Biomedical subjects

A B Steffens

Publications and source records attributed to A B Steffens.

At least 55 records · Page 3Linked to original sources

PubMed1990

The effect of epinephrine on oxygen consumption, overall energy metabolism, and substrate utilization in rats.

In this study the influence of epinephrine (E) on oxygen consumption, overall energy metabolism, and substrate utilization in rats has been investigated. Therefore E was infused at rates of 20, 35, and 50 ng/min for 40 min. Infusion of the solvent, saline, served as control experiment. Before, during, and after the infusion, VO2, as parameter for total metabolism, and RQ, as parameter for substrate utilization, were determined using an open circuit. In addition blood samples were taken for determination of blood glucose, plasma free fatty acids (EFA) and plasma insulin concentrations. The results show a rise in VO2 and blood glucose during infusion of E. Plasma FFA concentrations were elevated during infusion of E and of saline. Plasma insulin decreased when E was administered. RQ values were increased when E was infused at rates of 35 and 50 ng/min. The results suggest that E can influence the ratio in which glucose and FFA are utilized. This influence seems to be excerpted indirectly by influencing the availability of the substrates, rather than directly, by influencing utilization.

Animals↗

PubMed1990

Central and peripheral control of sympathoadrenal activity and energy metabolism in rats.

The role of adrenoceptors in the hypothalamus and the peripheral sympathetic nervous system in the regulation of sympathoadrenal activity and glucose and FFA mobilization was investigated in exercising rats. Apparent close relations within the two parts of the sympathoadrenal system and between factors that regulate glucose and FFA mobilization during exercise were completely disrupted by local hypothalamic infusions of adrenoceptor antagonists or anesthetic drugs. The experiments actually identified specific areas in the hypothalamus that integrate the information regarding the substrate levels in the blood with the "central command" from higher centers in the brain. Furthermore, the results of experiments with exercising intact and adrenodemedullated (Adm) rats, with and without administration of selective adrenoceptor agonists and antagonists, suggest that the activity of the sympathetic nervous system is also regulated at the level of the peripheral sympathetic nerve endings. In particular, presynaptic adrenergic regulatory mechanisms can markedly influence the outflow of NE from the sympathetic nerve endings. In conclusion, the data show that an organ-specific organization of sympathetic output during exercise may take place at different levels within the sympathetic nervous system.

Adrenal Glands↗

PubMed1990

Neuroendocrine mechanisms involved in regulation of body weight, food intake and metabolism.

Body weight regulation is the result of food intake and energy expenditure. The central nervous system (CNS), and in particular, the hypothalamus, controls food intake as well as metabolism, the latter mainly by autonomic effects on the islet of Langerhans, hepatocytes and adipocytes. Body weight, more precisely body fat content, is probably controlled by a feedback mechanism in which insulin, released from the B cell of the islet of Langerhans, plays a key role. The islet of Langerhans is an intricate neuroendocrine unit in which the release of glucagon, insulin, and somatostatin from A, B, and D cells, respectively, is controlled by the CNS via a rich autonomic innervation. In addition, the endocrine cells of the pancreas influence each other by paracrine actions. The CNS control of the islets shapes the plasma insulin and blood glucose profiles during the circadian cycle and thereby regulates the nutrient flow to the different tissues in the body. Thus, the CNS structures involved in regulation of body weight and food intake control also metabolism. The mechanisms contributing to match food intake and the needs of metabolism are discussed.

Animals↗

PubMed1990

Hypothalamic adrenoceptors mediate sympathoadrenal activity in exercising rats.

The role of hypothalamic adrenoceptors in the exercise-induced alterations of plasma norepinephrine (NE), epinephrine (E), and corticosterone concentrations was investigated in rats. Exercise consisted of strenuous swimming against a counter-current for 15 min. Before, during, and after swimming, blood samples were withdrawn through a permanent heart catheter for determination of E, NE, and corticosterone. In control rats E, NE, and corticosterone levels were all increased during exercise. Infusion of the alpha-adrenoceptor antagonist phentolamine through permanent bilateral cannulas into the ventromedial hypothalamus (VMH) immediately before exercise reduced the exercise-induced increase in plasma E without affecting NE. Infusion of the beta-adrenoceptor antagonist timolol into the VMH enhanced plasma E and attenuated plasma NE increases. Infusion of phentolamine into the lateral hypothalamic area (LHA) led to enhanced NE and unchanged E concentrations, whereas infusion of timolol into the LHA caused a potentiation of the increase in plasma E without an effect on NE. Plasma corticosterone concentrations were not affected. The results suggest that 1) alpha- and beta-adrenoceptors in the hypothalamus influence peripheral catecholamine release, and 2) E and NE responses to exercise can be dissociated by interference of the central nervous system.

Adrenal Glands↗

PubMed1990

Paraventricular hypothalamic adrenoceptors and energy metabolism in exercising rats.

The role of adrenoceptors in the paraventricular nucleus (PVN) in the exercise-induced changes in plasma norepinephrine (NE), epinephrine (E), corticosterone, free fatty acids (FFA), and blood glucose was investigated in rats. Exercise consisted of strenuous swimming against a countercurrent for 15 min. Before, during, and after swimming, blood samples were withdrawn through a permanent heart catheter for determination of E, NE, corticosterone, FFA, and glucose, In control rats receiving artificial cerebrospinal fluid through permanent bilateral cannulas into the PVN, the levels of all blood components increased during exercise. Infusion of the alpha-adrenoceptor antagonist phentolamine into the PVN completely reduced the exercise-induced increases in blood glucose and plasma corticosterone concentrations. Plasma NE, E, and FFA were not affected. Infusion of the beta-adrenoceptor antagonist timolol into the PVN reduced blood glucose and plasma NE concentrations. Plasma E, corticosterone, and FFA remained unchanged. It is concluded that alpha- and beta-adrenergic receptors in the PVN are involved in the central nervous regulation of blood glucose levels during exercise, partly by influencing sympathetic outflow. alpha-Adrenoceptors in the PVN play an important role in the release of corticosterone during exercise.

Animals↗

PubMed1990

Effects of stress and exercise on rat hippocampus and striatum extracellular lactate.

Extracellular lactate was continuously monitored (lactography) to determine the effect of various stressors to assess glucose metabolism in the rat hippocampus and striatum. It appeared that immobilization, emotional stress, and exercise (physiological stress) all resulted in an increase in hippocampal extracellular lactate. Exercise had the most pronounced effect. These increases were different for rats raised in different laboratories. Only during exercise a transient increase in lactate was seen in striatum. Peripheral infusions of epinephrine and/or corticosterone did not affect the basal levels of hippocampal lactate. Adrenodemedullated rats showed an attenuated lactate increase compared with control rats during and shortly after exercise. Administration of ipsapirone, an anxiolytic drug, attenuated the stress-induced formation of the hippocampal lactate. The present study demonstrates the usefulness of lactography to monitor regional brain metabolism in freely moving animals, exposed to various stressors, breeding conditions, or drugs. The observed different responsiveness of the two brain-region studies emphasizes the different involvement of the striatum and hippocampus in motor and emotional behavior, respectively. Lactate formation is stimulated by excitatory neuronal activity, presumably originating in the cerebral cortex, although adrenal hormones appear to contribute.

Adrenal Medulla↗

PubMed1990

Biphasic insulin secretion after intravenous but not after intraportal CCK-8 infusion in rats.

The effects of physiological doses of sulfated cholecystokinin-8 (CCK-8) on insulin secretion were investigated in unrestrained unanesthetized rats. The routes of administration were intravenous or intraportal infusion. Intravenous infusion (0.33-5.0 micrograms CCK-8.kg-1.20 min-1) resulted in a biphasic response pattern consisting of a fast 1st-min rise in plasma insulin concentration and a slower second phase that lasted throughout the infusion. The first phase showed the same amplitude with all amounts of CCK-8 administered in this study, whereas the second phase exhibited dose dependency. Blood glucose levels were lowered during all infusions of CCK-8, although the second phase of insulin release was absent with the lowest dose. These results suggest a strong stimulatory effect of CCK-8 on the pancreatic beta-cells, probably by changing the set point for glucose. The described effects of intravenous administration of CCK-8 cannot be produced when the infusion is given into the portal vein. Only very high concentrations of CCK-8 (15 micrograms.kg-1.20 min-1) produced a small increase in plasma insulin levels, indicating a strong CCK-8-eliminating mechanism in the liver. These results indicate that 1) CCK-8 evokes biphasic insulin release and a concomitant drop in glucose levels, and 2) CCK-8 acting on the beta-cell in vivo is not of intestinal origin but is probably released by the pancreatic vagal branch.

Animals↗

PubMed1989

Glucose and insulin responses during mixed meals or infusion of glucose in pregnant and lactating rats.

We studied the glucose tolerance in freely moving rats throughout pregnancy and lactation and during the first week after weaning. Dioestrous virgin rats served as controls. Basal glucose and insulin levels were determined after a 2-hr fasting period. Subsequently, the changes of the insulin and the glucose levels were determined during ingestion of a mixed ad lib meal or a 2 g mixed test meal, or during infusion of glucose (7.4 mg/min for 20 min) into the vena cava. Basal glucose levels were high during early pregnancy, low during late pregnancy, and in the normal range throughout lactation and after weaning. Basal insulin levels were decreased at the end of lactation. The results of the ad lib meal and test meal experiments were essentially the same. Glucose tolerance during meals was somewhat decreased early in pregnancy. The corresponding insulin responses greatly increased during the last week of pregnancy. Glucose tolerance during IV infusion of glucose was normal during pregnancy, but increased during lactation. Insulin responses to the infusion were increased during pregnancy and decreased during lactation. We concluded that glucose tolerance is hardly affected by pregnancy and even increases in the course of lactation. This is effected by an increased responsiveness of the B-cells to glucose during late pregnancy and by an increased turnover of glucose during lactation. We discuss to what extent the actions of progesterone, placental lactogen and prolactin may explain these adaptions of maternal metabolism.

Animals↗

PubMed1989

Adrenal and sympathetic catecholamines in exercising rats.

The effects of adrenodemedullation and/or adrenoceptor agonists and antagonists on plasma epinephrine (E) and norepinephrine (NE) concentrations during exercise were investigated in rats. Exercise consisted of strenuous swimming against a countercurrent for 15 min in a pool with water of 33 degrees C. Before, during, and after swimming, blood samples were taken through a permanent heart catheter. E was not detectable in plasma of adrenodemedullated (Adm) rats. A marked reduction in the normal exercise-induced increase in plasma NE concentrations occurred in both Adm rats as well as in intact rats injected with the beta 2-selective adrenoceptor antagonist ICI 118551. Intravenous infusion of either E or the beta 2-selective agonist fenoterol restored the increase in plasma NE in Adm rats. Injection of the alpha 2-selective antagonist yohimbine in combination with infusion of the beta 2-selective agonist fenoterol into Adm rats caused an enormous increase in plasma NE. It is concluded that all NE in plasma as released during exercise originates from the peripheral nerve endings of the sympathetic nervous system. Adrenal E influences the release of NE via activation of presynaptic beta 2-adrenoceptors.

Adrenal Medulla↗

PubMed1989

Sympathoadrenal influence on glucose, FFA, and insulin levels in exercising rats.

The effects of sympathoadrenal manipulations on the exercise-induced alterations in blood glucose, plasma free fatty acids (FFA), and insulin were investigated in intact and adrenodemedullated rats. Exercise consisted of strenuous swimming against a countercurrent for 15 min. Before, during, and after swimming, blood samples were taken through a permanent heart catheter. Adrenodemedullation (Adm) markedly reduced the exercise-induced increase in both glucose and FFA. This effect was counteracted by intravenous infusion of epinephrine (E, 20 ng/min). Intravenous infusion of 50 ng E/min into Adm rats caused an exaggerated increase in glucose. In two additional experiments 1) specific adrenoceptor agonists and antagonists were administered to exercising intact and Adm rats, and 2) E or norepinephrine (NE; 20 ng/min) was infused into intact resting rats. The results suggest that E from the adrenal medulla directly affects glucose and insulin but not FFA concentrations in the blood. NE released from peripheral sympathetic nerve endings probably acts in two different ways: as neurotransmitter on liver and pancreas and as a hormone on adipose tissue.

Adrenal Medulla↗

PubMed1989

Experience affects exercise-induced changes in catecholamines, glucose, and FFA.

The interference of the experimental conditions on the exercise-induced alterations in plasma catecholamines, plasma free fatty acids, and glucose and insulin concentrations was investigated in rats. Exercise consisted of strenuous swimming against a countercurrent (0.22 m/s) for 15 min in a pool with water of 33 degrees C. Before, during, and after swimming, blood samples were taken through a permanent heart catheter. The blood component levels in rats that were confronted with exercise for the very first time were compared with the levels in rats that were well accustomed to the exercise conditions. The very first time rats swam caused an enhanced release of epinephrine from the adrenal medulla and a reduced output of norepinephrine from the sympathetic nerve endings. Furthermore, in the first time swim group, blood glucose levels were higher and plasma free fatty acid concentrations were lower compared with the well-accustomed animals. There were no differences in plasma insulin concentrations. It is concluded that the experimental conditions may interfere considerably with the hormonal and metabolic response to exercise. Furthermore the results reinforce the idea that the two parts of the sympathoadrenal system are functionally and metabolically dissociated.

Animals↗

PubMed1989

Ventromedial hypothalamic regulation of hormonal and metabolic responses to exercise.

Recent studies have indicated a neural regulation of hormonal and metabolic responses to exercise. Studies on the ventromedial hypothalamus (VMH) suggest that the VMH might be involved in neural control of exercise metabolism. We therefore studied 25 rats with or without Marcain-anesthetized VMH (Marcain and control rats, respectively) at rest or during treadmill running (26 m/min). The rats had cannulas aimed bilaterally at the VMH and chronic catheters in the left jugular vein and right carotid artery. At rest, glucose turnover and plasma concentrations of glucose, lactate, glycerol, epinephrine, norepinephrine, insulin, and corticosterone remained stable in control rats, whereas in Marcain rats these parameters, except for unchanged insulin and glucose utilization, increased after Marcain administration along with increases in hepatic and muscular glycogenolysis. During exercise, glucose turnover, hepatic and muscular glycogenolysis, and plasma concentrations of glucose, lactate, glycerol, catecholamines, and corticosterone increased, and insulin decreased in both Marcain and control rats. However, during exercise, initial hepatic glucose production, plasma catecholamines, and subsequent plasma glucose concentrations and overall hepatic glycogenolysis were lower in Marcain compared with control rats. In conclusion, glucose mobilization is enhanced by the VMH during exercise. The results suggest that decreased and increased activity in sympathetic inhibitory and facilitating VMH areas, respectively, are involved in the VMH's response to exercise.

Animals↗

PubMed1988

Structural characteristics of endogenous sugar acids and relations to feeding modulation.

Structural specificity among short-chain organic acids for effects on feeding behavior, blood glucose and insulin was investigated by infusion of 1 exogenous and 6 endogenous derivatives into the rat third cerebral ventricle. Glyceric acid (GEA) (1.0 mumol), 3,4-dihydroxybutanoic acid gamma-lactone (3,4-DB) and 3,4,5-trihydroxypentanoic acid gamma-lactone (3,4,5-TP) (2.50 mumol) decreased food intake for, at most, 24 h. These acids depressed the size of the first meal after infusion, but did not affect latency to the first meal, eating speed, drinking or ambulation. Infusion of 2,4-dihydroxybutanoic acid gamma-lactone (2,4-DB) (1.25 mumol), 2,4,5-trihydroxypentanoic acid gamma-lactone (2,4,5-TP), and an exogenous compound, 2,4,5,6-tetrahydroxyhexanoic acid gamma-lactone (2,4,5,6-TH) (2.50 mumol), induced transient initial feeding which was not necessarily accompanied by periprandial drinking. Ambulation was concomitantly increased. Of these organic acids, 3,4-DB and 2,4,5-TP were most potent in their effects on feeding. Hyperglycemia was induced by 2.50 mumol 3,4-DB leaving insulin unaffected; 2.50 mumol 2,4,5-TP caused hypoglycemia, with a persistent but not significant rise in insulin. The results suggest that slight structural differences of endogenous organic acids, in particular the positions of hydroxyl groups on the lactone ring of 4-butanolide, may be important in feeding modulation by conveying intrinsically reciprocal signals to neurons involved in feeding and satiety.

Animals↗

PubMed1988

Hypothalamic food intake regulating areas are involved in the homeostasis of blood glucose and plasma FFA levels.

The hypothalamus fulfills multiple functions, e.g., integration of food and water ingestion, various forms of social behavior and physiological neuroendocrine activities. Hypothalamic areas, particularly the ventromedial, lateral and paraventricular areas (VMH, LHA and PVN respectively), that contribute to the regulation of food intake are also involved in the regulation of blood glucose and plasma free fatty acid (FFA) levels. This regulation is controlled both directly via neural pathways and indirectly by hormones, e.g., insulin, glucagon, norepinephrine (NE) and epinephrine (E). A description is presented of the intrahypothalamic connections and the pathways between the hypothalamus and the motor areas of both the sympathetic system in the spinal cord (the intermediolateral column IML) and the parasympathetic system in the brainstem (the dorsal motornucleus of the vagus and the nucleus ambiguus). Noradrenergic stimulation of the LHA, VMH and PVN can alter blood glucose, plasma FFA and insulin levels independently of each other, e.g., noradrenergic stimulation of the VMH leads to an increase of insulin, glucose and FFA. Exercise induced increases of glucose are suppressed by alpha-adrenergic blockade of the LHA, VMH and PVN. Alpha-adrenergic blockade of the VMH during exercise causes an exaggerated increase of plasma FFA whereas alpha-blockade of both the LHA and PVN does not change the normal exercise induced increase of plasma FFA. The apparent contradiction that both adrenergic stimulation and adrenergic blockade of the VMH result in an increase in FFA may be explained by assuming postsynaptic alpha- and beta-adrenergic receptors in the VMH controlling glucose and FFA release respectively and FFA release and presynaptic inhibitory alpha-adrenergic receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1988

Penetration of peripheral glucose and insulin into cerebrospinal fluid in rats.

In this study the penetration of plasma insulin and glucose into the cerebrospinal fluid (CSF) was investigated. Rats were implanted with cannulas in the cisterna magna and into the left and right jugular veins. Freely moving rats were intravenously infused during 4 h with either glucose solution (10 mg/min) or saline. Before, during, and after the infusions, simultaneous blood and CSF samples were taken. Infusion of glucose led to an immediate rise of both plasma glucose and insulin. Although CSF glucose followed plasma glucose within 10 min, CSF insulin was unchanged until 40 min. After termination of the glucose infusion, levels of all substances returned to base line within 10 min. Twenty-four-hour food deprivation resulted in a significant decrease of plasma glucose, plasma insulin, CSF glucose, and CSF insulin. At the onset of eating after deprivation, an increase of plasma glucose and insulin occurred within 10 min, whereas CSF glucose was delayed between 10 and 40 min, after which ad libitum values were attained or surpassed. CSF insulin always remained below ad libitum levels. It is concluded that 1) glucose and insulin penetrate into the CSF and 2) CSF insulin and glucose can fulfill a putative feedback in homeostatic control of food intake and body weight.

Animals↗

PubMed1988

Central and peripheral adrenoceptors affect glucose, free fatty acids, and insulin in exercising rats.

The effects of intravenously and intrahypothalamically administered alpha- and beta-adrenoceptor antagonists on exercise-induced alterations in blood glucose, plasma free fatty acids (FFA), and insulin were investigated in rats. Exercise consisted of strenuous swimming against a counter current for 15 min. Before, during, and after swimming, blood samples were withdrawn through a permanent heart catheter. Intravenous administration of the alpha-blocker phentolamine led to a reduction in glucose and a substantial increase in insulin levels. Infusion of phentolamine through permanent bilateral cannulas into either the ventromedial or lateral area of the hypothalamus (VMH and LHA, respectively) completely prevented the increase in glucose while the decline in insulin was unaffected. Infusion of phentolamine into the VMH caused much higher plasma FFA levels than in controls. The beta-blocker timolol given intravenously caused a delayed increase in glucose and prevented the increase in FFA. Infusion of timolol into either VMH or LHA caused a delay in the increase in both glucose and FFA. The results suggest that 1) both peripheral and hypothalamic adrenoceptors are involved in energy metabolism during exercise and 2) FFA, glucose, and insulin concentrations in blood are independently regulated by VMH and LHA.

Animals↗

PubMed1988

[Hormonal modifications induced by food intake contribute to the regulation of the body weight and to metabolic variations].

In the rat the energy content of the body is subject to homeostatic control. The level of energy content depends on internal and external conditions. In the adult individual food intake is matched exactly to energy expenditure. Food intake leads to profound alterations in several hormonal plasma levels affecting metabolism e.g. insulin, glucagon and catecholamines. These hormones play an important feedback role in the storage and depletion of reserve tissues such as liver and fat cells. In this paper it is discussed that messages reporting energy content of the body may influence feeding motivation and that the CNS and especially the hypothalamus plays a directing role in this respect. Among these motivation setting messages the pancreatic hormones insulin and glucagon may be prominent factors in respectively long- and short-term regulation of food intake.

Adipose Tissue↗

PubMed1987

Daily variation of food-induced changes in blood glucose and insulin in the rat and the control by the suprachiasmatic nucleus and the vagus nerve.

Rats were provided with permanent cardiac catheters allowing free movement and blood sampling without anaesthesia. During food intake the increments of plasma insulin and blood glucose were smaller and more slowly increasing in the light phase than during the dark phase. After vagal blockade the increase in both blood glucose and plasma insulin was reduced. Since this effect was more prominent in the dark phase it suggests that during this phase vagal activity may stimulate an increase in glucose inflow into the blood by activating transport and digestion of food. Electrolytic lesions of the nucleus suprachiasmaticus caused disappearance of the circadian variation of insulin and glucose responses. In this situation in both phases rapid increments of insulin and glucose occurred similar to the controls during the dark phase. It is suggested that the nucleus suprachiasmaticus directly or indirectly controls vagal activity, which determines via its influence on the gastrointestinal tract the circadian variation in blood glucose and plasma insulin responses after food intake.

Animals↗