RESUMO
To examine putative relationships between adrenergic receptors on accessible circulating cells and relatively inaccessible extravascular catecholamine target tissues, we measured mononuclear leukocyte (MNL) and lung beta-adrenergic receptors and platelet and lung alpha-adrenergic receptors in tissues obtained from 15 patients undergoing pulmonary resection. Plasma catecholamine concentrations were measured concurrently to explore potential regulatory relationships between the activity of the sympathochromaffin system and both intravascular and extravascular adrenergic receptors. MNL and lung membrane beta-adrenergic receptor densities were correlated highly (r = 0.845, P less than 0.001). Platelet alpha 2-adrenergic receptor and lung alpha 1-adrenergic receptor densities were not. Lung alpha 1-adrenergic receptor densities were positively related to plasma norepinephrine (r = 0.840, P less than 0.01) and epinephrine (r = 0.860, P less than 0.01) concentrations; in contrast, lung beta-adrenergic receptor densities were not positively related to plasma catecholamine concentrations (they tended to be inversely related to plasma norepinephrine and epinephrine [r = -0.698, P less than 0.05] levels). This apparent reciprocal regulation of alpha- and beta-adrenergic receptors by the sympathochromaffin system was only demonstrable with adrenergic receptor measurements in the extravascular catecholamine target tissue. Neither MNL beta-adrenergic receptor nor platelet alpha-adrenergic receptor densities were correlated with plasma catecholamine levels. Thus, although measurements of beta-adrenergic receptors on circulating mononuclear leukocytes can be used as indices of extravascular target tissue beta-adrenergic receptor densities (at least in lung and heart), it would appear that extravascular tissues should be used to study adrenergic receptor regulation by endogenous catecholamines in humans. These data provide further support for the concept of up regulation, as well as down regulation, of some adrenergic receptor populations during short-term activation of the sympathochromaffin system in humans.
Assuntos
Plaquetas/metabolismo , Sistema Cromafim/fisiologia , Leucócitos Mononucleares/metabolismo , Pulmão/metabolismo , Receptores Adrenérgicos alfa/análise , Receptores Adrenérgicos beta/análise , Adulto , Idoso , Sistema Cromafim/metabolismo , Epinefrina/sangue , Feminino , Humanos , Pulmão/irrigação sanguínea , Masculino , Pessoa de Meia-Idade , Norepinefrina/sangue , Prazosina , Receptores Adrenérgicos alfa/fisiologia , Receptores Adrenérgicos beta/fisiologiaRESUMO
Advanced age is a risk factor for hypoglycemia caused by sulfonylureas (and insulin) used to treat diabetes mellitus. Therefore, we hypothesized that there is an age-associated impairment of glucose counterregulation and further that this is the result of a sedentary life-style. To test these hypotheses, glycemic and neuroendocrine responses to hypoglycemia, produced by 0.05 U/kg body wt insulin i.v. were measured in nondiabetic elderly subjects (age 65.1 +/- 0.9 yr n = 23)--and in a subset (n = 11) again after 1 yr of physical training (which increased VO2 max by 5.2 +/- 0.9 ml.kg-1.min-1, P less than 0.05)--and compared with these responses in nondiabetic young subjects (23.8 +/- 0.6 yr, n = 18). Recovery from hypoglycemia was attenuated (analysis of variance P less than 0.001) in the elderly (plasma glucose recovery rate 29.4 +/- 2.2 vs. 42.7 +/- 5.0 microM/min, P less than 0.02). This attenuation was the result of a smaller counterregulatory increment in glucose production (maximum increment 13.3 +/- 1.1 vs. 17.2 +/- 1.1 mumol.kg-1.min-1; P less than 0.05) rather than a greater increment in glucose utilization in the elderly. The attenuated glucose recovery was associated with higher plasma insulin concentrations (maximum increment 1385 +/- 122 vs. 940 +/- 72 pM, P less than 0.01) and reduced glucagon responses to hypoglycemia (maximum increment 43 +/- 6 vs. 66 +/- 12 ng/L). The epinephrine, norepinephrine, cortisol, and growth hormone responses were similar, although the epinephrine response was slightly delayed and the growth hormone response appeared smaller in the elderly.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Glicemia/metabolismo , Hipoglicemia/fisiopatologia , Insulina/farmacologia , Ácido 3-Hidroxibutírico , Adulto , Fatores Etários , Idoso , Alanina/sangue , Análise de Variância , Pressão Sanguínea , Peptídeo C/sangue , Epinefrina/sangue , Ácidos Graxos não Esterificados/sangue , Glucagon/sangue , Hormônio do Crescimento/sangue , Frequência Cardíaca , Humanos , Hidrocortisona/sangue , Hidroxibutiratos/sangue , Hipoglicemia/sangue , Insulina/sangue , Lactatos/sangue , Pessoa de Meia-Idade , Norepinefrina/sangueRESUMO
To determine the role of adrenal medullary hormones in controlling the rate of liver glycogenolysis during exercise, adrenodemedullated (ADM) and sham-operated (SO) rats were run on a rodent treadmill at 21 m/min up a 15% grade for 0, 30, or 60 min. Rats were anesthetized by intravenous injection of pentobarbital sodium, and liver, muscle, and blood were collected and frozen. Liver glycogen decreased at similar rates in ADM and SO rats. Hepatic adenosine 3',5'-cyclic monophosphate (cAMP), plasma glucagon, and plasma free fatty acids increased to the same extent in both ADM and SO rats. The adrenodemedullation caused a reduction in glycogenolysis in the fast-twitch white region of the quadriceps, soleus, and lateral gastrocnemius during exercise. The normal exercise-induced increase in blood glucose and lactate and the decline in plasma insulin were not observed in the demedullated rats. During submaximal exercise the principal targets for epinephrine released from the adrenal medulla appear to be pancreatic beta-cells and skeletal muscle and not the liver.
Assuntos
Epinefrina/fisiologia , Glicogênio Hepático/metabolismo , Fígado/metabolismo , Esforço Físico , Medula Suprarrenal/fisiologia , Animais , Glicemia/metabolismo , AMP Cíclico/metabolismo , Ácidos Graxos não Esterificados/sangue , Glucagon/sangue , Glicogênio/metabolismo , Insulina/sangue , Lactatos/sangue , Ácido Láctico , Masculino , Músculos/metabolismo , Ratos , Ratos Endogâmicos , Fatores de TempoRESUMO
We assessed simplified approaches to measurement of steady-state norepinephrine (NE) kinetics (short, nonprimed infusions of [3H]NE or of unlabeled NE and arterialized venous sampling), then reexamined the kinetic mechanism(s) of the age-associated increase in plasma NE, and tested the hypothesis that the latter is the result of a sedentary lifestyle. We studied 17 young (21-28 yr) and 21 elderly (60-76 yr) subjects and a subset (n = 8) of the latter again after 1 yr of physical training. NE appearance rates (Ra) and NE metabolic clearance rates (MCRs), calculated from arterialized venous data, were not significantly different from those calculated from arterial data, whereas those calculated from venous data were substantially (approximately 50%) higher. NE Ra and NE MCR, determined from infusions of unlabeled NE were approximately 20% higher than those determined with [3H]NE, a finding plausibly attributed to approximately 20% suppression of endogenous NE appearance. Arterialized venous plasma NE concentrations were significantly higher in the elderly as a result of significantly higher NE Ra and lower NE MCR. However, arterial NE Ra was not increased, and venous NE MCR was not decreased significantly in the elderly. In the subset of elderly subjects, 1 yr of physical training, which increased peak O2 consumption by 24%, did not decrease plasma NE or NE Ra or increase NE MCR. Therefore, 1) arterial sampling provides no practical advantage over arterialized venous sampling in the measurement of NE kinetics. 2) The use of unlabeled NE infusions to determine NE kinetics overestimates NE Ra and NE MCR by approximately 20%.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Envelhecimento/sangue , Norepinefrina/sangue , Educação Física e Treinamento , Adulto , Idoso , Feminino , Humanos , Cinética , Masculino , Concentração OsmolarRESUMO
This study was designed as a comparative analysis of the compressive strengths of precious versus nonprecious metals with various framework designs used in clinical restorations. One hundred thirty-five statistically uniform ceramometal restorations were fabricated. The restorations were cemented to the die and then subjected to stroke-control compression forces in an Instron loading machine. Simulated clinical failure was recorded by the Instron load cell recorder in pounds of load.
Assuntos
Coroas , Ligas Dentárias , Porcelana Dentária , Ligas de Cromo , Planejamento de Dentadura , Ligas de Ouro , Humanos , Estresse Mecânico , Propriedades de SuperfícieRESUMO
To test the hypothesis that glycemic sensitivity to epinephrine is reduced in older individuals and to assess the impact of a sedentary lifestyle on responses to the hormone, we performed 30-min sequential intravenous infusions of epinephrine (0, 41, 82, 164, 246, and 328 pmol. kg-1. min-1) in young (n = 10) and older (n = 23) healthy subjects. We performed these again after 12 mo of physical training, which raised peak O2 consumption from 24.4 +/- 1.0 to 30.4 +/- 1.4 ml. kg-1. min-1 (P < 0.01) in most of the older subjects (n = 21). During epinephrine infusions, plasma epinephrine concentrations were higher (P = 0.0001) in older than in young subjects (e.g., final values of 7,280 +/- 500 vs. 4,560 +/- 380 pmol/l, respectively), indicating that the clearance of epinephrine from the circulation was reduced in the older individuals. Plasma epinephrine concentration-response curves disclosed reduced glycemic sensitivity to the hormone in the older subjects (P = 0.0001), a finding plausibly attributed to increased sympathetic neural activity, as evidenced here by higher plasma norepinephrine concentrations (P = 0.0001) in the older subjects and consequent desensitization of cellular responsiveness to catecholamines. Training did not correct reduced epinephrine clearance, reduced glycemic sensitivity to epinephrine, or raised norepinephrine levels. We conclude that aging is associated with reduced clearance of epinephrine from the circulation and reduced glycemic sensitivity to epinephrine, the latter plausibly attributed to an age-associated increase in sympathetic neural norepinephrine release. These age-associated changes are not the result of a sedentary lifestyle.
Assuntos
Envelhecimento/fisiologia , Glicemia/metabolismo , Epinefrina/sangue , Ácido 3-Hidroxibutírico/sangue , Adulto , Idoso , Envelhecimento/sangue , Alanina/sangue , Glicemia/efeitos dos fármacos , Pressão Sanguínea/efeitos dos fármacos , Epinefrina/administração & dosagem , Epinefrina/farmacologia , Ácidos Graxos não Esterificados/sangue , Feminino , Glucagon/sangue , Frequência Cardíaca/efeitos dos fármacos , Hormônio do Crescimento Humano/sangue , Humanos , Hidrocortisona/sangue , Infusões Intravenosas , Insulina/sangue , Lactatos/sangue , Masculino , Pessoa de Meia-Idade , Norepinefrina/sangue , Resistência Física , Esforço Físico/fisiologiaRESUMO
To determine the possibility of a threshold concentration of plasma epinephrine that stimulates liver glycogenolysis during exercise, adrenodemedullated (ADM) and sham-operated (SHAM) rats were infused with saline or epinephrine at rates that produced plasma concentrations ranging between 0.01 ng/ml (0.06 nM) and 4.3 ng/ml (23.7 nM). During the infusion rats were run on a rodent treadmill for 0, 30, or 60 min at 21 m/min up a 15% grade. Liver glycogen decreased at similar rates in all exercising rats regardless of plasma epinephrine concentration. Epinephrine infusion stimulated significant muscle glycogen depletion in the soleus and red and white vastus lateralis muscles. ADM saline-infused animals exhibited the least muscle glycogen depletion. Blood glucose and lactate in exercising ADM rats increased as the epinephrine infusion concentration increased. During exercise, there was no epinephrine concentration that stimulated liver glycogenolysis more effectively than physiological saline.
Assuntos
Epinefrina/farmacologia , Glicogênio/metabolismo , Fígado/metabolismo , Músculos/metabolismo , Esforço Físico , Medula Suprarrenal/fisiologia , Adrenalectomia , Animais , Glicemia/metabolismo , Corticosterona/sangue , Epinefrina/sangue , Ácidos Graxos não Esterificados/sangue , Insulina/sangue , Lactatos/sangue , Ácido Láctico , Fígado/efeitos dos fármacos , Masculino , Músculos/efeitos dos fármacos , Ratos , Ratos EndogâmicosRESUMO
To determine the role of epinephrine in glycogenolysis during high-intensity exercise, rats were adrenodemedullated (ADM) or sham operated (SHAM) and run for either 30 min at 38 m/min or for 5 min at 27, 38, or 48 m/min up a 15% grade. At the end of exercise the rats were anesthetized by intravenous injection of pentobarbital sodium. Liver, blood, and muscle samples were obtained. Plasma epinephrine values were 5.9 and 0.3 nM for SHAM and ADM animals, respectively, after 30 min of exercise. Liver glycogen decreased by 16 and 21 mg/g in the SHAM and ADM groups, respectively, and liver cAMP increased significantly in both groups. Glycogen in the soleus muscle decreased 80% in the SHAM but only 43% in the ADM animals after 30 min of exercise. The exercise-induced hyperglycemia observed in the SHAM animals was not present in the ADM animals. The responses of cyclic AMP, soleus glycogen, and blood glucose were similar in both the 5- and 30-min exercise groups. During intense exercise, epinephrine is unessential for stimulating liver glycogenolysis but does play an important role in stimulating glycogenolysis in the soleus muscle and in establishing exercise-induced hyperglycemia.
Assuntos
Medula Suprarrenal/fisiologia , Glicogênio/metabolismo , Esforço Físico , Animais , Glicemia/análise , Epinefrina/sangue , Glucagon/sangue , Fígado/metabolismo , Masculino , Músculos/metabolismo , Norepinefrina/sangue , Ratos , Ratos Endogâmicos , Fatores de TempoRESUMO
To assess the role of catecholamines in the prevention of hypoglycemia during moderate exercise (approximately 60% peak O2 consumption for 60 min), normal humans were studied with combined alpha- and beta-adrenergic blockade and with adrenergic blockade while changes in insulin and glucagon were prevented with the islet clamp technique (somatostatin infusion with insulin and glucagon infused at fixed rates). The results were compared with those from an islet clamp alone study. In contrast to a comparison study (saline infusion), adrenergic blockade resulted in a small initial decrease in plasma glucose during exercise, from 5.0 +/- 0.2 to 4.4 +/- 0.2 mmol/l (P less than 0.01), but the level then plateaued. There was a substantial exercise-associated decrement in plasma glucose when insulin and glucagon were held constant, i.e., from 5.5 +/- 0.2 to 3.4 +/- 0.2 mmol/l (P less than 0.0001), but the level again plateaued. However, when insulin and glucagon were held constant and catecholamine actions were blocked simultaneously, progressive hypoglycemia, to 2.6 +/- 0.6 mmol/l (P less than 0.001), developed during exercise. Hypoglycemia was the result of an absent increase in glucose production and an exaggerated initial increase in glucose utilization. Thus we conclude that sympathochromaffin activation plays a minor role when insulin and glucagon are operative, but a catecholamine, probably epinephrine, becomes critical to the prevention of hypoglycemia during exercise when changes in insulin and glucagon do not occur.
Assuntos
Glicemia/metabolismo , Glucagon/sangue , Hipoglicemia/prevenção & controle , Insulina/sangue , Fentolamina/farmacologia , Esforço Físico , Propranolol/farmacologia , Somatostatina/farmacologia , Ácido 3-Hidroxibutírico , Adulto , Pressão Sanguínea/efeitos dos fármacos , Peptídeo C/sangue , Epinefrina/sangue , Ácidos Graxos não Esterificados/sangue , Glucagon/administração & dosagem , Glucagon/farmacologia , Hormônio do Crescimento/sangue , Frequência Cardíaca/efeitos dos fármacos , Humanos , Hidrocortisona/sangue , Hidroxibutiratos/sangue , Hipoglicemia/etiologia , Infusões Intravenosas , Insulina/administração & dosagem , Insulina/farmacologia , Cinética , Masculino , Fentolamina/administração & dosagem , Propranolol/administração & dosagem , Valores de Referência , Somatostatina/administração & dosagem , Fatores de TempoRESUMO
The sympathochromaffin system, probably sympathetic neural norepinephrine, plays a primary role in the prevention of hypoglycemia during exercise in humans. Our previous data indicated that changes in pancreatic islet hormones are not normally critical but decrements in insulin, increments in glucagon, or both become critical when catecholamine actions are blocked pharmacologically. To distinguish between the role of insulin and that of glucagon in this secondary line of defense against hypoglycemia during exercise in humans, glucoregulation during moderate exercise (approximately 55% of maximum O2 consumption over 60 min) was studied in people who could not decrease insulin but could increase glucagon, i.e., patients with insulin-dependent diabetes mellitus (IDDM). While receiving constant intravenous infusions of regular insulin, in individualized doses shown to result in stable plasma glucose concentrations of approximately 95 mg/dl before exercise, patients with IDDM were studied under two conditions: 1) a control study (n = 13) and 2) an adrenergic blockade study (propranolol infusion, n = 8). In the control study, mean plasma glucose concentrations did not change (from 95 +/- 2 to 100 +/- 11 mg/dl) during exercise despite constant plasma free insulin levels. In the adrenergic blockade study plasma glucose declined (from 96 +/- 2 to 74 +/- 7 mg/dl, P less than 0.01) but stabilized; hypoglycemia did not occur. Exercise-associated increments in plasma glucagon were comparable in the two studies. These data confirm that decrements in insulin are not critical to the prevention of hypoglycemia during moderate exercise in humans and indicate that compensation for deficient catecholamine action does not require decrements in insulin.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Glicemia/metabolismo , Diabetes Mellitus Tipo 1/metabolismo , Glucagon/fisiologia , Insulina/fisiologia , Esforço Físico , Ácido 3-Hidroxibutírico , Adulto , Alanina/sangue , Pressão Sanguínea , Epinefrina/sangue , Ácidos Graxos não Esterificados/sangue , Feminino , Glicerol/sangue , Hormônio do Crescimento/sangue , Frequência Cardíaca , Humanos , Hidrocortisona/sangue , Hidroxibutiratos/sangue , Lactatos/sangue , Masculino , Norepinefrina/sangue , Consumo de OxigênioRESUMO
To assess the roles of decrements in insulin and increments in glucagon in the prevention of hypoglycemia during moderate exercise (approximately 60% peak O2 consumption for 60 min), normal young men were studied during somatostatin infusions with insulin and glucagon infused to 1) hold insulin and glucagon levels constant, 2) decrease insulin, 3) increase glucagon, and 4) decrease insulin and increase glucagon during exercise. In contrast to a comparison study (saline infusion), when insulin and glucagon were held constant, glucose production did not increase and plasma glucose decreased from 5.5 +/- 0.2 to 3.4 +/- 0.2 mmol/l (P less than 0.001) initially during exercise. Notably, plasma glucose then plateaued and was 3.3 +/- 0.2 mmol/l at the end of exercise. This decrease was at most only delayed when either insulin was decreased or glucagon was increased independently. However, when insulin was decreased and glucagon was increased simultaneously, there was an initial increase in glucose production, and the glucose level was 4.5 +/- 0.2 mmol/l at 60 min, a value not different from that in the comparison study. Thus we conclude that both decrements in insulin and increments in glucagon play important roles in the prevention of hypoglycemia during exercise and do so by signaling increments in glucose production. However, since hypoglycemia did not develop during exercise when changes in insulin and glucagon were prevented, an additional counterregulatory factor, such as epinephrine, must be involved in the prevention of hypoglycemia during exercise, at least when the primary factors, insulin and glucagon, are inoperative.