Pase活性降低（-30%），而G6Pase活性变化较小且无统计学意义（-22%）。相反，在CM中，48小时禁食与F16Pase（+22%）和G6Pase（+173%）活性增加的趋势相关。然而，由于PFK1和GK在OHM和CM中下降程度相似，OHM中基础升高的F16Pase/PFK1和G6Pase/GK比率在禁食时没有变化，而在CM中它们显著升高（分别增加了+71%和+274%）。OHM中基础升高的F16Pase/PFK1和G6Pase/GK比率（在功能上与葡萄糖生成相关）可能有助于维持高血糖；在这些小鼠中，与禁食相关的葡萄糖生成相关的F16Pase/PFK1和G6Pase/GK比率（在CM中出现）没有进一步增加，这可能使得膳食碳水化合物流入的中断改善了血糖水平。类似的机制也可能发生在ODP中。
