scholarly journals Nutrient Induced Type 2 and Chemical Induced Type 1 Experimental Diabetes Differently Modulate Gastric GLP-1 Receptor Expression

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Olga Bloch ◽  
Efrat Broide ◽  
Gilad Ben-Yehudah ◽  
Dror Cantrell ◽  
Haim Shirin ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Experimental Diabetes ◽  
High Energy ◽  
Diabetic Rats ◽  
Receptor Expression ◽  
Glandular Stomach ◽  
Gastric Glands ◽  
Sd Rats ◽  
Neck Area

T2DM patients demonstrate reduced GLP-1 receptor (GLP-1R) expression in their gastric glands. Whether induced T2DM and T1DM differently affect the gastric GLP-1R expression is not known. This study assessed extrapancreatic GLP-1R system in glandular stomach of rodents with different types of experimental diabetes. T2DM and T1DM were induced inPsammomys obesus(PO) by high-energy (HE) diet and by streptozotocin (STZ) in Sprague Dawly (SD) rats, respectively. GLP-1R expression was determined in glandular stomach by RT PCR and immunohistomorphological analysis. The mRNA expression and cellular association of the GLP-1R in principal glands were similar in control PO and SD rats. However, nutrient and chemical induced diabetes resulted in opposite alterations of glandular GLP-1R expression. Diabetic PO demonstrated increased GLP-1R mRNA expression, intensity of cellular GLP-1R immunostaining, and frequency of GLP-1R positive cells in the neck area of principal glands compared with controls. In contrast, SD diabetic rats demonstrated decreased GLP-1 mRNA, cellular GLP-1R immunoreactivity, and frequency of GLP-1R immunoreactive cells in the neck area compared with controls. In conclusion, nutrient and chemical induced experimental diabetes result in distinct opposite alterations of GLP-1R expression in glandular stomach. These results suggest that induced T1DM and T2DM may differently modulate GLP-1R system in enteropancreatic axis.

scholarly journals The Role of Epoxyeicosatrienoic Acids in Diabetes Mellitus-Induced Impaired Vascular Relaxation of Aortic Rings in Ovariectomized Sprague-Dawley Rats

2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
Dragan Manojlović ◽  
Ana Stupin ◽  
Anita Matić ◽  
Zrinka Mihaljević ◽  
Sanja Novak ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 1 Diabetes ◽  
Mrna Expression ◽  
Vascular Function ◽  
Diabetic Rats ◽  
Ovariectomized Rats ◽  
Aortic Tissue ◽  
Sprague Dawley ◽  
Sd Rats

Aim. The present study was aimed at determining if type 1 diabetes mellitus (DM) affects vascular function and at elucidating the mechanisms mediating vasorelaxation in both nonovariectomized and ovariectomized Sprague-Dawley (SD) rats. Materials and Methods. Eighty female SD rats were divided into four groups: nonovariectomized healthy (non-OVX-CTR) and diabetic (non-OVX-DM) rats and ovariectomized healthy (OVX-CTR) and diabetic (OVX-DM) rats. Bilateral ovariectomy was performed at the age of 5 weeks, and type 1 DM was induced by streptozotocin at the age of 6 weeks. At the age of 12 weeks, acetylcholine-induced relaxation (AChIR) was assessed in aortic rings in the absence/presence of L-NAME, Indomethacin, and MS-PPOH. Aortic tissue mRNA expression of eNOS, iNOS, COX-1, COX-2, thromboxane synthase 1 (TBXAS1), CYP4A1, CYP4A3, and CYP2J3, as well as plasma oxidative stress, was measured. Results. AChIR did not differ in non-OVX-DM rats compared to non-OVX-CTR ones. AChIR was significantly reduced in the OVX-DM group compared to the OVX-CTR group. MS-PPOH did not reduce AChIR in OVX-DM rats as it did in OVX-CTR ones. CYP4a3 mRNA expression in OVX-DM rats was significantly lower compared to that in the OVX-CTR group. Conclusions. Female sex hormones may protect vasorelaxation in type 1 diabetic rats. Type 1 diabetes impairs vasorelaxation in response to ACh in ovariectomized rats (but not in nonovariectomized rats) by affecting vasorelaxation pathways mediated by EETs.

scholarly journals A Protective Role of Arecoline Hydrobromide in Experimentally Induced Male Diabetic Rats

2015 ◽  
Vol 2015 ◽  
pp. 1-12 ◽  
Author(s):  
Indraneel Saha ◽  
Joydeep Das ◽  
Biswaranjan Maiti ◽  
Urmi Chatterji
Keyword(s):  
Glucose Transporter ◽  
Serum Insulin ◽  
Diabetic Rats ◽  
Receptor Expression ◽  
Cell Regeneration ◽  
Sialic Acid Content ◽  
Glucose Transporter 2 ◽  
Experimentally Induced

Objectives.Arecoline, the most potent and abundant alkaloid of betel nut, causes elevation of serum testosterone and androgen receptor expression in rat prostate, in addition to increase in serum insulin levels in rats, leading to insulin resistance and type 2 diabetes-like conditions. This study investigated the role of arecoline on the reproductive status of experimentally induced type 1 diabetic rats.Methods.Changes in the cellular architecture were analyzed by transmission electron microscopy. Blood glucose, serum insulin, testosterone, FSH, and LH were assayed. Fructose content of the coagulating gland and sialic acid content of the seminal vesicles were also analyzed.Results.Arecoline treatment for 10 days at a dose of 10 mg/kg of body weight markedly facilitatedβ-cell regeneration and reversed testicular and sex accessory dysfunctions by increasing the levels of serum insulin and gonadotropins in type 1 diabetic rats. Critical genes related toβ-cell regeneration, such as pancreatic and duodenal homeobox 1 (pdx-1) and glucose transporter 2 (GLUT-2), were found to be activated by arecoline at the protein level.Conclusion.It can thus be suggested that arecoline is effective in ameliorating the detrimental effects caused by insulin deficiency on gonadal and male sex accessories in rats with type 1 diabetes.

The tyrosine kinase inhibitor crizotinib influences blood glucose and mRNA expression of GLUT4 and PPARs in the heart of rats with experimental diabetes

2020 ◽  
Author(s):  
Katarina Hadova ◽  
Lucia Mesarosova ◽  
Eva Kralova ◽  
Gabriel Doka ◽  
Peter Krenek ◽  
...  
Keyword(s):  
Blood Glucose ◽  
Mrna Expression ◽  
Tyrosine Kinases ◽  
Glucose Transporter ◽  
Kinase Inhibitor ◽  
Experimental Diabetes ◽  
Cardiac Metabolism ◽  
Diabetic Rats ◽  
C Peptide ◽  
Glucose Transporter Glut4

Tyrosine kinases inhibitors (TKIs) may alter glycaemia and may be cardiotoxic with importance in diabetic heart. We investigated the effect of multi-TKI crizotinib after short-term administration on metabolic modulators of the heart of diabetic rats. Experimental diabetes mellitus (DM) was induced by streptozotocin (STZ; 80 mg/kg, i.p.), controls received vehicle (CON). Three days after STZ, crizotinib (STZ+CRI; 25 mg/kg/day p.o.) or vehicle was administered for 7 days. Blood glucose, C-peptide and glucagon were assessed in plasma samples. Receptor tyrosine kinases (RTKs), cardiac glucose transporters and PPARs were determined in rat left ventricle by RT-qPCR method. Crizotinib moderately reduced blood glucose (by 25%, P<0.05) when compared to STZ rats. The drug did not affect levels of C-peptide, an indicator of insulin secretion, suggesting altered tissue glucose utilization. Crizotinib had no impact on cardiac RTKs. However, an mRNA downregulation of insulin-dependent glucose transporter Glut4 in hearts of STZ rats was attenuated after crizotinib treatment. Moreover, crizotinib normalized Ppard and reduced Pparg mRNA expression in diabetic hearts. Crizotinib decreased blood glucose independently of insulin and glucagon. This could be related to changes in regulators of cardiac metabolism such as GLUT4 and PPARs.

scholarly journals Changes in the transcriptional activity of the entero-insular axis genes in streptozotocin-induced diabetes and after the administration of TNF-α non-selective blockers

2020 ◽  
Vol 54 (3) ◽  
pp. 160-171
Author(s):  
Anna S. Degen ◽  
Inna Y. Krynytska ◽  
Aleksandr M. Kamyshnyi
Keyword(s):  
Transcriptional Activity ◽  
Experimental Diabetes ◽  
Quantitative Polymerase Chain Reaction ◽  
Diabetic Rats ◽  
Inflammatory Factors ◽  
Genes Expression ◽  
Tnf Α ◽  
Streptozotocin Induced Diabetes ◽  
Polymerase Chain

AbstractObjective. The aim of the present study was to investigate the transcriptional activity of the GLP-1R, DPP-4, SGLT-1, INSR, and IGF-1R genes in GALT cells of rats with streptozotocin-induced diabetes in both untreated and treated with pentoxifylline, as a non-specific blocker of TNF-α.Methods. The expression of GLP-1R, DPP-4, SGLT-1, INSR, and IGF-1R genes in GALT cells of rats was studied by real time quantitative polymerase chain reaction.Results. It was shown that the development of diabetes was accompanied by the decrease of GLP-1R and an increase of DPP-4 genes expression in rat ileum. The administration of pentoxifyl-line to diabetic animals led to an increase in the transcriptional activity of GLP-1R on the 4th week and decrease in transcriptional activity of DPP-4 on the 2nd and 4th weeks of the experiment. An increase in the normalized expression of SGLT-1 on the 4th week of the experimental diabetes was also noted, while the administration of pentoxifylline to diabetic animals did not lead to significant changes in this index. The transcriptional activity of the INSR and IGF-1R genes was reduced in diabetic rats and the administration of the non-specific TNF-α blocker – pentoxifylline led to a significant increase only for INSR gene in animals on the 4th week of the experimental diabetes.Conclusions. The expression of incretins, glucose transporters, and pro-inflammatory cytokines (e.g. TNF-α) in immune cells may be used as markers of several autoimmune pathologies progression such as type 1 diabetes due to their effect on the balance of pro- and anti-inflammatory factors.

Dynamic Alterations in the Expression of P2Y12 Receptor but Not COX-1 in Platelets from Streptozocin-Induced Diabetic Rats.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2638-2638
Author(s):  
Chi Chen ◽  
Zili He ◽  
Candice Ruby ◽  
Waqas Arslan ◽  
Madhumati Kalavar ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Messenger Rna ◽  
Early Stage ◽  
Diabetic Rats ◽  
Dense Granule ◽  
Receptor Expression ◽  
P2y12 Receptor ◽  
Mrna Levels ◽  
Cyclooxygenase 1 ◽  
Cox 1

Abstract In patients or animals with established diabetes mellitus, platelets have been shown to be hyperreactive to ADP. This alteration of the platelet function occurs independent of activation of the arachidonate pathway or release of dense granule contents. In the present study, we examined the expression of the platelet ADP-binding receptor, P2Y12, in early stage of streptozocin(STZ)-induced diabetes in rats. Platelet messenger RNA (mRNA) levels for P2Y12 and cyclooxygenase-1 (COX-1) were determined by comparative RT-PCR in 7 control rats on day 0, 6 diabetic rats each on days 2, 3, 4, and 4 diabetic rats on day 7 after intraperitoneal injection of streptozocin (50 mg/kg). The plasma glucose level was 406 ± 10 mg/dl in diabetic rats, significantly greater than 151 ± 12 mg/dl in control rats. After induction of diabetes, the expression of P2Y12 mRNA significantly decreased to 76 ± 9% of the level of control on day 2, 54 ± 6% of control on day 3, reached a nadir of 28 ± 6% of control on day 4, and rose to 43 ± 10% of control on day 7. These dynamic changes of P2Y12 mRNA in platelets reflected the expression of P2Y12 mRNA in megakaryocytes isolated to a high state of purity (&gt;96 %) from rat bone marrow. Specifically, the megakaryocytic P2Y12 mRNA expression in the diabetic rats on days 1, 2 and 3 were 74 ± 8 %, 93 ± 1%, and 117 ± 6% of those in control rats, respectively. Treatment of diabetic rats with insulin reduced the trend of decline in the platelet P2Y12 expression. By contrast, the platelet COX-1 mRNA expression measured on days 2, 3, 4 and 7 after the induction of diabetes was similar to that in the control rats. These results in diabetic rats demonstrate dynamic alterations of the mRNA expression of megakaryocyte-platelet P2Y12, but not of COX-1. The decrease in the P2Y12 receptor expression in early stage of STZ-induced diabetes may serve to attenuate the hyperaggregability of platelets and reduce the risk of vascular thrombosis.

scholarly journals Role of peripheral 5-HT5A receptors in 5-HT-induced cardiac sympatho-inhibition in type 1 diabetic rats

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
José Ángel García-Pedraza ◽  
Oswaldo Hernández-Abreu ◽  
Asunción Morán ◽  
José Carretero ◽  
Mónica García-Domingo ◽  
...  
Keyword(s):  
Sympathetic Innervation ◽  
Stellate Ganglion ◽  
Receptor Activation ◽  
Diabetic Rats ◽  
Receptor Expression ◽  
Cardiac Sympathetic Innervation ◽  
Group I ◽  
Male Wistar Rats

Abstract 5-HT inhibits cardiac sympathetic neurotransmission in normoglycaemic rats, via 5-HT1B, 5-HT1D and 5-HT5A receptor activation. Since type 1 diabetes impairs the cardiac sympathetic innervation leading to cardiopathies, this study aimed to investigate whether the serotonergic influence on cardiac noradrenergic control is altered in type 1 diabetic rats. Diabetes was induced in male Wistar rats by streptozotocin (50 mg/kg, i.p.). Four weeks later, the rats were anaesthetized, pithed and prepared for producing tachycardic responses by electrical preganglionic stimulation (C7-T1) of the cardioaccelerator sympathetic outflow or i.v. noradrenaline bolus injections. Immunohistochemistry was performed to study 5-HT1B, 5-HT1D and 5-HT5A receptor expression in the stellate ganglion from normoglycaemic and diabetic rats. In the diabetic group, i) i.v. continuous infusions of 5-HT induced a cardiac sympatho-inhibition that was mimicked by the 5-HT1/5A agonist 5-carboxamidotryptamine (without modifying noradrenaline-induced tachycardia), but not by the agonists indorenate (5-HT1A), CP 93,129 (5-HT1B), PNU 142633 (5-HT1D), or LY344864 (5-HT1F); ii) SB 699551 (5-HT5A antagonist; i.v.) completely reversed 5-CT-induced cardiac sympatho-inhibition; and iii) 5-HT5A receptors were more expressed in the stellate ganglion compared to normoglycaemic rats. These results show the prominent role of the peripheral 5-HT5A receptors prejunctionally inhibiting the cardiac sympathetic drive in type 1 diabetic rats.

PTH-related protein and Type 1 PTH receptor mRNA expression in ventricular myocardial hypertrophy

Therapy ◽  
2005 ◽  
Vol 2 (3) ◽  
pp. 415-423
Author(s):  
Antony Halapas ◽  
Peter Lembessis ◽  
Antigone Sourla ◽  
Costas Pantos ◽  
Dennis V Cokkinos ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Myocardial Hypertrophy ◽  
Related Protein ◽  
Receptor Mrna

Effect of Curcuma longa and Galega orientalis on renal function in rats with experimental diabetes mellitus and acute renal failure

2019 ◽  
pp. 88-95
Author(s):  
Р.И. Айзман ◽  
А.П. Козлова ◽  
Е.И. Гордеева ◽  
М.С. Головин ◽  
Г.А. Корощенко ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Renal Failure ◽  
Renal Function ◽  
Acute Renal Failure ◽  
Experimental Diabetes ◽  
Curcuma Longa ◽  
Diabetic Rats ◽  
Standard Diet ◽  
Experimental Diabetes Mellitus ◽  
Galega Orientalis

Цель - исследование влияния куркумы длинной и галеги восточной на осмо- и ионорегулирующую функции почек крыс при аллоксан-индуцированном сахарном диабете и острой почечной недостаточности в эксперименте. Методика. Эксперименты выполнены на самцах крыс Wistar (n=70) с моделью сахарного диабета (1-я серия) и острой почечной недостаточности (2-я серия). В обеих сериях животные были поделены на 3 группы: крыс 1-й группы содержали на стандартном корме, крысам остальных групп в корм добавляли куркуму (2-я группа) или галегу (3-я группа) (2% от массы корма). На 7-е сут эксперимента проводили исследование диуретической и ионоуретической функций почек натощак и после 5% водной нагрузки. Концентрацию ионов в моче и плазме определяли методом пламенной фотометрии; осмотическую концентрацию биологических жидкостей - методом криоскопии; биохимические показатели крови - колориметрическим методом. Результаты. У животных с сахарным диабетом фоновый диурез, а также экскреция натрия и калия были статистически значимо выше, чем у контрольных животных. При острой почечной недостаточности наблюдался более низкий уровень диуреза и ионоуреза, особенно после водной нагрузки. Прием куркумы и галеги вызывал улучшение осмо- и ионорегулирующей функции почек у крыс с сахарным диабетом, и практически не влиял на эти функции почек при острой почечной недостаточности. Заключение. При сахарном диабете оба фитопрепарата вызывали понижение концентрации глюкозы, креатинина, мочевины и улучшение ионно-осмотических показателей плазмы крови, при этом эффект куркумы был выражен отчетливее. При острой почечной недостаточности эти фитопрепараты не давали описанного эффекта. Aim. To study effects of the phytomedicines, Curcuma longa and Galega orientalis, on osmosis- and ion-regulating renal functions in rats with experimental diabetes mellitus (DM) and acute renal failure (ARF). Methods. Experiments were performed in two series on Wistar male rats (n=70) with modeled diabetes mellitus (series 1) and acute renal failure (series 2). In each series, the animals were divided into 3 groups, 1) rats of group 1 receiving a standard diet; 2) rats of groups 2 and 3 receiving a standard diet supplemented with turmeric or galega (2% of food weight), respectively. On the 7th day of the experiment, the diuretic and ionuretic renal function was studied in fasting state and after 5% water loading. Concentrations of ions in urine and plasma were determined by flame photometry; osmotic concentrations of biological fluids were measured by cryoscopy; blood biochemical parameters were measured by colorimetry. Results. In diabetic rats, background diuresis and sodium and potassium excretion were significantly higher than in the control animals. In rats with acute renal failure, diuresis and ionuresis were significantly lower, particularly after the water loading. Turmeric and galega supplementation improved the osmotic and ion-regulating renal function in diabetic rats and left practically unchanged these functions in rats with acute renal failure. Conclusion. In rats with diabetes mellitus, both herbal remedies reduced concentrations of glucose, creatinine, and urea and improved ion-osmotic parameters of blood plasma with a more pronounced effect of turmeric. In acute renal failure, these phytomedicines did not produce the described effects.

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