Metabolic and hormonal effects of muscular exercise in juvenile type diabetics

Summary Metabolic and hormonal effects of muscular exercise were studied in juvenile-type diabetics in relation to the prevailing degree of metabolic control and compared with those in healthy control subjects. Two groups of diabetic patients, one in moderate metabolic control and one in ketosis due to insulin withdrawal, were subjected to a 3 hour bicycle ergometer test of comparable, mild work intensity. In both groups of diabetics the exercise-induced rise in blood lactate was similar, but was significantly higher than in control subjects. Blood alanine levels showed a transient, significant rise in both diabetic groups, but not in controls. Blood concentrations of branch-chained amino acids remained unchanged. In the moderately controlled diabetics, exercise induced a marked fall of blood glucose and increases in blood levels of free fatty acids (FFA), ketone bodies and glucagon, which were comparable to the exercise effects in normal controls. In ketotic diabetics, however, exercise led to an additional rise in blood glucose concentration and to increases in ketone body, glucagon and cortisol levels. Significant correlations were found between the exercise effect on blood glucose and initial blood levels of glucose, FFA, ketone bodies and branch chained amino acids: pre-exercise values of above 325 mg/dl glucose, 1173 mol/l FFA, 2.13 mmol/l ketone bodies and 0.74 mmol/l branch chained amino acids led to increased blood glucose levels on exercise, whereas below these limits glucose fell during the exercise test. These findings seem to be, at least in part, explained by the hypothesis of a permissive effect of insulin during stimulation of muscle glucose uptake by exercise. The increased circulating levels of glucagon and cortisol during exercise in ketotic diabetics might represent additional hyperglycaemic and, probably more important, lipolytic and ketogenic stimuli. The results suggest that in moderately controlled, non-ketotic diabetics blood glucose falls during exercise; in ketotic, relatively insulin deficient patients, muscular activity has adverse metabolic and hormonal effects: a further increase in blood glucose, plasma glucagon and cortisol and a rapid aggravation of ketosis.     

烧伤合并吸入性肺损伤患者应用间歇性有氧运动和交互式训练的临床研究

目的 探讨间歇有氧运动联合交互式训练模式对烧伤合并吸入性肺损伤患者的疗效.方法 选择2018年5月至2019年6月我院接受康复治疗的烧伤并吸入性肺损伤患者80例,随机平均分为观察组和对照组;观察组采用间歇有氧运动联合交互式训练模式进行康复,对照组仅采用交互式训练模式进行康复;3个月后比较两组患者肺功能、运动心肺功能、肌...     

Effect of beta-adrenergic blockade on circulating catecholamines and dopamine-beta-hydroxylase activity during exercise in normal subjects

We investigated the effects of beta-adrenergic blockade with propranolol (P) on circulating catecholamines at rest and during isometric and dynamic exercise. By means of a radioenzymatic assay, we measured plasma norepinephrine (NE) and epinephrine (E) concentrations in nine normal, sedentary men, aged 22 to 34 years. Measurements were made during resting conditions, at 3 minutes of 30% maximal isometric handgrip exercise (IHE), and during submaximal and maximal dynamic treadmill exercise. Measurements were repeated one week later after the subjects received P in doses ranging from 40 to 80 mg four times a day (plasma P levels at the time of exercise ranged from 96 to 303 ng/ml with a mean of 178 ng/ml). We also measured serum dopamine-beta-hydroxylase (DBH) activity to detect changes in chronic sympathetic tone. Changes in NE from rest to exercise were significant (p less than 0.01) at all exercise loads with or without P. Changes in E from rest to exercise were significant (p less than 0.01) at all exercise loads with or without P except for submaximal dynamic exercise during the control study (p greater than 0.05). For NE, there were no significant differences between the control and P values either at rest or during any form of exercise. For E, there were no significant changes between the control and p values at rest or at maximal dynamic exercise, although there were mild increases (p less than 0.05) with IHE and submaximal dynamic exercise. DBH activity increased significantly (p less than 0.01) from rest to exercise for all exercise points with and without P, but there were no significant differences between the control and p values either at rest or during any form of exercise. In conclusion, we have demonstrated that competitive blockade of beta-adrenergic receptors at the tissue level does not alter neural release of NE or DBH and has little effect on adrenal release of E.     

Effect of beta-adrenergic blockade on biochemical and metabolic response to exercise

During normal exercise the myocardium, skeletal muscle, liver and adipose tissue all participate in the metabolic response to exercise. Beta-blockade, by impairing this biochemical-metabolic response at several levels, limits the capacity for maximal exercise. The relevant effects of beta blockade may include hypoglycemia, impaired mobilization of free fatty acids and decreased breakdown of glycogen in skeletal muscle. The organs responsible for these metabolic changes are the liver (blood sugar), adipose tissue (blood free fatty acids) and skeletal muscle. Most of the metabolic beta-adrenergic receptors are thought to be beta 2 in nature. Two populations of receptors (mixed beta 1 and beta 2) may explain some controversial findings. Overall, the data suggest that cardioselective agents may have less effect than nonselective agents in producing metabolic impairment during sustained exercise.     

Effects of Metoprolol on the Counter-regulation and Recognition of Prolonged Hypoglycemia in Insulin-dependent Diabetics

ABSTRACT. The effect of metoprolol on the counter-regulation of prolonged hypoglycemia was studied in eight insulin-dependent diabetics. Insulin was given as an i.v. infusion of 2.4 U/h over 180 min alone, or together with metoprolol (3.0 mg i.v. bolus followed by an i.v. infusion of 4.8 mg/h) in random order. Blood glucose, counter-regulatory hormones, hypoglycemic symptoms and the cardiovascular responses were assayed over 240 min. Metoprolol did not significantly modify the blood glucose levels. The plasma levels of free insulin, however, were elevated by approximately 20% (p<0.01) by metoprolol during hypoglycemia and the plasma concentrations of epinephrine, norepinephrine, growth hormone and cortisol were enhanced by the drug. Sweating was increased by metoprolol, while other symptoms were unaltered. We conclude that metoprolol administered acutely does not aggravate prolonged hypoglycemia in diabetics with blunted response of glucagon. Moreover, exaggerated responses of counter-regulatory hormones, provoked by metoprolol, may compensate for the inhibitory effect of this drug on insulin clearance.     

低强度间歇性运动对大鼠血脂和胰岛素抵抗指数的影响

目的探讨低强度间歇性运动对SD大鼠脂联素、总胆固醇(TC)、甘油三酯(TG)和胰岛素抵抗指数(IR I)的影响。方法 20只SD大鼠随机分为2组:对照组(C),低强度间歇性运动组(F),每组6只,训练6 w;采用Bedford训练方案,低强度间歇性运动组每天9~10次10 s跑台运动,间歇时间30~60 s,最大强度相当于75%VO2m ax;末次训练后24 h各组大鼠安静状态下处死,左心室抽取血液。采用比色法和ELISA法分别测定大鼠脂联素、TC、TG和胰岛素水平。结果 F组脂联素水平与C组没有显著差异(P>0.05);F组TG水平与C组相比显著降低(P<0.05);F组TC水平与C组相比非常显著降低(P<0.01);F组IR I与C组没有显著差异(P>0.05)。结论低强度间歇性运动对预防胰岛素抵抗和糖尿病等代谢性疾病的发生具有一定积极意义。     

Growth hormone-releasing hormone and growth hormone secretagogue-receptor ligands: focus on reproductive system

Growth hormone-releasing hormone (GHRH) and somatostatin are the most important hypothalamic neurohormones controlling growth hormone (GH) secretion. Several neurotransmitters and neuropeptides also play an important role in the control of GH secretion, mainly acting via modulation of GHRH and somatostatin. In the past two decades, particular attention has been given to a new family of substances showing a strong GH-releasing effect: GH secretagogues (GHSs). GHSs increase GH secretion in a dose-and age-related manner after iv and even oral administration. The endocrine effects of GHSs, are not fully specific for GH; they show, in fact, prolactin- (PRL), adenocorticotropic hormone- and cortisol-releasing effects. Specific GHS receptors are present in both the central nervous system and peripheral tissues, where they mediate several extraendocrine effects of GHSs. The isolation of these “orphan” receptors suggested the existence of an endogenous GHS-like ligand that could be represented by a recently discovered gastric peptide, named ghrelin. The interaction between GHSs and GHRH at the central level and in the pituitary gland, but not at peripheral level, has clearly been shown. Because GHRH and GHS receptors share the same localization in some peripheral tissues, they may have some interactions even at this level.     

Hypothalamic catecholamine biosynthesis and pituitary gonadotropin secretion in vitro: Effect of hyperprolactinemia

The effect of hyperprolactinemia on central catecholamine biosynthesis and anterior pituitary hormone release was studied using an in vitro methodology. The incorporation of [³H]tyrosine into hypothalamic and neurohypophyseal catecholamines was determined using a new method which combines high performance liquid chromatography (HPLC) with amperometric detection (LCEC). Elevated plasma prolactin levels, induced by pituitary transplants, resulted in increased in vitro biosynthesis of medial basal hypothalamic (MBH) dopamine (DA), but not norepinephrine (NE). Neurohypophyseal DA biosynthesis (including the intermediate lobe) was not affected. Plasma LH levels were depressed by hyperprolactinemia although the content of hypothalamic luteinizing hormone-releasing hormone (LHRH) was not changed. In parallel studies, the anterior pituitaries from these animals were incubated in vitro using a paired-half technique and LH and PRL release measured. While the basal release of prolactin was not altered by hyperprolactinemia, LH release was significantly decreased. Gonadotroph responsiveness to LHRH was significantly increased, while the inhibition of prolactin by dopamine was not altered. There was a decrease in pituitary prolactin content with normal LH levels. These experiments confirm several in vivo reports which show that hypothalamic dopaminergic but not noradrenergic activity is increased by prolactin. This action is specifically localized in the tuberoinfundibular dopaminergic neurons. Furthermore, these experiments suggest that these central changes result in alterations in both gonadotroph and mammotroph function.     

Effect of beta-adrenergic receptors blockade on auricular natriuretic factor, aldosterone and renine blood activity during physical exercise

Physical exercise stimulates the renin-angiotensin-aldosterone system. However several factors affect the control of mineralocorticoid secretion. In this study, eight healthy volunteers performed maximal exercise on cycle ergometer after being pretreated for 3 days with placebo (P) or with a non selective beta-blocker (B) (pindolol 15 mg/day). Plasma reinin activity (PRA), aldosterone (ALD), atrial natriuretic factor (ANF), and kalemia (K+) were measured at rest (R) and during exercise until exhaustion (E). (table; see text) These results confirm the role of beta-adrenoceptor activation in the increased PRA during exercise. It appears an exercise-induced increase in plasma ANF which was more elevated in subjects treated with pindolol, but which had no inhibitory effect on ALD secretion in theses conditions. K+ rose during exercise and this hyperkalemia tended to be higher with a beta-blocker. It is suggested that K+ elevation counterbalance both PRA decrease and ANF increase to be responsible for the absence of change in plasma ALD during beta-blockade.     

Comparison of continuous infusion and intermittent boluses of furosemide in acute heart failure: A protocol for systematic review and meta-analysis

Background:Acute heart failure (HF) is a common cause of hospital admission. This study aims to compare continuous infusion and intermittent boluses of furosemide in treating acute HF.Methods:This protocol of systematic review and meta-analysis has been drafted under the guidance of the preferred reporting items for systematic reviews and meta-analyses protocols. Electronic databases including Web of Science, Embase, PubMed, Wanfang, Data, Scopus, Science Direct, and Cochrane Library will be searched in June 2021 by 2 independent reviewers. The main outcomes are post-treatment daily urine output, weight, length of stay, serum sodium, potassium, and creatinine. Two researchers conducted a quality assessment in strict accordance with the risk bias assessment tool recommended by the Cochrane Handbook Version5.3. We performed the meta-analysis by Stata version 10.0 software.Results:The results of this systematic review and meta-analysis will be published in a peer-reviewed journal.Conclusion:The choice of furosemide regime in acute HF remains physician preference. Both bolus and continuous infusion yields satisfactory outcomes.     

Effect of somatostatin on metabolic and hormonal changes induced by nicotinic acid in insulin-dependent diabetics

Summary The study investigated the respective influences of nicotinic acid and somatostatin on plasma concentrations of blood glucose, free fatty acids, glucagon, growth hormone and cortisol in insulin-dependent diabetic subjects. After administration of nicotinic acid alone, marked depression of plasma FFA was accompanied by significant increases of plasma glucagon, growth hormone and cortisol. The glucagon and growth hormone responses to nicotinic acid were significantly reduced when plasma FFA were raised by intravenous administration of heparin and triglycerides. Somatostatin alone induced a significant decrease in blood glucose, plasma glucagon and growth hormone concentrations. Plasma FFA remained unchanged. Somatostatin did not modify the nicotinic acid-induced fall in plasma FFA, but completely blocked the corresponding increments in glucagon and growth hormone. The cortisol rise was not altered by somatostatin. Rebound of glucagon and growth hormone levels were seen upon discontinuation of the somatostatin administration. These results demonstrate that the plasma FFA concentration plays a role in the regulation of glucagon and growth hormone secretion in insulin-dependent diabetics. Furthermore, they indicate that somatostatin, previously shown to be capable of negating the stimulatory effect of various factors on glucagon and growth hormone secretion, also affects the response of these hormones to FFA depression.Presented at the 11th Annual Meeting of the European Association for the Study of Diabetes, Munich, Sept. 1975, and published in abstract form in Diabetologia, 1975,11, 360.     

Effect of beta-adrenergic blockade with timolol on myocardial blood flow during exercise after myocardial infarction in the dog

The effect of beta-adrenergic blockade with timolol (40 micrograms/kg) on myocardial blood flow during rest and graded treadmill exercise was assessed in 12 chronically instrumented dogs 10 to 14 days after myocardial infarction was produced by acute left circumflex coronary artery occlusion. During exercise at comparable external work loads, the heart rate-systolic blood pressure product was significantly decreased after timilol, with concomitant reductions of myocardial blood flow in normal, border and central ischemic areas (p less than 0.001) and increases in subendocardial/subepicardial blood flow ratios (p less than 0.05). In addition to the blunted chronotropic response to exercise, timolol exerted an effect on myocardial blood flow that was not explained by changes in heart rate or blood pressure. At comparable rate-pressure products during exercise, total myocardial blood flow was 24% lower after timolol (p less than 0.02) and flow was redistributed from subepicardium to subendocardium in all myocardial regions. Thus, timolol altered myocardial blood flow during exercise by two separate mechanisms: a negative chronotropic effect, and a significant selective reduction of subepicardial perfusion independent of changes in heart rate or blood pressure with transmural redistribution of flow toward the subendocardium.