Mechanisms by which endogenous glucocorticoid protects against indomethacin-induced gastric injury in rats

2002 ◽  
Vol 283 (5) ◽  
pp. G1082-G1089 ◽  
Author(s):  
Ludmila Filaretova ◽  
Akiko Tanaka ◽  
Tohru Miyazawa ◽  
Shinichi Kato ◽  
Koji Takeuchi
Keyword(s):  
Gastric Motility ◽  
Protective Action ◽  
Microvascular Permeability ◽  
Gastric Injury ◽  
Functional Disorders ◽  
Gastric Lesions ◽  
Inhibitory Effects ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Adrenalectomized Rats

We investigated the mechanisms underlying the protective action of glucocorticoids against indomethacin-induced gastric lesions. One-week adrenalectomized rats with or without corticosterone replacement (4 mg/kg sc) were administered indomethacin (25 mg/kg sc), and gastric secretion (acid, pepsin, and mucus), motility, microvascular permeability, and blood glucose levels were examined. Indomethacin caused gastric lesions in sham-operated rats, with an increase in gastric motility and microvascular permeability as well as a decrease in mucus secretion. Adrenalectomy significantly worsened the lesions and potentiated these functional disorders. Glucose levels were lowered by indomethacin in sham-operated rats, and this response was enhanced by adrenalectomy. The changes observed in adrenalectomized rats were prevented by supplementations of corticosterone at a dose mimicking the indomethacin-induced rise in corticosterone, whereas the protective effect of corticosterone was attenuated by RU-38486, a glucocorticoid receptor antagonist. We conclude that the gastroprotective action of endogenous glucocorticoids may be provided by their support of glucose homeostasis and inhibitory effects on enhanced gastric motility and microvascular permeability as well as maintaining the production of mucus.

THE EFFECT OF ADRENALECTOMY, DIHYDROERGOTAMINE, AND DIBENZYLINE ON THE SENSITIVITY OF RATS TO TOLBUTAMIDE

1963 ◽  
Vol 41 (10) ◽  
pp. 2189-2195 ◽  
Author(s):  
Rosemary D. Hawkins ◽  
R. E. Haist
Keyword(s):  
Blood Glucose ◽  
The Other ◽  
Compensatory Mechanisms ◽  
Blood Samples ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Significant Difference ◽  
Tail Blood ◽  
Adrenalectomized Rats ◽  
Intact Rats

In the rat, the magnitude of the hypoglycaemic response to a dose of tolbutamide (50 mg/kg per os) which does not depress blood glucose levels to the point where adrenal compensatory mechanisms are stimulated is unaffected by adrenalectomy. On the other hand, when a dose is given which induces a greater hypoglycaemia (100 mg/kg per os) a very significant difference between adrenalectomized and sham-operated animals is observed, the adrenalectomized rats displaying a far greater sensitivity to the hypoglycaemic action of this compound. In intact rats, the hypoglycaemia induced by tolbutamide (100 mg/kg per os) is lessened by pretreatment of the animals with Dibenzyline (4 mg/kg) but enhanced by the prior injection of dihydroergotamine (2 mg/kg). Larger doses of dihydroergotamine alone cause a reduction in glucose levels of tail blood which is greater than that found in carotid blood samples withdrawn at the same times.

Possible involvement of glucocorticoids in the reduction of serum insulin levels by interleukin-1 in the rat

1992 ◽  
Vol 132 (3) ◽  
pp. 419-423 ◽  
Author(s):  
H. Shimizu ◽  
Y. Uehara ◽  
Y. Tanaka ◽  
Y. Shimomura ◽  
I. Kobayashi
Keyword(s):  
Plasma Glucose ◽  
Serum Insulin ◽  
Protective Action ◽  
Interleukin 1 ◽  
Inflammatory Cells ◽  
Metabolic Effects ◽  
Immunoreactive Insulin ◽  
Glucose Levels ◽  
Adrenalectomized Rats ◽  
Intact Rats

ABSTRACT Evidence is accumulating that adrenal steroids may be involved in the metabolic effects of cytokines. We evaluated the possible involvement of glucocorticoids in the inhibition of pancreatic insulin secretion by interleukin-1β (IL-1β), one of the cytokines produced by inflammatory cells. In the first group of experiments, adrenalectomized rats showed a significant reduction in basal and glucose (0·5 g/kg, i.v.)-stimulated immunoreactive insulin (IRI) levels after injection of IL-1β (1·0 μg/kg), but intact rats did not. Pretreatment with IL-1β increased plasma glucose levels 2 and 15 min after an i.v. bolus of glucose in adrenalectomized rats. In the second group of experiments, dexamethasone supplement (0·1 mg/kg) given to adrenalectomized rats cancelled the reduction in plasma glucose levels by IL-1β, and rats treated with 1·0 mg dexamethasone/kg showed a significant increase in basal IRI levels and enhanced serum IRI levels after IL-1β injection. However, 1·0 mg deoxycorticosterone/kg given daily for 7 days failed to cancel the effect of IL-1β on the reduction of serum IRI levels, although it attenuated the weight loss after adrenalectomy. The data suggested that withdrawal of glucocorticoids after adrenalectomy potentiates the effect of IL-1β on the reduction of serum IRI levels. Glucocorticoids may have a protective action against the reduction of serum IRI levels by IL-1β. Journal of Endocrinology (1992) 132, 419–423

Central action of adrenomedullin to prevent ethanolinduced gastric injury through vagal pathways in rats

1998 ◽  
Vol 274 (6) ◽  
pp. R1783-R1788 ◽  
Author(s):  
Hiroshi Kaneko ◽  
Terunori Mitsuma ◽  
Hirofumi Nagai ◽  
Shozaburo Mori ◽  
Takashi Iyo ◽  
...  
Keyword(s):  
Wistar Rats ◽  
Protective Action ◽  
Gastric Injury ◽  
Central Action ◽  
Gastric Lesions ◽  
Protective Mechanisms ◽  
Calcitonin Gene ◽  
Intracisternal Injection ◽  
Specific Receptors ◽  
The Brain

Adrenomedullin (AM), belongs to the calcitonin gene-related peptide (CGRP) family and interacts with AM and CGRP1 receptors. Specific AM receptors and immunoreactivity are present in the rat brain. The effect of intracisternal injection of rat AM on ethanol-induced gastric lesions was studied in conscious Wistar rats. The peptide was injected intracisternally or intravenously under short anesthesia 20 min before intragastric injection of 70% ethanol. Corpus lesions were determined 1 h after ethanol. Intracisternal AM (75, 150, and 300 pmol) dose-dependently inhibited ethanol-induced gastric lesions by 40–72% and rat α-CGRP (150 pmol ic) by 76%. Intravenous AM (300 pmol) had no effect. The CGRP1 receptor antagonist CGRP-(8—37) (9.6–19.2 nmol ic) dose-dependently inhibited the protective effect of intracisternal α-CGRP but not that of AM. Subdiaphragmatic vagotomy and peripheral injection of atropine, indomethacin, or N G-nitro-l-arginine methyl ester (l-NAME) prevented AM protective action. l-Arginine but not d-arginine blockedl-NAME action. These data suggest that both AM and CGRP act in the brain to prevent ethanol-induced gastric lesions through interaction with their specific receptors. AM action may involve vagal cholinergic-dependent modulation of prostaglandins and nitric oxide protective mechanisms.

scholarly journals Blood-Glucose-Lowering Effect of Coptidis Rhizoma Extracts From Different Origins via Gut Microbiota Modulation in db/db Mice

2021 ◽  
Vol 12 ◽  
Author(s):  
Yuanfeng Lyu ◽  
Lin Lin ◽  
Yuning Xie ◽  
Dan Li ◽  
Min Xiao ◽  
...  
Keyword(s):  
Blood Glucose ◽  
Gut Microbiota ◽  
Model Assessment ◽  
Inhibitory Effects ◽  
Glucose Lowering ◽  
Atp Production ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Coptidis Rhizoma ◽  
Time Kill

Background:Coptidis rhizoma extracts (CREs) have been used widely for their anti-diabetic and anti-microbial activities, and berberine/jatrorrhizine/coptisine/palmatine are the primary bioactive components. Although guidelines have adopted content analyses of these components as a quality control method for CREs, it is difficult to differentiate the CREs from different sources using this method because of the lack of indications for their related pharmacological activities.Purpose: To explore the effect of CREs (CREA/CREB/CREC) with different compositions of major components on the gut microbiota and blood glucose levels in db/db mice.Methods: Degradation of berberine/jatrorrhizine/coptisine/palmatine from CREA/CREB/CREC in rat/mouse intestinal contents and their impact on nine common gastrointestinal bacteria were investigated. In addition, the effects of oral administration of CREA/CREB/CREC for 2 weeks on the gut microbiota and blood glucose levels in db/db mice were monitored via insulin/glucose tolerance test (ITT/GTT), insulin concentration, homeostatic model assessment of insulin resistance and fecal 16S rRNA sequencing.Results and Conclusion: The total amount of berberine/jatrorrhizine/coptisine/palmatine was highest in CREA. Clostridium perfringens was strongly inhibited by all three CREs, with CREA demonstrating the most significant inhibitory effects on minimum inhibitory concentration, time-kill kinetics, and ATP production. In db/db mice, CREA resulted in the most significant decrease in ITT/GTT and depicted different changes in the microbiota from CREB/CREC. Thus, CREs with different compositions of berberine/jatrorrhizine/coptisine/palmatine differed in terms of time-kill kinetics and ATP production assays on C. perfringens. CREA revealed the potent bacterial inhibitory effects and glucose-lowering activity.

AN EXTRA-ADRENAL DIABETOGENIC RESPONSE TO CORTICOTROPHIN IN THE RAT

1962 ◽  
Vol 41 (2) ◽  
pp. 227-233 ◽  
Author(s):  
Norman B. Marshall ◽  
F. Lee Richardson ◽  
Frank L. Engel
Keyword(s):  
Growth Hormone ◽  
Growth Hormone Treatment ◽  
Tube Feeding ◽  
Hormone Treatment ◽  
High Carbohydrate Diet ◽  
Carbohydrate Diet ◽  
Glucose Levels ◽  
High Carbohydrate ◽  
Blood Glucose Levels ◽  
Adrenalectomized Rats

ABSTRACT Sham-operated and adrenalectomized rats primed by tube-feeding a high carbohydrate diet and the daily administration of 5 mg of cortisone acetate were challenged at intervals with corticotrophin (ACTH) or growth hormone and suitable inert proteins as controls. Blood glucose levels, measured 1, 2, 3 and 4 hours after the ACTH, which was administered 3½ hours after the morning meal, showed a marked hyperglycaemic response in both intact and adrenalectomized rats tested up to the fifty-fifth day of forced-feeding and cortisone treatment. Oxidation of ACTH with H2O2 abolished the hyperglycaemic response, whereas reduction with cysteine restored activity. Growth hormone did not elicit hyperglycaemia in these experiments, in keeping with previous experience showing that several days of growth hormone treatment are required to elicit hyperglycaemia. Sham-operated and adrenalectomized rats receiving deoxycorticosterone responded to ACTH with hypoglycaemia, confirming earlier results. The conditions necessary to elicit the hyper- and hypoglycaemic extra-adrenal effects of ACTH are contrasted and discussed.

THE EFFECT OF ADRENALECTOMY, DIHYDROERGOTAMINE, AND DIBENZYLINE ON THE SENSITIVITY OF RATS TO TOLBUTAMIDE

1963 ◽  
Vol 41 (1) ◽  
pp. 2189-2195
Author(s):  
Rosemary D. Hawkins ◽  
R. E. Haist
Keyword(s):  
Blood Glucose ◽  
The Other ◽  
Compensatory Mechanisms ◽  
Blood Samples ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Significant Difference ◽  
Tail Blood ◽  
Adrenalectomized Rats ◽  
Intact Rats

In the rat, the magnitude of the hypoglycaemic response to a dose of tolbutamide (50 mg/kg per os) which does not depress blood glucose levels to the point where adrenal compensatory mechanisms are stimulated is unaffected by adrenalectomy. On the other hand, when a dose is given which induces a greater hypoglycaemia (100 mg/kg per os) a very significant difference between adrenalectomized and sham-operated animals is observed, the adrenalectomized rats displaying a far greater sensitivity to the hypoglycaemic action of this compound. In intact rats, the hypoglycaemia induced by tolbutamide (100 mg/kg per os) is lessened by pretreatment of the animals with Dibenzyline (4 mg/kg) but enhanced by the prior injection of dihydroergotamine (2 mg/kg). Larger doses of dihydroergotamine alone cause a reduction in glucose levels of tail blood which is greater than that found in carotid blood samples withdrawn at the same times.

scholarly journals Aspulvinones Suppress Postprandial Hyperglycemia as Potent α-Glucosidase Inhibitors From Aspergillus terreus ASM-1

2021 ◽  
Vol 9 ◽  
Author(s):  
Changjing Wu ◽  
Xiang Cui ◽  
Luzhen Sun ◽  
Jiajia Lu ◽  
Feng Li ◽  
...  
Keyword(s):  
Aspergillus Terreus ◽  
Exothermic Reaction ◽  
Positive Control ◽  
Postprandial Blood Glucose ◽  
Inhibitory Effects ◽  
Hydrophobic Force ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Thermodynamic Constants ◽  
Glucosidase Inhibitors

Chemical investigation of Aspergillus terreus ASM-1 fermentation resulted in the isolation of three new prenylated aspulvinones V–X (1–3), together with the previously reported analogs, aspulvinone H (4), J-CR (5), and R (6). Their structures were elucidated by various spectroscopic methods including HRESIMS and NMR, and the absolute configurations of 2 and 3 were determined by ECD comparison. Compounds 1–6 were evaluated for α-glucosidase inhibitory effects with acarbose as positive control. As a result, compounds 1 and 4 exhibited potent α-glucosidase inhibitory activities with IC50 values of 2.2 and 4.6 µM in mixed-type manners. The thermodynamic constants recognized the interaction between inhibitors and α-glucosidase was hydrophobic force-driven spontaneous exothermic reaction. The CD spectra also indicate that the compounds 1 and 4 changed the enzyme conformation. Furthermore, compound 4 significantly suppressed the increases in postprandial blood glucose levels in the C57BL/6J mice.

Effects of Maternal Flaxseed Supplementation on Female Offspring of Diabetic Rats in Serum Concentration of Glucose, Insulin, and Thyroid Hormones

2019 ◽  
Vol 89 (1-2) ◽  
pp. 45-54
Author(s):  
Akemi Suzuki ◽  
André Manoel Correia-Santos ◽  
Gabriela Câmara Vicente ◽  
Luiz Guillermo Coca Velarde ◽  
Gilson Teles Boaventura
Keyword(s):  
Thyroid Hormones ◽  
High Fat Diet ◽  
Female Offspring ◽  
Flaxseed Oil ◽  
Diabetic Rats ◽  
High Fat ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Flaxseed Flour ◽  
Maternal Consumption

Abstract. Objective: This study aimed to evaluate the effect of maternal consumption of flaxseed flour and oil on serum concentrations of glucose, insulin, and thyroid hormones of the adult female offspring of diabetic rats. Methods: Wistar rats were induced to diabetes by a high-fat diet (60%) and streptozotocin (35 mg/kg). Rats were mated and once pregnancy was confirmed, were divided into the following groups: Control Group (CG): casein-based diet; High-fat Group (HG): high-fat diet (49%); High-fat Flaxseed Group (HFG): high-fat diet supplemented with 25% flaxseed flour; High-fat Flaxseed Oil group (HOG): high-fat diet, where soya oil was replaced with flaxseed oil. After weaning, female pups (n = 6) from each group were separated, received a commercial rat diet and were sacrificed after 180 days. Serum insulin concentrations were determined by ELISA, the levels of triiodothyronine (T3), thyroxine (T4) and thyroid-stimulating hormone (TSH) were determined by chemiluminescence. Results: There was a significant reduction in body weight at weaning in HG (−31%), HFG (−33%) and HOG (44%) compared to CG (p = 0.002), which became similar by the end of 180 days. Blood glucose levels were reduced in HFG (−10%, p = 0.044) when compared to CG, and there was no significant difference between groups in relation to insulin, T3, T4, and TSH after 180 days. Conclusions: Maternal severe hyperglycemia during pregnancy and lactation resulted in a microsomal offspring. Maternal consumption of flaxseed reduces blood glucose levels in adult offspring without significant effects on insulin levels and thyroid hormones.

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