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J H Strubbe

Publications and source records attributed to J H Strubbe.

At least 37 records · Page 2Linked to original sources
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

Patterns of body temperature during feeding in rats under varying ambient temperatures.

Relationships between feeding and body temperature of rats were investigated at three ambient temperatures during the whole light/dark cycle. Basal liver temperature was negatively correlated with ambient temperature. Only at 29 degrees C liver temperature indicated activation of autonomic and locomotory thermoregulatory responses due to heat stress. At 21 degrees C, liver temperature was always higher than skin temperature. Both showed a clear circadian rhythm with higher values during the dark phase. Meal-associated temperature patterns were superimposed on this circadian rhythm. Liver and skin temperatures showed a preprandial and prandial rise. Liver temperature reached an almost similar peak value just above 39 degrees C at the end of a meal, irrespective of meal size and ambient temperatures of 13 degrees C and 21 degrees C. Liver temperature reached this peak about 2 min earlier and dropped sooner than skin temperature. These results indicate a threshold liver temperature at which feeding activity stops. The present study suggests that temperatures do not exceed this value by adaptive autonomic thermoregulatory responses shifting heat flow from core to skin and by stopping all locomotory activities including feeding, thereby avoiding deterioration of vital organs and physiological processes due to hyperthermia.

Animals↗
PubMed1992

Immunocytochemical localization of muscarinic acetylcholine receptors in the rat endocrine pancreas.

Immunocytochemical application of the antimuscarinic acetylcholine receptor antibody M35 to pancreas tissue revealed the target areas for the parasympathetic nervous system. Immunoreactivity in the endocrine pancreas was much higher than that in the exocrine part. Moreover, the endocrine cells at the periphery of the islets of Langerhans displayed the highest level of immunoreactivity. Based on these findings in the mantle of the islets, two types of islets have been distinguished: type-I islets with intensely stained mantle cells, and type-II islets with a much lower concentration of these cells. On average, type-I islets were larger (244.8 microns +/- 6.1 SEM) than type-II islets (121.5 microns +/- 3.8 SEM). M35-immunoreactivity was present on the majority of D cells, which were characterized by their immunoreactivity to somatostatin [of 446 D cells 356 (79.8%) were M35-immunopositive]. However, only a small proportion of the intensely stained mantle cells belonged to the D cell population. Therefore, it is concluded that the majority of the intensely stained mantle cells represent glucagon-secreting A and/or pancreatic polypeptide-secreting F cells. The intensity of M35-immunoreactivity at the periphery and central core of the islets paralleled the density of cholinergic innervation, suggesting a positive correlation between the intensity of cholinergic transmission and the number of muscarinic acetylcholine receptors at the target structures. The present study further revealed some striking parallels for the muscarinic acetylcholine receptor characteristics between the (endocrine) pancreas and the central nervous system.

Animals↗
PubMed1992

Insulin secretion by rat islet isografts of a defined endocrine volume after transplantation to three different sites.

We have analysed the graft function of rat islet isografts of identical and well-defined endocrine volumes after transplantation to three different sites (kidney, liver and spleen). Graft endocrine mass was determined by measuring the total islet volume prior to transplantation and was chosen to be similar to the endocrine volume in the normal adult rat pancreas. Graft function was tested in unanaesthetized, unstressed rats by the responses to glucose infusion and to a meal. All transplanted animals returned to normoglycaemia within one week after transplantation. At one month, basal glucose and insulin levels were similar to controls in rats with grafts to the spleen, but higher in rats with grafts to the kidney or liver. Irrespective of the transplantation site, recipients had higher glucose and lower insulin levels than controls in response to glucose infusion, but in response to a meal these differences from normal were less obvious. Finally, recipients showed both an acute insulin response to glucose infusion as well as a pre-absorptive insulin release after food ingestion, irrespective of the transplantation site. Our findings indicate that the insulin response to glucose infusion and to a meal is quantitatively reduced, but qualitatively intact after transplantation to the kidney, liver or spleen.

Animals↗
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↗
PubMed1992

Parasympathetic involvement in rapid meal-associated conditioned insulin secretion in the rat.

Blood glucose and plasma insulin concentrations were measured in blood sampled via a cardiac catheter in freely moving rats. To obtain a rapid conditioned cephalic phase of insulin secretion, rats were habituated to one of two feeding schedules. Clock-activated opening of doors in front of the food hopper imposed a feeding schedule of either six meals per day or two meals per day. When the doors were opened in both conditions, insulin increased rapidly during the first minute of feeding in the middle of the light phase. However, when presented an empty food hopper immediately after door opening, only rats in the two meal per day condition showed raised insulin levels and not rats in the six meal per day condition. This response was abolished following pharmacological blockade of nicotinic receptors with hexamethonium and muscarinic receptors with atropine. The present study shows that rapid conditioned insulin secretion can be evoked within one minute by a meal-associated stimulus. These results further indicate that this conditioned insulin secretion is vagally mediated and that its occurrence is dependent on the nature of the feeding schedule.

Animals↗
PubMed1991

Glucose tolerance and plasma insulin response to intravenous glucose infusion and test meal in rats with microencapsulated islet allografts.

Albino Oxford rats made diabetic with 75 mg/kg streptozotocin were intraperitoneally transplanted with 2500-2900 alginate-polylysine microencapsulated Lewis islets (n = 9, total islet tissue volume 8.0-11.0 microliters), or a similar volume of non-encapsulated Lewis islets (n = 5). All rats with microencapsulated islets became normoglycaemic, and remained normoglycaemic for 5-16 weeks. In rats with non-encapsulated islet grafts, only a temporary decrease in blood glucose was observed, and all were again severely hyperglycaemic at 1 week after implantation. At 5-6 weeks after transplantation, glucose tolerance in rats with microencapsulated islets was tested by intravenous glucose infusion (10 mg/min over 20 min) and test meal administration (n = 4). During glucose infusion, maximum glucose levels were 13.0 +/- 0.4 mmol/l in rats with microcapsules and 8.9 +/- 0.4 mmol/l in healthy control rats (p less than 0.01). Concomitant maximum plasma insulin levels were 215 +/- 17 pmol/l in rats with microcapsules and 715 +/- 85 pmol/l in controls (p less than 0.001). After the test meal, maximum blood glucose was 10.6 +/- 0.9 mmol/l in rats with microcapsules and 6.2 +/- 0.1 mmol/l in controls (p less than 0.001), with concomitant maximum plasma insulin levels of 247 +/- 11 pmol/l and 586 +/- 59 pmol/l, respectively (p less than 0.001). In conclusion, although the glucose tolerance is impaired and plasma insulin responses to intravenous glucose-load and test-meal are reduced, the alginate-polylysine membrane does provide adequate immunoisolation for the prolongation of allograft survival, resulting in prolonged normoglycaemia in streptozotocin diabetic rats.

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

Reduced preabsorptive insulin response in aged rats: differential effects of amphetamine and arginine-vasopressin.

The experiments presented here have been designed to investigated whether the age-related attenuation of the vagal reactivity to emotional stressors and its modulation by amphetamine (Amph) or arginine-vasopressin (AVP) can be generalized for other physiological response patterns. We therefore studied the vagal control of the endocrine pancreas during food intake. Young (3 months old) and aged (27 months old) male Wistar rats were provided with permanent cardiac catheters allowing free movement and repeated, stress-free blood sampling. The vagally mediated preabsorptive insulin response (PIR) in relation to food intake as seen in young rats was reduced in aged ones. Blood glucose increments were the same at both ages. Administration of Amph (0.5 mg/kg; s.c.) 30 min before, or AVP (10 micrograms/kg; s.c.) 60 min before presentation of a test meal led to an elevation of the magnitude of insulin secretion in young rats but reduced the response in aged rats. Moreover, the PIR was not reinstated in aged rats. Blood glucose increments were not influenced by the treatments. The results are interpreted in terms of age-related general reduction of parasympathetic reactivity. The differential effect of amphetamine and AVP treatment on the insulin response suggests that the central aminergic or peptidergic drive of vagal output to the endocrine pancreas is also age-related.

Aging↗
PubMed1991

The efficacy of intraperitoneal pancreatic islet isografts in the reversal of diabetes in rats.

The peritoneal cavity is of renewed interest for pancreatic islet transplantation, since it is the preferable site for transplantation of immunoisolated islets. In this study we investigated the minimum islet graft volume needed to restore normoglycemia after free intraperitoneal isogenic transplantation in streptozotocin diabetic rats. Furthermore, graft function was tested by measuring glucose and insulin response to an intravenous glucose load and spontaneously ingested carbohydrate-rich meal. Three graft volumes were used: 8.0-10.0 (group A); 4.0-5.0 (group B); and 2.0-2.3 microliters (group C); 1 microliter contained about 300 islets. All 10 rats in group A and 7 out of 9 rats in group B became normoglycemic for at least 6 months posttransplant, with blood glucose levels not significantly different from normal control animals. Only 3 out of 9 animals in group C became normoglycemic and never for longer than 3 months. The insulin responses to IVGTT in group A and group B were proportional to the grafted islet volume and always significantly lower than those of normal control rats. The insulin response to the test meal showed a similar tendency, which was found to be associated with the absence of preabsorptive insulin secretion. Maximum postprandial blood glucose levels in group A and group B were 0.8 and 1.5 mM higher than in normal control rats. We conclude that intraperitoneal transplantation of at least 4.0-5.0-microliters islet tissue is needed to reverse blood glucose in streptozotocin diabetic rats, and that glucose and insulin levels on IVGTT and test meal in rats with islet grafts of 8.0-10.0 microliters are not completely normalized. It is suggested that the impaired glucose tolerance is due to an insufficient beta-cell mass and a lack of parasympathetic innervation of the transplanted islet tissue.

Animals↗
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

The central amygdala is involved in the conditioned but not in the meal-induced cephalic insulin response in the rat.

The central nucleus of the amygdala (CEA) is considered to be involved in the regulation of autonomic correlates of fear. Its involvement in the control of autonomic functions other than elicited by fear has received little attention. The effects of a bilateral electrolytical lesion of the CEA on feeding related insulin responses have been analyzed in male Wistar rats. The cephalic phase of the insulin response is a vagally mediated elevation of plasma insulin concentration during the first minute after meal onset, before any increase in plasma glucose can be noticed. This response can also be entrained to environmental stimuli. The insulin response elicited under these conditions is due to conditioning. CEA lesioning abolished the conditioned insulin response but not the early insulin elevation during the presentation of food. The CEA lesion failed to affect plasma glucose levels in both the meal-induced and conditioned test situations. To our knowledge this is the first study that shows that the CEA is also involved in the organization of conditioned metabolic endocrine responses.

Amygdala↗
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

Behavioral and cardiac responses to a sudden change in environmental stimuli: effect of forced shift in food intake.

In order to test the possibility of a change in stress susceptibility induced by a forced change in activity rhythm, during control weeks food availability was restricted to the dark period only (fa-D) and to the light period only during the test week (fa-L). Stress susceptibility was measured on the basis of the decrease in heart rate (bradycardia) and an increase in freezing behavior in response to a sudden reduction in background noise. A significant increase in bradycardia both in magnitude and duration was observed during fa-L conditions as compared to the control fa-D condition. Also the duration of freezing behavior was increased during the fa-L condition. These results support the hypothesis that forced changes in circadian activities affect stress susceptibility. The significance of this finding for the incidence of stress pathologies is discussed.

Activity Cycles↗
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↗