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.

scholarly journals Exclusive Peripheral Overexpression of 5-HT5A Receptors is Involved in 5‑HT‑Induced Cardiac Sympatho-Inhibition in Type 1 Diabetic Rats

2020 ◽  
Author(s):  
Jose Ángel Garcia-Pedraza ◽  
Oswaldo Hernández-Abreu ◽  
Asunción Morán ◽  
José Carretero ◽  
Mónica García-Domingo ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Sympathetic Innervation ◽  
Stellate Ganglion ◽  
Cardiovascular Complications ◽  
Diabetic Rats ◽  
Cardiac Autonomic Neuropathy ◽  
Sympathetic Outflow ◽  
Cardiac Sympathetic Innervation ◽  
Pithed Rats

Abstract Background: In normoglycaemic pithed rats, cardiac sympathetic control is modulated by serotonin (5-hydroxytryptamine; 5‑HT), which inhibits the cardioaccelerator sympathetic outflow via the activation of 5-HT 1B , 5-HT 1D and 5-HT 5A receptors. Notwithstanding, type 1 diabetes impairs the functionality of the cardiac sympathetic innervation and leads to cardiovascular complications including cardiac autonomic neuropathy. On this basis, the present study investigated whether the influence of 5-HT on cardiac noradrenergic neurotransmission is altered in type 1 diabetic rats, by analysing the profile of the 5-HT receptors involved and their peripheral expression. Methods: Type 1 diabetes was induced in male Wistar rats with a single injection of streptozotocin (50 mg/kg, i.p.). Four weeks later, the rats were anaesthetized, pithed and prepared for producing tachycardic responses by either electrical preganglionic stimulation (C 7 ‑T 1 ) of the cardioaccelerator sympathetic outflow or i.v. bolus injections of exogenous noradrenaline. Immunohistochemistry analyses were performed to study the expression of 5‑HT 1B , 5-HT 1D and 5-HT 5A receptors in the stellate (sympathetic) ganglion obtained from normoglycaemic and diabetic rats. Results: The increases in heart rate evoked by both cardiac sympathetic stimulation and exogenous noradrenaline were not modified after saline in diabetic rats. Moreover, i.v. continuous infusions of 5‑HT induced a cardiac sympatho-inhibition that was mimicked by the 5‑HT 1/5A receptor agonist 5‑carboxamidotryptamine, but not by the agonists indorenate (5-HT 1A ), CP 93,129 (5‑HT 1B ), PNU 142633 (5-HT 1D ), or LY344864 (5‑HT 1F ) in the diabetic group. In contrast, the above agonists at 5-HT 1B , 5-HT 1D and 5-HT 1/5A receptors mimicked 5-HT-induced sympatho-inhibition in normoglycaemic rats. In diabetic animals, i.v. administration of SB 699551 (1 mg/kg; 5‑HT 5A receptor antagonist) abolished 5‑CT-induced cardiac sympatho-inhibition. Finally, the immunohistochemistry analysis in the stellate ganglion showed that, as compared to normoglycaemic rats, in diabetic rats (P<0.05): (i) the expression of 5-HT 1B receptors was slightly higher, whereas that of 5-HT 1D receptors was slightly lower; and (ii) there was a clear overexpression of 5-HT 5A receptors. Conclusions: Taken together, these results show the prominent role of the peripheral overexpression of prejunctional 5-HT 5A receptors in the inhibition of the cardiac sympathetic drive in type 1 diabetic rats. These findings may represent a new pharmacological strategy for the treatment of diabetes-related cardiac abnormalities.

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.

scholarly journals Effects of Cholecalciferol on Key Components of Vitamin D-Endo/Para/Autocrine System in Experimental Type 1 Diabetes

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Anna Mazanova ◽  
Ihor Shymanskyi ◽  
Olha Lisakovska ◽  
Lala Hajiyeva ◽  
Yulia Komisarenko ◽  
...  
Keyword(s):  
Vitamin D ◽  
Type 1 Diabetes ◽  
Vitamin D Deficiency ◽  
Diabetic Rats ◽  
Hydroxyvitamin D ◽  
Male Wistar Rats ◽  
Experimental Type ◽  
25 Hydroxyvitamin D

Objectives.Recent prospective studies have found the associations between type 1 diabetes (T1D) and vitamin D deficiency. We investigated the role of vitamin D in the regulation of 25OHD-1α-hydroxylase (CYP27B1) and VDR expression in different tissues of T1D rats.Design.T1D was induced in male Wistar rats by streptozotocin (55 mg/k b.w.). After 2 weeks of T1D, the animals were treated orally with or without vitamin D3(cholecalciferol; 100 IU/rat, 30 days).Methods.Serum 25-hydroxyvitamin D (25OHD) was detected by ELISA. CYP27A1, CYP2R1, CYP27B1, and VDR were assayed by RT-qPCR and Western blotting or visualized by immunofluorescence staining.Results.We demonstrated that T1D led to a decrease in blood 25OHD, which is probably due to the established downregulation of CYP27A1 and CYP2R1 expression. Vitamin D deficiency was accompanied by elevated synthesis of renal CYP27B1 and VDR. Conversely, CYP27B1 and VDR expression decreased in the liver, bone tissue, and bone marrow. Cholecalciferol administration countered the impairments of the vitamin D-endo/para/autocrine system in the kidneys and extrarenal tissues of diabetic rats.Conclusions.T1D-induced vitamin D deficiency is associated with impairments of renal and extrarenal CYP27B1 and VDR expression. Cholecalciferol can be effective in the amelioration of diabetes-associated abnormalities in the vitamin D-endo/para/autocrine system.

scholarly journals AMPK activation restores ischemic post-conditioning cardioprotection in STZ-induced type 1 diabetic rats: Role of autophagy

2017 ◽  
Vol 16 (3) ◽  
pp. 3648-3656 ◽  
Author(s):  
Bin Zhou ◽  
Yan Leng ◽  
Shao-Qing Lei ◽  
Zhong-Yuan Xia
Keyword(s):  
Diabetic Rats ◽  
Ampk Activation

scholarly journals HEPATOPROTECTIVE EFFECT OF BANANA PEEL FLOUR ON HISTOLOGICAL AND LIVER FUNCTION IN DIABETIC RATS

2021 ◽  
pp. 529-538
Author(s):  
Herlin Ajeng Nurrahma ◽  
Andreanyta Meliala ◽  
Paramita Narwidina ◽  
Sri Herwiyanti
Keyword(s):  
Liver Function ◽  
Diabetic Rats ◽  
Hepatoprotective Effect ◽  
Banana Peel ◽  
Control Group ◽  
Standard Diet ◽  
Hepatic Enzyme ◽  
Alcoholic Fatty Liver ◽  
Group I ◽  
Male Wistar Rats

In diabetes mellitus, non-alcoholic fatty liver disease (NAFLD) is closely linked to hyperglycemia metabolism. This study aimed to find out how a banana peel supplemented diet affected histological and liver function changes in streptozotocin-induced diabetic rats. Vitamins, minerals, dietary fiber, antioxidants, and tryptophan are all contained in banana peel flour (BPF). Serotonin is a neurotransmitter that has been linked to depression and anxiety. This post-test-only control group study was conducted on twenty-five male Wistar rats which were separated into five groups with different treatments. Groups II to V were diabetic rats model groups that consumed standard diet mixed with BPF 0%, 5%, 10%, and 20%, respectively, while group I was a healthy control group fed a standard diet. Hepatic enzyme transaminase (Alanine Aminotransferase-ALT and Aspartate Aminotransferase - AST) and Hematoxylin-Eosin (HE) staining were analyzed with the NAFLD score to examine the liver function and hepatocellular morphology. A change in liver function was observed, as well as a substantial change in the levels of ALT and AST. The NAFLD score with HE staining showed substantial improvements in liver morphology, which was better seen at a 20% BPF dose. The current study supported the hypothesis that BPF had a hepatoprotective effect in diabetic rats, which may be due to the mechanism of controlling the hepatic enzyme transaminase and inducing liver regeneration.

scholarly journals The Effect of Induced Diabetes Mellitus on the Cerebellar Cortex of Adult Male Rat and the Possible Protective Role of Oxymatrine: A Histological, Immunohistochemical and Biochemical Study

2021 ◽  
Author(s):  
Amany Mohamed Shalaby ◽  
Adel Mohamed Aboregela ◽  
Mohamed Ali Alabiad ◽  
Mona Tayssir Sadek
Keyword(s):  
Diabetes Mellitus ◽  
Purkinje Cells ◽  
Cerebellar Cortex ◽  
Adult Male ◽  
Protective Role ◽  
Diabetic Rats ◽  
Male Rats ◽  
Group I ◽  
Group Ii

Abstract Diabetes mellitus (DM) represents a widespread metabolic disease with a well-known neurotoxicity in both central and peripheral nervous systems. Oxymatrine is a traditional Chinese herbal medicine that has various pharmacological activities including; anti-oxidant, anti-apoptotic and anti-inflammatory potentials. The present work aimed to study the impact of diabetes mellitus on the cerebellar cortex of adult male albino rat and to evaluate the potential protective role of oxymatrine using different histological methods. Fifty-five adult male rats were randomly divided into three groups: group I served as control, group II was given oxymatrine (80 mg/kg/day) orally for 8 weeks and group III was given a single dose of streptozotocin (50mg/kg) intaperitoneally to induce diabetes. Then diabetic rats were subdivided into two subgroups: subgroup IIIa that received no additional treatment and subgroup IIIb that received oxymatrine similar to group II. The diabetic group revealed numerous changes in the Purkinje cell layer in the form of multilayer arrangement of Purkinje cells, shrunken cells with deeply stained nuclei as well as focal loss of the Purkinje cells. A significant increment in GFAP and synaptophysin expression was reported. Transmission electron microscopy showed irregularity and splitting of myelin sheaths in the molecular layer, dark shrunken Purkinje cells with ill-defined nuclei, dilated Golgi saccules and dense granule cells with irregular nuclear outlines in the granular layer. In contrast, these changes were less evident in diabetic rats that received oxymatrine. In conclusion, Oxymatrine could protect the cerebellar cortex against changes induced by DM.

The protective role of alpha-lipoic acid on long-term exposure of rats to the combination of chlorpyrifos and deltamethrin pesticides

2016 ◽  
Vol 33 (2) ◽  
pp. 159-170 ◽  
Author(s):  
Chidiebere Uchendu ◽  
Suleiman F Ambali ◽  
Joseph O Ayo ◽  
King AN Esievo
Keyword(s):  
Lipoic Acid ◽  
Lethal Dose ◽  
Liver Homogenate ◽  
Experimental Period ◽  
Protective Role ◽  
Serum Glucose ◽  
Group I ◽  
Male Wistar Rats

The study was aimed at evaluating the protective role of α-lipoic acid (ALA) on long-term exposure of rats to the combination of chlorpyrifos (CPF) and deltamethrin (DLT). Forty-two (42) male Wistar rats were divided into 6 exposure groups with 7 animals in each group: (I) soya oil (2 ml kg−1), (II) ALA (60 mg kg−1), (III) DLT (6.25 mg kg−1), (IV) CPF (4.75 mg kg−1), (V) (CPF + DLT) DLT (6.25 mg kg−1) and CPF (4.75 mg kg−1; 1/20th of the previously determined median lethal dose) and (VI) (ALA + CPF + DLT) pretreated with ALA (60 mg kg−1) and then co-exposed to CPF and DLT, 45 min later. The regimens were administered by gavage once daily for a period of 16 weeks. Sera obtained from blood collected at the end of the experimental period were used for the evaluation of serum glucose, total protein, albumin, urea, creatinine and the activities of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, lactate dehydrogenase and acetylcholinesterase. The liver homogenate was used to assay for the activities of superoxide dismutase and glutathione peroxidase and the concentrations of malondialdehyde, cytokine and tumour necrotic factor α. The result showed that the combination of CPF and DLT resulted in marked alterations of these biochemical parameters in most cases compared to either of the pesticides singly, supplementation with ALA ameliorated these alterations.

Reduced renal dopamine D1 receptor function in streptozotocin-induced diabetic rats

2004 ◽  
Vol 286 (3) ◽  
pp. F451-F457 ◽  
Author(s):  
Aditi Marwaha ◽  
Anees Ahmad Banday ◽  
Mustafa F. Lokhandwala
Keyword(s):  
Atpase Activity ◽  
Sodium Excretion ◽  
Type I Diabetes ◽  
Receptor Activation ◽  
Diabetic Rats ◽  
D1 Receptor ◽  
Skf 38393 ◽  
Receptor Expression ◽  
Type I ◽  
Renal Dopamine

Dopamine, via activation of renal D1 receptors, inhibits the activities of Na-K-ATPase and Na/H exchanger and subsequently increases sodium excretion. Decreased renal dopamine production and sodium excretion are associated with type I diabetes. However, it is not known whether the response to D1 receptor activation is altered in type I diabetes. The present study was designed to examine the effect of streptozotocin-induced type I diabetes on renal D1 receptor expression and function. Streptozotocin treatment of Sprague-Dawley rats caused a fourfold increase in plasma levels of glucose along with a significant decrease in insulin levels compared with control rats. Intravenous administration of SKF-38393, a D1 receptor agonist, caused a threefold increase in sodium excretion in control rats. However, SKF-38393 failed to produce natriuresis in diabetic rats. SKF-38393 caused a concentration-dependent inhibition of Na-K-ATPase activity in renal proximal tubules of control rats. However, the ability of SKF-38393 to inhibit Na-K-ATPase activity was markedly diminished in diabetic rats. D1 receptor numbers and protein abundance as determined by [3H]SCH-23390 ligand binding and Western blot analysis were markedly reduced in diabetic rats compared with control rats. Moreover, SKF-38393 failed to stimulate GTPγS binding in proximal tubular membranes from diabetic rats compared with control rats. We conclude that the natriuretic response to D1 receptor activation is reduced in type I diabetes as a result of a decrease in D1 receptor expression and defective receptor G protein coupling. These abnormalities may contribute to the sodium retention associated with type I diabetes.

scholarly journals The Therapeutic Effect of Active Vitamin D Supplementation in Preventing the Progression of Diabetic Nephropathy in a Diabetic Mouse Model

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Nakhoul Nakhoul ◽  
Tina Thawko ◽  
Evgeny Farber ◽  
Inbal Dahan ◽  
Hagar Tadmor ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Vitamin D ◽  
Diabetic Nephropathy ◽  
Vitamin D Receptor ◽  
Receptor Activation ◽  
Receptor Expression ◽  
Active Vitamin ◽  
Active Vitamin D ◽  
Vitamin D Analog

Background. Diabetic nephropathy (DN) is one of the most common microvascular complications of diabetes and is the leading cause of end-stage renal disease (ESRD) and replacement therapy worldwide. Vitamin D levels in DN patients are very low due to the decrease in the synthesis and activity of 1-α hydroxylase in the proximal tubule cells and decrease in the vitamin D receptor abundance. To date, few studies have shown the antioxidant effects of 1α,25-dihydroxyvitamin D3 [1,25(OH)2D3] on hyperglycemia-induced renal injury. The selective activator of the vitamin D receptor, paricalcitol, reduces proteinuria and slows the progression of kidney injury. The precise mechanism through which vitamin D affects diabetic status and provides kidney protection remains to be determined. Methods. Diabetes mellitus (DM) was induced in 94 8-week-old DBA/2J mice by intraperitoneal injection of streptozotocin (STZ). DM mice were randomly divided into receiving vehicle or treatment with paricalcitol, the active vitamin D analog, 1 week after DM induction or paricalcitol treatment 3 weeks after DM induction. An additional control group of healthy wild-type mice was not treated. Urine albumin, blood urea nitrogen, and creatinine levels were measured before and at the end of the paricalcitol treatment. Periodic acid-Schiff, immunohistochemistry staining, and western blot of the renal tissues of vitamin D receptor, villin, nephrin, and podocin expressions, were analyzed. Results. Paricalcitol treatment restored villin, nephrin, and podocin protein levels that were downregulated upon DM induction, and reduced fibronectin protein level. Vitamin D receptor activation by paricalcitol may reduce proteinuria of DN in mice and alleviate high-glucose-induced injury of kidney podocytes by regulating the key molecules such nephrin-podocin. Conclusions. Paricalcitol treatment was associated with improved structural changes in type 1 diabetic mice including upregulation of vitamin D receptor expression, and decreased fibrosis markers such as fibronectin. These effects may contribute to the consistent benefit of vitamin D analog to slow the deterioration in glomerular function and reduce the risk of ESRD in patients with type 1 and 2 diabetes mellitus. Our results suggest that additional use of paricalcitol may be beneficial in treating patients with diabetes under standard therapeutic strategies.

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