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Biomedical subjects

B Balkan

Publications and source records attributed to B Balkan.

32 records · Page 2Linked to original sources
PubMed1994

Contribution of liver nerves, glucagon, and adrenaline to the glycaemic response to exercise in rats.

The contribution of hepatic sympathetic innervation, glucagon and adrenaline to the glycaemic response to exercise was investigated in rats. Hepatically denervated (LDX) or sham operated (SHAM) rats with permanent catheters were therefore submitted to swimming with or without infusion of somatostatin in combination with adrenodemedullation. Blood samples were taken for measurements of blood glucose, plasma free fatty acids (FFA), adrenaline (A), noradrenaline (NA), insulin and glucagon. Liver denervation by itself did not influence glucose levels during exercise. Infusion of somatostatin in SHAM animals, which inhibited the exercise-induced glucagon response, led to enhanced sympathoadrenal outflow (measured as plasma A and NA) and a reduced blood glucose during exercise, suggesting that glucagon serves as a powerful mediator of the glycaemic response during swimming. Infusion of somatostatin in LDX animals failed to enhance plasma NA levels and led to a more pronounced reduction in blood glucose levels. This indicates that liver nerves do contribute to the glycaemic response to exercise when glucagon secretion is suppressed. Reduced blood glucose levels after adrenodemedullation revealed that adrenal A is another important mediator of the glucose response to exercise. Infusion of somatostatin in adrenodemedullated SHAM or LDX animals was not accompanied with increased NA outflow, suggesting that adrenal A is necessary to allow the compensatory increased outflow of NA from sympathetic nerves. In conclusion, the study shows that pancreatic glucagon and adrenal A are the predominant factors influencing the glycaemic response to exercise, whereas a role of the sympathetic liver nerves becomes evident when glucagon secretion is suppressed.

Adrenal Medulla↗
PubMed1994

Glucosamine inhibits glucokinase in vitro and produces a glucose-specific impairment of in vivo insulin secretion in rats.

A characteristic feature of non-insulin-dependent diabetes mellitus (NIDDM) is the lack of an acute insulin response to intravenous glucose with maintenance of the response to other secretagogues. It has been hypothesized that impaired glucose sensing stems from defective beta-cell glucokinase. It remains unclear whether decreased pancreatic glucokinase activity will produce defects of insulin secretion similar to those observed in NIDDM. In this study, the effects of glucosamine on glucokinase activity and on islet function were assessed in vitro and in vivo. Glucosamine (5 mmol/l) reduced glucokinase activity in islet homogenate and diminished the insulin response to glucose (200 mg/dl) by isolated islets, whereas the response to arginine (20 mmol/l at 100 mg/dl glucose) was unaffected. In conscious normal rats, glucosamine lowered plasma insulin, followed by an increase in blood glucose. Administration of glucosamine 10 min before an infusion of glucose (10 mg.min-1. 15 min) reduced the insulin response. The primary effect was an attenuation of the first-phase insulin response relative to the decreased basal insulin levels. Arginine (10 mg.min-1.15 min) induced biphasic insulin release in both groups. Although glucosamine slightly reduced the absolute insulin response, it was normal relative to preinfusion levels. In all experiments, glucagon secretion was unaffected by glucosamine. The results indicate that glucosamine inhibits beta-cell glucokinase activity in vitro. In addition, glucosamine impairs glucose- but not arginine-induced insulin secretion. We conclude that glucosamine, probably via a reduction of glucokinase activity, impairs insulin secretion in a manner comparable to that seen in NIDDM.

Animals↗
PubMed1993

Overfeeding-induced obesity in rats: insulin sensitivity and autonomic regulation of metabolism.

The metabolic consequences of the development of obesity and the underlying mechanisms were investigated. For this purpose, male rats were overfed for 5 weeks through long-term gastric catheters. Permanent cardiac cannulas implanted before the overfeeding period allowed frequent blood sampling and infusions without disturbing the rats. Hyperalimented rats became grossly obese, displayed elevated basal plasma norepinephrine (NE) concentrations, and developed hyperinsulinemia and insulin insensitivity, but remained normoglycemic and preserved normal intravenous (IV) glucose tolerance. During physical exercise (ie, 15 minutes of swimming), obese rats displayed exaggerated increases in blood glucose concentrations, whereas plasma free fatty acid (FFA) responses were blunted. These alterations were probably due to decreased NE release by the sympathetic nervous system during exercise and to altered tissue responsivity to adrenergic stimulation. The latter was demonstrated by infusions of catecholamines in the resting state. Responses to mild stress were increased in obese animals, as indicated by increased responses of plasma epinephrine (E) and corticosterone during handling and first contact with water. The results of the present study indicate that overfeeding induces changes in the sympathetic control of metabolism and insulin secretion. Whereas elevated NE levels in the basal state probably reflect increased energy expenditure, the pattern of nutrient mobilization during exercise is directed toward sparing of fats.

Animals↗
PubMed1993

Influence of peri-arterial hepatic denervation on the glycemic response to exercise in rats.

Exercise is known to increase hepatic glucose production. Previous studies have suggested that the sympathetic nerves only marginally contribute to this process. This study examined whether increased catecholamine response or increased adrenoceptor sensitivity might have affected previous results showing no effect of hepatic denervation on the increased hepatic glucose production during exercise. Hepatic sympathetic denervated rats, sham-operated rats and control rats were forced to swim against a counter current for 15 minutes. Denervations and sham operations were performed 9 days prior to swimming. The results show that denervation did not affect the changes in levels of blood glucose, plasma FFA, and catecholamines before, during and after swimming. Furthermore, hepatic adrenoceptor sensitivity was not altered in denervated rats, since intravenous infusions of epinephrine (20 ng/min) and norepinephrine (50 ng/min) similarly changed blood glucose and plasma FFA levels in liver-denervated, sham-operated and control rats. Thus, the increase in blood glucose levels during intravenous infusion of epinephrine and norepinephrine in the respective groups was 1.2 +/- 0.3 and 1.0 +/- 0.3 mmol/l (liver-denervated rats), 1.6 +/- 0.4 and 0.7 +/- 0.3 mmol/l (sham-operated rats) and 1.3 +/- 0.3 and 0.8 +/- 0.3 mmol/l (control rats), respectively. After adrenodemedullation, however, the rise of glucose levels during swimming in liver-denervated and control rats was completely abolished. Thus, the glucose response to swimming with and without adrenodemullation was 0.1 +/- 0.4 and 1.7 +/- 0.4 mmol/l in liver-denervated rats (P < 0.01) and -0.2 +/- 0.4 and 2.2 +/- 0.2 mmol/l in control rats (P < 0.001), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenalectomy↗
PubMed1992

Sympathoadrenal function in genetically obese Zucker rats.

The effects of genetic obesity on the actions and alterations of the sympathetic nervous system were studied in 10-12-month-old obese (fa/fa) and lean (Fa/-) Zucker rats. Blood glucose, plasma insulin, epinephrine (E), norepinephrine (NE), and free fatty acids (FFA) concentrations were measured in blood samples taken through a permanent heart catheter before, during, and after exercise or intravenous infusion of E and NE. Baseline plasma FFA and insulin levels were markedly increased in the obese animals. Exercise, i.e., strenuous swimming against a counter current for 15 min, led to reduction of plasma insulin concentrations and an increase of all other blood components in lean Zucker rats. In obese animals, an exaggerated increase of blood glucose and a large suppression of plasma insulin occurred. Plasma FFA levels tended to decline during exercise. Plasma catecholamine patterns in the exercising fatty Zuckers were not different to those of the lean animals. Infusion of E caused an increase of blood glucose and a decrease of plasma insulin concentrations in both groups of animals. The increase in blood glucose in the obese animals was significantly larger compared to the changes in the lean animals. Infusion of NE significantly reduced plasma insulin concentration in obese but not in lean animals. The results revealed that activation of the sympathetic system, expressed as exercise-induced alterations in plasma E and NE levels, is normal in obese Zucker rats. However, postsynaptic receptor effects of catecholamines on glycogenolysis and lipolysis are different in obese and lean animals, which points to permanent changes in adrenoceptor mechanisms on adipocytes, hepatocytes, and muscle cells in obesity.

Adrenal Glands↗
PubMed1992

Exercise-induced sympathetic FFA mobilization in VMH-lesioned rats is normalized by fasting.

This study investigates whether reduced sympathetic responses during physical exercise in ventromedial hypothalamus (VMH)-lesioned obese rats are the direct result of damage to hypothalamic circuits or a secondary effect of the altered metabolism in obesity. Obese, VMH-lesioned rats and lean controls were deprived of food for 48 h and submitted to 15 min of swimming. Food-deprived lean and obese rats displayed increased free fatty acid mobilization and utilization, whereas blood glucose concentrations were decreased. Basal plasma insulin levels were reduced by fasting in both groups, when compared with the ad libitum situation, but remained higher in the obese animals. Fasting augmented the norepinephrine response of the obese rats, resulting in equal profiles in lean and obese animals. These results indicate that VMH-lesioned animals are able to increase the sympathetic activation of adipose tissue during exercise to overcome an energy deficiency. Therefore, the function of the VMH in the regulation of the sympathetic nervous system controlling metabolism can be taken over by redundant mechanisms. The reduced sympathetic activity in ad libitum fed VMH-lesioned animals is therefore likely to be the result of the altered metabolism.

Animals↗
PubMed1991

Hyperinsulinemia and glucose tolerance in obese rats with lesions of the ventromedial hypothalamus: dependence on food intake and route of administration.

This study was performed to investigate the consequences of developing obesity on glucose homeostasis in animals showing hyperphagia plus vagal hyperinsulinemia and rats that were normophagic and hyperinsulinemic. Male rats were lesioned in the ventromedial hypothalamus (VMH) and kept either under ad libitum or absolute (oral or intragastrical) pair-feeding conditions for 4 weeks. Hyperphagic rats, as well as normophagic VMH rats, became obese, but only ad lib-fed obese rats displayed glucose intolerance to intravenous (IV) glucose infusions. Orally pair-fed VMH rats also showed normal oral and intragastric glucose tolerance, but in intragastrically fed VMH animals and controls, oral and intragastric glucose tolerance was decreased. These results indicate that (1) obesity as a consequence of VMH lesions is not dependent on hyperphagia, confirming earlier reports, and also independent of the ingestion of bulk meals. (2) beta-cell release of insulin to IV glucose infusion is not sufficient when hyperphagia and vagally mediated hyperinsulinemia coincide, and is therefore dependent on several factors; and (3) oral glucose intolerance develops when preabsorptive reflexes are blunted, irrespective of whether the animals were hyperinsulinemic or not.

Administration, Oral↗
PubMed1991

Altered sympathetic control of nutrient mobilization during physical exercise after lesions in the VMH.

To study the impact of obesity on sympathetic nervous regulation of nutrient mobilization, obese rats and lean controls were subjected to physical exercise. Male Wistar rats, rendered obese by bilateral electrolytic lesions of the ventromedial hypothalamus (VMH) were subjected to 15 min swimming. Permanent cardiac catheters allowed frequent blood sampling. At rest, glucose, free fatty acids (FFA), and insulin concentrations were elevated in the obese animals, whereas catecholamine levels were similar in both groups. During exercise, glucose concentrations reached higher values in the lesioned rats, whereas these animals did not display the normal FFA increment. Plasma insulin concentrations were suppressed in both groups, and the rate of suppression was very similar when expressed as percentage change from resting levels. There was no difference in plasma epinephrine responses during swimming, but the increase in norepinephrine was diminished in the obese animals. The results suggest that obesity after VMH lesion leads to reduced stimulation of lipolysis by norepinephrine and a predominant mobilization of glucose during exercise, both favoring glucose utilization and the accumulation of fat.

Animals↗
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

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

Hepatic-portal and cardiac infusion of CCK-8 and glucagon induce different effects on feeding.

In order to compare effects of circulating CCK-8 and glucagon on food intake, rats were provided with a permanently implanted catheter in the right atrium. Another cannula was implanted into the hepatic-portal vein by a new technique. After a standard fasting period graded loads of CCK-8 and glucagon were infused via these catheters during refeeding. Intracardiac glucagon and CCK loads dose-dependently suppressed meal size. Intraportal infusion of glucagon caused similar suppression compared to intracardiac administration. This may indicate a minor role of the liver as a target for the suppression of feeding by glucagon. In contrast, intraportal infusion of CCK-8 did not reduce food intake. The results indicate that CCK-8 is removed or inactivated by the liver. It is suggested that CCK-8 acts locally on vagal nerve endings to exert its suppressive action on food intake.

Animals↗
PubMed1988

Changes in septo-hippocampal projections after lateral entorhinal or combined entorhinal-raphé lesions as studied by anterograde tracing methods.

Septal and entorhinal projections to the hippocampus show a considerable overlap in their target structures in the molecular layer of the dentate gyrus (DG) and stratum lacunosum-moleculare of the cornu ammonis (CA). Employing anterograde tracing methods, it was investigated in which way the morphological pattern of the septohippocampal projections were influenced by lateral entorhinal cortex (LEA) lesions. Anterograde filling of neurons from soma to axonal terminals with Phaseolus vulgaris leucoagglutinin (PHA-L) revealed lesion-induced changes in innervation patterns in the DG but not in CA fields. LEA lesions provoke an impressive shift of septo-dentate projections from a predominant middle molecular layer innervation to the outer molecular layer, whereas septal projections to the CA remain unchanged. Comparison with concurrent acetylcholinesterase (AChE) staining and immunocytochemical demonstration of choline acetyltransferase (ChAT) confirm the cholinergic nature of this plasticity response. This response was equally strong in unilateral or bilateral damage to the LEA and was neither enhanced nor inhibited by simultaneous injury to the median raphé nuclei.

Acetylcholinesterase↗
PubMedDate not supplied

Neuroendocrine factors regulating blood glucose, plasma FFA and insulin in the development of obesity.

A number of neurotransmitters and neuropeptides in the hypothalamus play a role in the control of food intake, metabolism, and body weight. Particularly, noradrenergic mechanisms in several areas of the hypothalamus are involved. Control of peripheral metabolism by the hypothalamus is achieved via autonomic modulation of the function of hepatocytes, adipocytes, and the endocrine cells in the islets of Langerhans. The autonomic control mechanisms ultimately lead to an appropriate shaping of blood glucose, plasma FFA, and insulin profiles to guarantee an adequate flow of nutrients under different physiological situations. Peripheral insulin and glucose can penetrate into the brain where they might affect the function of those brain structures involved in control of food intake, metabolism, and body weight.

Animals↗