Insulin Levels In Rats Research Articles

Indications of pre- and post-synaptic 5-HT 1A receptor interactions in feeding behavior and neuroendocrine regulation

This bipartite study uses behavioral and biochemical means to explore the involvement of both pre- and post-synaptic 5-HT 1A receptors in the control of food intake and neuroendocrine regulation. In the pharmacological study, the administration of the 5-HT 1A receptor agonist 8-hydroxy-2-(di- n-propylamino) tetralin (8-OH-DPAT; 60 μg/kg b.wt., i.p.) to rats caused a significant increase in 2 h intake of a high carbohydrate (CARB)/sugar diet ( P < 0.05) during the relatively inactive feeding period of the late light cycle. No significant change was detected in the intake of Purina laboratory chow at 2 h, or of the intake of either diet at 4 h and 24 h after 8-OH-DPAT administration. Injection of 8-OH-DPAT induced a drop in insulin levels in rats maintained on high CARB/sugar diets only (−90%; P<0.05). It also caused an increase in circulating glucose levels in both high CARB/sugar (240%; P<0.01) and chow fed (123%; P<0.05) rats; it did so more intensely in high CARB/sugar-fed rats. In the biochemical study, radioligand binding techniques were used to assess 5-HT 1A receptor density in the hypothalamus, as well as the relationship between 5-HT 1A receptors and circulating levels of insulin and glucose. Chronic and acute administration (25 mg/kg b.wt./5 injections, and 50 mg/kg b.wt., respectively, i.p.) of the potent hypoglyce mic agent tolbutamide (TOL) caused a significant increase in 5-HT 1A receptor density (+243% and +132.6%, respectively; P<0.05) in the medial hypothalamus but not in the lateral hypothalamus, as compared to vehicle-treated rats. Chronic glucose replacement therapy showed a trend towards reversing the depressed circulating glucose levels as well as the medial hypothalamic 5-HT 1A receptor density to control levels. These studies indicate that the pre-synaptic mechanism of 8-OH-DPAT-induced hyperphagia may require specific circulating levels of insulin and glucose, which are regulated via post-synaptic 5-HT 1A receptors.

Effects of Exercise and Diet on Weight Gain During Nicotine Cessation in Rats1

The present experiment examined the effects of exercise and the prevention of access to sweet food on nicotine cessation‐induced changes in body weight, body fat, and plasma insulin levels in rats. As in previous studies, nicotine administration reduced body weight gain and sweet food consumption, and nicotine cessation increased body weight gain and sweet food consumption. Exercise (swimming) reduced nicotine cessation‐induced increases in weight gain and body fat, and reduced plasma insulin levels. Preventing access to sweet food also reduces plasma insulin levels and body fat, but did not reduce weight gain. Insulin sensitivity is discussed as a possible mechanism for changes in body weight resulting from nicotine administration and cessation. In addition, the possible implications of these findings for behavioral and pharmacological interventions to prevent weight gain induced by smoking cessation are presented.

Comparison of the effects of efaroxan and glibenclamide on plasma glucose and insulin levels in rats

The effect of efaroxan (1 and 5 mg/kg p.o.; a selective α 2-adrenoceptor antagonist) was compared to glibenclamide (1 and 5 mg/kg p.o.; a standard sulphonylurea) on basal plasma glucose levels of fed and fasted rats. In addition, the effect of efaroxan (5 mg/kg p.o.) and glibenclamide (2 or 5 mg/kg p.o.), alone and in combination, on the hyperglycaemia and hyperinsulinaemia induced by glucose challenges, were investigated. An intra-arterial (250 mg/kg i.a.) and a subcutaneous (1 g/kg s.c.) glucose challenge were used to stimulate the fast and slow release phases of insulin secretion. Efaroxan increased plasma insulin levels in both conscious fed and fasted rats without greatly affecting plasma glucose levels. Glibenclamide also elevated insulin levels, but was associated with marked hypoglycaemia. Efaroxan and glibenclamide potentiated the slow and fast release of insulin secretion, but glibenclamide had a tendency to produce hypoglycaemia in these test situations, a property not shared by efaroxan. A combination of efaroxan and glibenclamide produced a greater elevation in the slow and fast insulin release phases than either compound alone, but did not enhance the hypoglycaemia seen with glibenclamide alone. These results provide further evidence that pancreatic α 2-adrenoceptors are involved in the regulation of insulin secretion.

Changes in copper and zinc ion concentrations and serum insulin level in rats affected by inbreeding and stress

SummaryThe effect of inbreeding level and sex on serum levels Cu, Zn and insulin in rats under stress was studied. F1‐hybrids of wild Norway rats (Rattus norvegicus Erxleben) and albino outbred rats (Ipf: RIZ), reached various inbreeding levels by full‐sub mating: control (0% inbred) and 50% and 91%. Each of the three groups consisted of 120 rats (60 males and 60 females). Half of each group (30 males and 30 females) was exposed only to ether anaesthesia (EA) to collect blood, the other half was exposed to severe physical stress (PS) — 3 d starvation and 3 h swimming, followed by ether anaesthesia. Using ATOM‐SPEC method, serum Cu, Zn ion concentrations were determined, whereas RIA was applied to determine serum insulin level.Significant linear decrease in mean values of serum Cu and Zn as well as insulin induced by increased inbreeding, especially under severe stress (PS) was noticed. Sex affected significantly mean values of serum insulin and Zn. Marked effects of inbreeding level and PS interaction on serum Cu and insulin was found as well.ZusammenfassungVeränderungen in den Ionkonzentrationen von Zink und Kupfer und Insulin‐Konzentration im Blutserum bei Ratten verschiedenen Inzuchtgrades und StressesBei Ratten unterschiedlichen Inzuchtgrades (0%, 50% und 91%) wurden nach physischem Stress (3 Tage Hungern und 3 h Schwimmen) die Konzentrationen von Zink und Kupfer Ionen und Insulin im Blutserum untersucht. Der Ausgangselternbestand (0% Inzucht) waren F1‐Kreuzungen von wilden Wanderratten (Rattus norvegicus Erxleben) mit weißen Ratten der nichtverwandten Linie Ipf: RIZ.Es wurde ein signifikanter Zusammenhang zwischen dem Inzuchtgrad und der Konzentration von Zink und Kupfer Ionen und Insulin im Blutserum festgestellt. Dieser Zusammenhang beruhte im wesentlichen (p ≤ 0,01) auf Rückgang der Konzentration beider Ionen (Zn+2 und Cu+2) und des Insulins mit zunehmendem Inzuchtgrad.Es wurde auch ein signifikanter Einfluß von Stress auf die Konzentration von Ionen (Zn+2 und Cu+2) und Insulin festgestellt. Ionen und Insulinniveau sank. Es wurde auch ein signifikanter Geschlechtseinfluß auf die Konzentration von Insulin und Zn+2 Ionen im Blutserum von Ratten festgestellt sowie eine Interaktion zwischen Stress und Inzuchtspiegel im Fall von Insulin und Cu+2 Ionen.RésuméLes changements de la concentration des ions de cuivre et de zinc et d'insuline chez les rats, sous l'influence de different taux d'inbreeding soumis a des stress de deux typesChez les rats de different degrés d'inbreeding: 0%, 50% et 91% stresses physiquement (72 heures a jeun et 3 heures de bain) on a analisé des changements de concentration des iones de cuivre et zinc et de taux d'insuline.Troupeau de début (0% d'inbreeding) c'est composé des metisses F1 entre le rat sauvage nomad (Rattus norveqicus Erxleben) et de rat albino non‐consanguin Ipf: RIZ.On a constaté que le taux d'inbreeding a influencé significativement sur la teneur des ions de cuivre et zinc et de la concentration d'insuline du serum. Les concentrations de ions Cu, Zn et d'insuline ont diminués considerablement (p ≤ 0,01) a la façon lineare avec l'augentation de coefficient d'inbreeding. Nous avons constaté I'influence de sexe sur le taux d'insuline et des ions. Le stress a provoqué augmentation significative de la concentration d'insulin et des ions de cuivre. Interaction significative entre stress et niveau d'inbreeding a été seulement pour l'insulne et de Cu+2.ResumenEl cambio en la concentracion de las ionas Cu y Zn y de la insulina de diferentas grades de la homozygotidad sumetidos a dos modelos e estrésEn las ratas con diferente grado de inbredacion: 0%, 50% y 91% y bajo un estrés fisico (3 dias de hambruna y 3 horas de natación), se han examinado los cambios en la concentratión de las ionas Cu y Zn y los grados de la insulina. La manada initial progenitores (0% de inbredacion) eran una mezcla F1 entre ratas errantes salvajes (Rattus norvegicus Erxleben) y ratas blances de una manada sin parentezco Ipf: RIZ.Se constató que el nivel del inbred influia realmente en la concentracion de las ionas Cu, Zn y los grados de la insulina. La concentración de la insulina y de las ionas Cu y Zn bajaba significativmente (p ≤ 0,01) con el aumento del coeficiente del inbred. Dentro de la influencias geneticas que determinan la concentración de la insulina y de la ionas Zn se encuentra el sexo del animal.Sin embargo, la influencia del estrés en la concentracion de las ionas Cu y Zn y de la insulina estaba significativa. También las interacciones entre las factores examinados (inbredación, estrés) tuberon una importante influencia en la concentración de las ionas Cu y de la insulina.

O-084 - Effects of selenium on the serum glucose and Insulin levels In diabetic rats

We investigated the effects of selenium (Se) on the serum glucose and insulin levels in rats with diabetes induced by streptozotocin (STZ, 75 mg/kg, i.p.) and pancreatectomized rats. Moreover, the direct action of Se on insulin release from the isolated pancreatic islets using a slight diabetic rat was studied. The following results were obtained: 1) Selenite at a dose of 173 micrograms/kg (78.9 micrograms/kg of Se base equivalent) drastically reduced the very high level of serum glucose in acute diabetic rats within 5 to 30 min after treatment. During this time period, the insulin level in the serum showed an increasing tendency. 2) The high serum glucose level in chronic diabetic rats returned to the original level with injection of selenite for 4 days, once a day. However, Se did not elicit a significant increase in serum insulin level. 3) Although there was a tendency for the serum glucose level to decrease when selenite was administered into pancreatectomized rats, no secretion of insulin into the serum was observed. 4) Insulin release from isolated pancreatic islets was dose-dependently accelerated by the addition of selenite. These data present the new finding that Se reduced the high level of serum glucose in diabetic rats.

Effects of selenium on the serum glucose and insulin levels in diabetic rats

We investigated the effects of selenium (Se) on the serum glucose and insulin levels in rats with diabetes induced by streptozotocin (STZ, 75 mg/kg, i.p.) and pancreatectomized rats. Moreover, the direct action of Se on insulin release from the isolated pancreatic islets using a slight diabetic rat was studied. The following results were obtained: 1) Selenite at a dose of 173 micrograms/kg (78.9 micrograms/kg of Se base equivalent) drastically reduced the very high level of serum glucose in acute diabetic rats within 5 to 30 min after treatment. During this time period, the insulin level in the serum showed an increasing tendency. 2) The high serum glucose level in chronic diabetic rats returned to the original level with injection of selenite for 4 days, once a day. However, Se did not elicit a significant increase in serum insulin level. 3) Although there was a tendency for the serum glucose level to decrease when selenite was administered into pancreatectomized rats, no secretion of insulin into the serum was observed. 4) Insulin release from isolated pancreatic islets was dose-dependently accelerated by the addition of selenite. These data present the new finding that Se reduced the high level of serum glucose in diabetic rats.

P-536 - The effects of selenium on the serum glucose and insulin Levels in rats.

P-536 - The effects of selenium on the serum glucose and insulin Levels in rats.

Promotion of nasal absorption of insulin by glycyrrhetinic acid derivatives. I.

Nasal absorption of insulin in rats was enhanced by addition of sodium glycyrrhetinate (GA Na), dipotassium glycyrrhizinate (GZ K2), and carbenoxolone (glycyrrhetinic acid hydrogen succinate) disodium salt (GAHS Na2). The latter agent was the most effective. On addition of 1% GAHS Na2, plasma immunoreactive insulin levels in rats showed a maximum level of 0.75 mU/ml at 15 min and plasma glucose levels were decreased to about 25 mg/dl after nasal administration of 10 U/kg insulin. In a comparison of the absorption rates of insulin by nasal and intravenous (i.v.) routes in rats, nasal absorptions of 10 U/kg insulin in the presence of 1% GAHS Na2, 0.5% GA Na and 1% GZ K2 were 26.5%, 13.2% and 14.5% of that in the case of a 5 U/kg i.v. dose, respectively. Hemolytic activies of GAHS Na2, GA Na and GZ K2 were milder than those of Na caprate and Na laurate, and nasal leucine aminopeptidase activity was more strongly inhibited by GAHS Na2 than by medium chain fatty acid salts, sodium glycocholate, GA Na or GZ K2. Therefore, it is suggested that GAHS Na2 is a very useful promoter which dose not irritate the nasal mucosal membrane or degrade insulin.

Effects of guar and carob gums on glucose, insulin and cholesterol plasma levels in the rat

AbstractGuar gum, obtained from the seeds of Cyamopsis tetragonolobus (L.) Taub. (Leguminosae), and carob gum, obtained from the seeds of Ceratonia siliqua L. (Leguminosae), were investigated for their effect on body weight, blood glucose and insulin levels in rats fed on a diet containing 15% of guar or carob gums for 2 to 6 consecutive weeks. At the same time, cholesterol plasma levels were assayed. A decrease in both plasma glucose and IRI levels together with a decreased haematic cholesterol level were observed.

P-6-14 Alteration of fructose-2,6-bisphosphate metabolism related to changes in serum insulin level in rats

P-6-14 Alteration of fructose-2,6-bisphosphate metabolism related to changes in serum insulin level in rats

Effect of vagotomy on serum insulin in rats with paraventricular or ventromedial hypothalamic lesions.

The effects of vagotomy on plasma glucose and insulin levels in rats with paraventricular nuclear (PVN) or ventromedial hypothalamic (VMH) lesions were measured during a constant glucose infusion. In one experiment, vagotomy was performed 50 min after the lesions, and in a second experiment, it was performed at the same time as the lesions. After the introduction of lesions in the PVN, there was a significantly greater rise in plasma glucose than in animals with either large or small VMH lesions, both of which had plasma glucose values similar to those in the sham-lesioned animals. The rise in insulin was greater in all three lesion groups than in the sham-operated animals. Although both plasma glucose and insulin had begun to decline before the vagotomy performed 50 min after lesioning, there was a further subsequent fall after vagotomy which was greater in the VMH-lesioned animals with large lesions than in rats with PVN lesions or small VMH lesions. In the sham-lesioned rats, there was no significant change in insulin or glucose after vagotomy. When the vagotomy and hypothalamic lesions were performed simultaneously, the glucose and insulin values in all groups were the same. The present experiments suggest that VMH and PVN exert different controls over pancreatic hormone secretion. The VMH lesions appear to remove an inhibitory effect on the vagus, with resultant hyperinsulinemia in the absence of hyperglycemia. The PVN-lesioned animals show a hyperglycemia which is abolished by vagotomy, suggesting that the PVN connects to vagal fibers which activate the glucagon secretory system in the alpha-cell of the pancreas.

Effect of GIP on insulin release to intravenous glucose infusion in hyperthyroid rats.

Triiodothyronine induced hyperthyroidism caused significantly elevated basal and stimulated glucose and insulin levels in rats. The release of Gastric Inhibitory Polypeptide (GIP) following an oral glucose load was not significantly different between euthyroid and hyperthyroid rats. The insulin response, however, was significantly higher in hyperthyroid rats. Following intravenous glucose hyperthyroid rats showed a diminished insulin response when compared with euthyroid rats but intravenous infusion of glucose together with GIP caused a significantly higher insulin response in hyperthyroid rats. It is hypothesized that in hyperthyroidism there is an increased sensitivity to the insulinotropic action of GIP and that this mechanism could emphasize the importance of the enteroinsular axis in pathophysiological states.

Starch availability in vitro and in vivo after flaking, steam-cooking and popping of wheat

The availability for digestion of starch in vitro after flaking, steam cooking and popping of whole grain wheat was studied and compared with that of raw and boiled wheat. Some physical and morphological characteristics were also investigated and correlated with starch availability for amylolysis. In an in vitro assay using hog pancreatic α-amylase after preincubation with pepsin, starch in flaked wheat was less available than that in boiled, popped and steam-cooked wheat. The starch in raw wheat was digested only slightly. When pepsin was omitted, the availability to α-amylase of starch in raw and boiled wheat decreased substantially, indicating that a large fraction of the starch was encapsulated in a protein matrix. The starch in flaked wheat elicited lower plasma glucose and plasma insulin levels in rats in vivo than that in boiled wheat after a gastric load. With raw wheat, the plasma glucose peak was much delayed and of lower magnitude compared with that with the heat-treated samples. In order to obtain good agreement with the in vivo results, a pepsin step had to be included in the in vitro assay using α-amylase. Differential scanning calorimetry measurements indicated that starch in flaked wheat was not gelatinised completely and this fact probably accounted for the lower availability in flaked wheat compared with boiled, popped or steam-cooked wheat.

Relationship between plasma corticosterone and insulin levels in rats with ventromedial hypothalamic lesions

The effects of ventromedial hypothalamic (VMH) lesions on plasma corticosterone, insulin, and glucose levels were studied in food-restricted and ad lib fed female rats. VMH lesions resulted in significant elevations of corticosterone and insulin levels compared to control values during the first 25 days after surgery. However, unlike insulin values which were generally greater in VMH rats fed ad lib than in food-restricted animals, plasma corticosterone levels were unaffected by level of food intake. Corticosterone and insulin levels were unrelated preoperatively and in sham-operated animals, but were positively correlated (r=.82) by Day 25 in ad lib fed VMH rats. It is concluded that the elevation in plasma glucocorticoids observed in VMH rats is a primary effect of the lesion that is independent of food intake or initial weight gain.

Effects of adrenal demedullation combined with chemical sympathectomy on cold-induced responses of endocrine pancreas in rats.

Adrenal demedullation combined with chemical sympathectomy with 6-hydroxydopamine (ACS) lowered plasma glucagon and insulin levels in rats. Acute cold exposure increased plasma glucagon in both ACS and control rats, while it increased plasma insulin only in ACS rats. ACS rats responded to cold with a smaller increase in plasma glycerol and a more pronounced elevation of plasma free fatty acids.

Route of administration as a factor in the selectivity of hormone suppression of a somatostatin analog in rats.

The method of administration of [D-Ala5,D-Trp8] somatostatin is of central importance in determining the degree and duration of suppression of insulin and glucagon release. The analog decreased insulin levels in rats when injected by s.c. or i.v. routes, with a nadir 15 minutes following injection. After i.v. injection, insulin levels rapidly returned to basal values while s.c. injection produced significant suppression for 60 minutes. Neither type of injection altered glucagon levels. Intravenous infusion resulted in inhibition of both insulin and glucagon release, with rebound hyperglucagonemia, but not hyperinsulinemia in the post-infusion period. Plasma glucose levels reflected these hormonal changes. Thus, dramatic alterations in the specificity of this somatostatin analog may be achieved by employing different methods of administration.

Serum Insulin Concentration, Insulin Release and Degradation, Glucose Tolerance and in Vivo Insulin Sensitivity in Cholesterol-Fed Rats

A series of experiments was conducted to elucidate the mechanism by which cholesterol feeding decreases serum insulin levels in rats and to determine the effect of this reduced insulin level on glucose metabolism. Rats were fed a casein-sucrose-soybean oil basal diet or this basal diet supplemented with 1% cholesterol (dissolved in hot oil) for periods longer than 30 days. Cholesterol feeding resulted in a decrease in serum insulin concentrations, although the decrease was not always significant. Cholesterol feeding did not affect fasting blood glucose levels, glucose tolerance, glucose-induced insulin release, pancreatic insulin content, in vivo insulin sensitivity, or in vitro glucose utilization in diaphragm and adipose tissue, but it significantly elevated the activity of liver glutathione-insulin transhydrogenase. On a per liver basis, the activity of this enzyme was approximately doubled. Results of this study suggest that cholesterol feeding has no significant effect on glucose utilization, but it can lead to a decrease in serum insulin concentration, probably by increasing the rate of insulin degradation in the liver.

Effects of thyroidectomy and thyroxine on plasma growth hormone and insulin levels in rats.

Plasma growth hormone and insulin levels were measured in normal, thyroidectomized (TX), and TX rats treated with 1-thyroxine (1-T4) or rat-growth hormone (r-GH). Although normal growth was observed 5 days after surgery, a decrease of circulating levels of GH was evidenced as early as 5 days after the operation. However, the plasma insulin levels were not affected by the 5th, 10th and 15th day of thyroidectomy. With a more prolonged thyroid hormone deprivation, the plasma insulin levels of TX rats remained lower than those of age-paired controls. Treatment of hypothyroid rats with 0.05 micron 1-T4 for 10 days induced growth and an increase in circulating GH levels, but had no effect on the low levels of plasma insulin of TX rats. Treatment of TX animals with 0.10 or 0.20 micron 1-T4, or 100 micron r-GH during 10 days caused plasma insulin levels to shift toward the values of their weight-paired controls. However, treatment of hypophysectomized (HX) rats with 0.20 micron T4 during 8 days did not change the circulating levels of plasma insulin. It is suggested that thyroid hormone deprivation results in a decrease of circulating levels of insulin secondary to a deficiency in growth hormone secretion. In addition, normal GH secretion appears to be required for normal pancreatic insulin secretion to occur.

Neurotensin and substance-P: Effects on plasma insulin and glucagon levels

N 'EUROTENSIN AND SUBSTANCE-P, a tridecapeptide and undecapeptide respectively, isolated from bovine hypothalamus by Leeman and co-workers? 2 are distributed throughout the brain and gastrointestinal tract as determined by specific radioimmunoassays. 3-6 Both peptides induce gut contraction in vitro and hypotension in vivo. 7,8 Recently neurotensin and substance-P have been reported to inhibit insulin secretion induced by glucose and arginine and to produce an elevation of plasma levels of glucose and glucagon and a decrease of plasma levels of insulin in rats. 9 This paper describes studies concerning the effects of these peptides on plasma levels of insulin and glucagon in the rat and the possible role of histamine in mediating their actions. Rats were housed and cared for as previously described, t~ Peptides were given via the jugular vein and blood samples obtained by decapitation (systemic blood) or by portal venipuncture in lightly ether-anesthetized animals. Insulin and glucagon determinations were performed as previously described. 1~ Neurotensin and substance-P were synthesized by Dr. Jean Rivier. All experiments were carried out in a randomized block design. Following analysis of variance, differences between treatments were determined by multiple range tests of Dunnett and Duncan. Table 1 shows the temporal effects of saline, neurotensin, and substance-P on portal vein and systemic plasma insulin and glucagon levels. Over this time course neurotensin and substance-P significantly reduces systemic plasma levels of insulin and elevated both portal vein and systemic plasma glucagon levels. Neither peptide significantly reduced portal vein levels of plasma insulin. In a recent publication concerning systemic plasma hormone measurements we suggested that neurotensin and substance-P might exert their glucose elevating effects via inhibition of pancreatic secretion of insulin and elevation of plasma glucagon. 9 Recent studies suggest that neurotensin and substance-P elevate levels of glucagon and either inhibit or stimulate insulin secretion, depending on the dose of peptide, in the effluent from the perfused dog pancreas in vitro, n Our current data comparing the effects of neurotensin and substance-P on portal vein and systemic plasma levels of insulin and glucagon suggest the development of an acute gradient of insulin concentration across the liver. Enhanced hepatic or systemic plasma binding, distribution or disposal of insulin could explain such results. The vasoactive properties of these peptides or their possible effects on mast cell histamine release may produce these effects. 7'8'~2

Somatomedin production in the neonatal rat.

The hormonal stimulus to rat fetal and neonatal somatic and skeletal growth has been investigated by a study of ciruclating somatomedin (SM), growth hormone (GH) and insulin levels in rats from 21 days in utero to 40 days of post natal life. Somatomedin activity could not be detected in the serum of fetal rats in which circulating GH and insulin levels were high. In early post natal life GH and insulin levels remained high but gradually declined reaching normal adult levels at 19 days and 40 days respectively. Somatomedin activity was measurable only at low levels until 11 days after birth and thereafter remained steady throughout the time period studied. These studies suggest that somatomedin alone is not responsible for the rapid growth of the rat in early neonatal life and it is suggested that insulin may also be active as a growth factor in this period.