高血压和糖代谢调节异常对动脉硬化的影响

高血压和糖代谢调节异常是动脉硬化的促发因素,动脉硬化为心血管事件致病关键环节,考虑到动脉硬化程度评估在心脑疾病方面的潜在作用,脉搏波速度和踝臂指数作为无创的评估动脉僵硬度和动脉阻塞程度的指标,其作用也正日益引起重视。本文主要讨论高血压和糖代谢异常对动脉硬化的促进作用以及对动脉硬化早期评估的意义。     

Glucoregulation and hormonal changes during prolonged exercise in boys and girls

A group of 17 children, 8.5–11 years old, performed a 60-min cycle exercise at 60% of maximal oxygen uptake (VO_2max) 2 h after a standardized breakfast. They were 10 young boys (pubertal stage =1) and 7 young girls (pubertal stage 2) of similarVO_2max (respective values were 48.5 ml min^–1 kg^–1, SEM 1.8; 42.1 ml min^–1 kg^–1, SEM 2.4). Blood samples of 5 ml were withdrawn by heparinized catheter, the subjects being in a supine position, 30 min before the test, then after 0, 15, 30 and 60 min of exercise and following 30 min recovery. Haematocrit was immediately measured. Thereafter plasma was analysed for glucose, non-esterified fatty acid, glycerol, catecholamine (noradrenaline, adrenaline), insulin and glucagon concentrations. This study showed two main results. First, the onset of exercise induced a significant glucose decrease (of about 11,4%) in all the children. Secondly, both the glycaemic and the hormonal responses were obviously different according to the sex. In boys only, the initial glucose drop was significantly correlated to the pre-exercise insulin values. Whatever the time, the glycaemic levels and the catecholamine responses were lower in girls than in boys, whereas the insulin values remained higher. However, none of these two hormonal parameters seemed to be really responsible for the lower glucose values in girls. On the one hand, the great individual variability of noradrenaline and adrenaline and differences in their relative intensity at the end of the exercise between boys and girls might contribute to the lower catecholamine levels in girls. On the other hand, the lack of a significant relationship in girls between the glucose decrease after exercise and the pre-exercise insulin values might be explained by a relative insulin insensitivity concomitant with the earlier growth spurt in girls, as demonstrated in subjects at rest by other authors. Finally the mechanisms of all these gender differences remain to be clarified and might be accounted for by a different maturation level in boys and girls.     

A role for central postsynapticα2-adrenoceptors in glucoregulation

Central or peripheral administration of theα₂-adrenoceptor agonist clonidine causes marked hyperglycemia in the rat. It is not clear whether this effect is mediated within the brain at either pre- or postsynapticα₂-adrenoceptors or whether it is due to peripheralα₂-agonist actions. We employed computerized mass spectrometry to measure noradrenaline (NA) and its primary neuronal metabolite 3,4-dihydroxyphenylglycol (DHPG) in the medial basal hypothalamus of rats treated acutely with clonidine, theα₂-antagonist yohimbine, the postganglionic noradrenergic blocker guanethidine and the neuroglycopenic agent 2-deoxy-d-glucose (2-DG). That clonidine's hyperglycemic effect was due, in part, to an action at centralα₂-adrenoceptors was indicated by the ability of guanethidine to significantly inhibit the glucose response. Because of clonidine's inhibition of hypothalamic NA release (assessed by the DHPG/NA ratio), presumably by presynaptic agonism, these data indicated that postsynaptic receptor stimulation by clonidine was involved in activating glucose release. Yohimbine markedly increased the hypothalamic DHPG/NA ratio, reflecting presynaptic stimulation of NA release, but at the same time inhibited the hyperglycemic response due to 2-DG administration. This latter effect to block hyperglycemia is consistent with antagonism of postsynapticα₂-adrenoceptors involved in mediating hepatic glucose output. These data indicate a major role for postsynapticα₂-adrenoceptors in glucoregulation.     

Visceral factors in the control of food intake

Some years ago, we reported that the increased blood intake of hypoglycemic rats was inhibited by the intravenous infusion of fructose, a sugar that cannot cross the blood-brain barrier and nourish cerebral chemoreceptors. More recent experiments therefore have focused on visceral factors in the control of food intake. Three observations have been emphasized in this review. First, we found that gastric emptying was increased during insulin-induced hypoglycemia, and that this effect also was eliminated by administration of fructose. Hepatic vagotomy abolished both this effect of fructose on gastric emptying and its effect on food intake. Second, we found that in rats with severe diabetes, the rate of gastric emptying did decrease in proportion to increasing concentration of an administered glucose load, as it does in intact rats, but calories emptied more rapidly than normal regardless of the concentration of the load. Third, we found that rats with varying degrees of streptozotocin-induced damage to the pancreas ate more food than intact rats did after an overnight fast, and that individual intakes were proportional to the induced glucose intolerance. The increased eating took the form of shorter intermeal intervals, as if the initial postfast meal did not remain satiating for a normal amount of time. These and other findings suggest that food intake is controlled in part by satiety signals apparently related to the delivery of utilizable calories plus insulin to the liver. These signals also seem to affect gastric emptying and thereby might influence other satiety signals related to gastric distention.     

Loss of feeding in response to 2-deoxy-D-glucose but not insulin after zona incerta lesions in the rat

Bilateral lesions in the anterior aspects of the zona incerta of male rats reliably reduced the feeding response to systemically administered 2-deoxy-D-glucose. Insulin-induced feeding remained intact. Zona incerta lesions may interrupt central vagal projections important for the feeding response to cellular glucoprivation.     

Glucoregulatory and order effects on verbal episodic memory in healthy adolescents after oral glucose administration

The ingestion of oral glucose has been observed to facilitate memory performance in both elderly individuals and in young adults. However, fewer studies have investigated the effect of glucose on memory in children or adolescents. In the present study, the ingestion of a glucose laden drink was observed to enhance verbal episodic memory performance in healthy adolescents under conditions of divided attention, relative to a placebo drink. Further analyses found that this glucose memory facilitation effect was observed only in adolescents exhibiting better glucoregulatory efficiency. These findings demonstrate that the glucose memory facilitation effect can be generalised to younger individuals. The importance of controlling for treatment order in within-subjects designs investigating the glucose memory enhancement effect is also discussed.     

Long-term effects of insulin in weanling rats with dorsomedial hypothalamic hypophagia: Food intake,efficiency of food utilization,body weight and composition

Twenty-five day-old Sprague-Dawley rats received electrolytic lesions in the dorsomedial hypothalamic nuclei (DMNL rats); sham-operated rats served as controls. Two weeks after the operation the DMNL rats showed reduced (p<0.001) body weight and food intake but normal body composition (Lee Index) and efficiency of food utilization (EFU). During the following 32 days subcutaneous administration twice daily of intermediary-acting insulin in increasing doses (mean daily dose 2.64 IU/kg) caused highly significant increases in food intake in both groups. Injection for the subsequent 14 days of higher doses of insulin (mean daily dose 5.64 IU/kg) caused dramatic increase in both food intake and Lee Index and equalized the rate of weight gain with that of the controls. However, in absolute terms the DMNL rats remained consistently hypophagic and weighed significantly less than the controls. Both DMNL rats and controls showed the same EFU during both periods of insulin administration. On discontinuation of hormone treatment during the subsequent 20 days, food intake and body weight gains returned to pretreatment values and the insulin-induced increased Lee Index returned into the low-normal range. However, EFU was significantly (p<0.05) decreased during this period. At sacrifice, plasma glucose, glycerol, free fatty acids and total protein and carcass lipid and protein were normal in the DMNL rats. Absolute and relative (per 100 g body weight and per metabolic size) weight of epididymal fat pads, pituitaries, adrenals and kidneys were normal in the DMNL rats but testes weight per 100 g body weight was higher (p<0.05) in the DMNL rats. Although DMN lesions may remove some glucose-sensitive elements within the hypothalamus, the animals are still capable of responding to the food intake and weight-promoting properties of insulin, as do intact animals.     

Stimulation of 5-hydroxytryptamine nerve cells in dorsal and median raphe nuclei elevates blood glucose in rats

The role played by dorsal or median raphe nuclei in glucoregulation was investigated by stimulating these nuclei in normal rats and in rats with chemical ablation of the hydroxytryptamine (5-HT) nerve cells in these nuclei. Electrical stimulation of either dorsal or median raphe nuclei increased blood glucose or the in vivo voltammetric signal of hypothalamic 5-OH-indole in normal rats; the increase in blood glucose level or the hypothalamic 5-OH-indole release was proportional to the intensity of stimulation. Microinjection of kainic acid or l-glutamate at the same sites also produced hyperglycemia or stimulated the hypothalamic 5-OH-indole release. This stimulation-induced hyperglycemia was significantly reduced by pretreatment of animals with spinal transection or adrenalectomy. In addition, selective destruction of the hypothalamic 5-HT nerve fibers, produced by administration of 5,7-di-hydroxytryptamine (a 5-HT nerve depletor) into both dorsal and median raphe regions, reduced the magnitude of the hyperglycemic responses to electrical stimulation of either dorsal or median raphe nuclei. The data indicate that stimulation of ascending 5-HT pathways in the rat's brain increases the adrenal-sympathetic efferent activity and leads to hyperglycemia.