Amiloride-blockable Ca2+-activated Na+-permeant channels in the fetal distal lung epithelium

The Na⁺ transport function of alveolar epithelium represents an important mechanism for clearance of fluid in air space at birth. I observed the activity of two types of amiloride-blockable Na⁺-permeant cation channels in the apical membrane of fetal distal lung epithelium cultured on permeable filters for 2 days after harvesting of the cells from Wistar rats of 20 days' gestation (term = 22 days). One type was a nonselective cation (NSC) channel and had a linear current/voltage (I/V) relationship with a single-channel conductance of 26.9 ± 0.8 pS (n = 5). The other type was highly Na⁺ selective (i.e. Na⁺ channel) and had an inwardly rectifyingI/V relationship with a single-channel conductance of 11.8 ± 0.2 pS (n = 5) around resting membrane potential. The NSC channel was more frequently observed (1.37 ± 0.15 per patch membrane;n = 73) than the Na⁺ channel (0.15 ± 0.40 per patch membrane;n = 73). However, the open probability of the NSC channel was smaller than that of the Na⁺ channel. Both types of the channels were activated by cytosolic Ca²⁺, however the sensitivity to cytosolic Ca²⁺ was much higher in the Na⁺ channel than in the NSC channel. Furthermore, both types of the channels were blocked by amiloride or benzamil. The half-maximal inhibitory concentration (IC₅₀) of amiloride or benzamil of the Na⁺ channel was 1–2 M, while that of NSC channel was less than 1 M. Both channels were activated by insulin.     

胰岛素、可地松和已烯雌酚处理妊娠早期小鼠对其胚胎发育的影响

本文用不同剂量的胰岛素、可地松、已烯雌酚,作用于妊娠开始至80小时的昆明小鼠,然后观察胚胎早期(植入前)和胚胎晚期(妊娠18天)的胚胎数量、发育时期及其与黄体数相比成活率的变化。实验表明,用较大剂量激素处理后,早期胚胎的上述各项指标,均表现出十分明显的抑制效果。当剂量逐渐降低后,仍表现出不同程度的抑制作用,只是逐渐趋于正常。所用各种激素对晚期胚胎的影响,表现在除部分死亡外,存活者的生长和发育一直落后。说明妊娠早期小鼠体内某些激素的水平,不仅直接影响早期,而且也影响晚期胚胎的发育。     

Oxidative stress, ER stress, and the JNK pathway in type 2 diabetes

Pancreatic -cell dysfunction and insulin resistance are observed in type 2 diabetes. Under diabetic conditions, oxidative stress and ER stress are induced in various tissues, leading to activation of the JNK pathway. This JNK activation suppresses insulin biosynthesis and interferes with insulin action. Indeed, suppression of the JNK pathway in diabetic mice improves insulin resistance and ameliorates glucose tolerance. Thus, the JNK pathway plays a central role in pathogenesis of type 2 diabetes and may be a potential target for diabetes therapy.     

Effects of exercise cessation on lipids and lipoproteins in distance runners and power athletes

Summary The purpose of this study was to determine the effects of short-term exercise cessation on lipid and lipoprotein profile and insulin sensitivity in highly trained runners (n=12; mean age 19.9 years) and power athletes (n=12; mean age 24.4 years). Following 14 days of exercise cessation, running time to exhaustion and maximal oxygen uptake decreased by 9.2% and 4.8% (P < 0.05) in the runners, while in the power athletes one repetition maximum squat and bench press did not change (P>0.05). No changes occurred in body composition. Data from a 2-h oral glucose tolerance test revealed an impairment of the glycemic state in all athletes (P<0.05). In contrast, exercise cessation did not significantly (P>0.05) alter plasma levels of cholesterol, triglycerides, and low density (LDL) and high density lipoprotein (HDL). No changes were observed in HDL₂, HDL_2b, and HDL₃ subfractions, LDL diameter, and qualitative LDL pattern (P>0.05). These data thus suggest that despite a decrease in insulin sensitivity, short-term exercise cessation, independent of exercise mode, was insufficient to alter plasma lipid and lipoprotein profiles in well-trained athletes.     

胰岛素对白细胞介素1产生及作用的影响

本文研究胰岛素对白细胞介素1(IL—1)的产生及其作用的影响.实验证实:腴岛素能促进LPS刺激的巨噬细胞IL—1的产生,并可增强胸腺细胞对Con A的反应.但用尼龙毛处理胸腺细胞除去粘附细胞后,胸腺细胞在无外源性IL—1存在时,对Con A的反应很弱.胰岛素不能增强经尼龙毛处理后的胸腺细胞对Con A的反应.加入外源性IL—1后,胰岛素可显著增强胸腺细胞对IL—1的应答,促进细胞增殖.这些结果表明。胰岛素是通过促进IL—1的产生及增强其作用来调节激活T细胞的.     

Meal patterns and glucoprivic feeding in the guanethidine-sympathectomized, adrenodemedullated rat

The feeding behavior of rats sympathectomized by neonatal administration of guanethidine (GUA) and/or adult adrenal demedullation (MDL) was investigated. GUA treatment tended to decrease body weight gain and food intake, chiefly by decreasing meal size and increasing satiety ratios. It also attenuated the increase in food intake caused by 2-deoxy-D-glucose (2DG; 150, 300, 450 mg/kg, IP) but not by insulin (3, 6, 9 U/kg, IP). MDL altered meal patterns in the same manner as GUA treatment but the effects were of smaller magnitude. It did not influence the response to either glucoprivic challenge. Combined GUA treatment and MDL generally produced additive effects. These results suggest that the major sympathetic influence on feeding is through adrenergic innervation and not circulating catecholamines. The hypothesis that the alteration in feeding patterns produced by ventromedial hypothalamic lesions is due to decreased sympathetic activity was not supported.     

Theophylline disrupts diurnal rhythms of humoral factors with loss of meal cyclicity

To test the possibility that theophylline induced circadian disappearance of food intake might depend upon rhythmic disruption of blood glucose, insulin and free fatty acids (FFA), theophylline was administered chronically. This markedly lengthened postprandial intermeal intervals during the dark, and induced approximately identical intermeal intervals and identical meal sizes in the light and dark periods. In contrast to the clear light-dark dependent oscillations of serum glucose, insulin and FFA in the controls, the theophyllinized rats lost circadian fluctuation of each of these three chemical substances. Further, theophyllinized rats, unlike controls, had no time-dependent fluctuation in the levels of these substances at ? 120, ?60 or ?15 min preceding the onset of the first meal before the dark. These findings, together with previous reports, explain the disappearance of nocturnal feeding rhythm in theophyllinized rats in terms of functional destruction of circadian regulation in the hypothalamus which modulate the production of chemical determinants of food intake.     

Thermogenic effect of adrenaline: interaction with insulin

Summary The contribution of insulin (3.6 pmol sd kg body mass^–1·min^–1 to adrenaline-induced (0.164 nmol · kg fat free mass^–1·min^–1) thermogenesis was studied in ten postabsorptive healthy volunteers using two sequential protocols. Variables considered were oxygen consumption as well as carbon dioxide production, heart rate, blood pressure, plasma concentrations of glucose, insulin, glycerol, free fatty acids,-HO-butyrate and lactate. Adrenaline increased plasma concentrations of glucose, glycerol, free fatty acids, and-HO-butyrate, and heart rate and metabolic rate during normo-insulinaemia [61.3 (SEM 6.6) pmol·^–1]. Similar effects were observed during hyperinsulinaemia [167.9 (SEM 18.7) pmol·^–1], but the effect of adrenaline on oxygen consumption was reduced. On average, metabolic rate increased by 12.9% during normo-insulinaemia and by 8.9% during hyperinsulinaemia. We concluded that relative hyperinsulinaemia resulted in decreased adrenaline-induced thermogenesis and therefore increased whole body anabolism.     

Training effects of cross-country skiing and running on maximal aerobic cycle performance and on blood lipids

Summary Two experiments were carried out to compare the cardiorespiratory and metabolic effects of cross-country skiing and running training during two successive winters. Forty-year-old men were randomly assigned into skiing (n = 15 in study 1,n = 16 in study 2), running (n = 16 in study 1 andn = 16 in study 2) and control (n = 17 in study 1 andn = 16 in study 2) groups. Three subjects dropped out of the programme. The training lasted 9–10 weeks with 40-min exercise sessions three times each week. The training intensity was controlled at 75%–85% of the maximal oxygen consumption (VO_2max) using portable heart rate metres and the mean heart rate was 156–157 beats·min^–1 in the training groups. In the pooled data of the two studies the mean increase in theVO_2max (in ml·min^–1·kg^–1) on a cycle ergometer was 17% for the skiing group, 13% for the running group and 2% for the control group. The increase inVO_2max was highly significant in the combined exercise group compared to the control group but did not differ significantly between the skiing and running groups. The fasting serum concentrations of lipoproteins and insulin did not change significantly in any of the groups. These results suggested that training by cross-country skiing and running of the same duration and intensity at each session for 9–10 weeks improved equally the cardiorespiratory fitness of untrained middle-aged men.     

Effects of Na+, K+ and Mg2+ on45Ca2+ uptake by pancreatic islets

Microdissected pancreatic islets of noninbredob/ob-mice were used to study ionic effects on the lanthanum-nondisplaceable⁴⁵Ca²⁺ uptake by islet cells. Omission of Mg²⁺ from the incubation medium had no effect, but the⁴⁵Ca²⁺ uptake was increased by omission of Na⁺ and decreased by omission of K⁺. Excess Mg²⁺ (1.2–15 mM) inhibited and excess K⁺ (4.7–25 mM) stimulated the⁴⁵Ca²⁺ uptake in a concentration-dependent manner. Stimulation of⁴⁵Ca²⁺ uptake in Na⁺-deficient islets was associated with an enhancement of the basal insulin release. Total abolishment of glucose-stimulated⁴⁵Ca²⁺ uptake in K⁺-deficient islets did not preclude a significant secretory response to glucose. It is concluded that the lanthanum-nondisplaceable⁴⁵Ca²⁺ uptake shows a partial correlation to insulin release.