scholarly journals Pathophysiological Characteristics of Non-Alcoholic Steatohepatitis-Like Changes in Cholesterol-Loaded Type 2 Diabetic Rats

2018 ◽  
pp. 601-612 ◽  
Author(s):  
Y. TORINIWA ◽  
M. MURAMATSU ◽  
Y. ISHII ◽  
E. RIYA ◽  
K. MIYAJIMA ◽  
...  

Spontaneously Diabetic Torii (SDT) fatty rats, a new obese diabetic model, reportedly presented with features of non-alcoholic steatohepatitis (NASH) after 32 weeks of age. We tried to accelerate the onset of NASH in SDT fatty rats using dietary cholesterol loading and noticed changes in the blood choline level which is expected to be a NASH biomarker. Body weight and biochemical parameters were measured from 8 to 24 weeks of age. At 16, 20, 24 weeks, pathophysiological analysis of the livers were performed. Hepatic lipids, lipid peroxides, and the expression of mRNA related to triglyceride (TG) synthesis, inflammation, and fibrosis were evaluated at 24 weeks. Hepatic fibrosis was observed in SDT fatty rats fed cholesterol-enriched diets (SDT fatty-Cho) from 16 weeks. Furthermore, hepatic lipids and lipid peroxide were significantly higher in SDT fatty-Cho than SDT fatty rats fed normal diets at 24 weeks. Hepatic mRNA expression related to TG secretion decreased in SDT fatty-Cho, and the mRNA expression related to inflammation and fibrosis increased in SDT fatty-Cho at 24 weeks. Furthermore, SDT fatty-Cho presented with increased plasma choline, similar to human NASH. There were no significant changes in the effects of feeding a cholesterol-enriched diet in Sprague-Dawley rats. SDT fatty-Cho has the potential to become a valuable animal model for NASH associated with type 2 diabetes and obesity.

Author(s):  
Nkosinathi Cele ◽  
Sihle Ephraim Mabhida ◽  
Thembeka Nyawo ◽  
Khanyisani Ziqubu ◽  
Sthandiwe Mazibuko-Mbeje ◽  
...  

Erectile dysfunction (ED) due to diabetes mellitus remains difficult to treat despite advances in pharmacotherapeutic approaches in the field. Therefore, this study investigated the erectogenic effect of the methanolic extract of Maytenus procumbens roots on type 2 diabetes in rats. The fructose-streptozotocin model was used to induce type 2 diabetes-linked ED in male rats. The sexually active male Sprague Dawley rats were randomly divided into two major groups; normal group and high fructose fed group for 120 days. After 120 days, the high fructose fed group rats were given a single intraperitoneal injection of a freshly prepared streptozotocin solution (30 mg/kg). The diabetic ED rats were orally administered with the extract at 250 mg/kg, daily for 28 days. The serum, brain and penile tissues were removed for biochemical analysis and protein expression. Increased testosterone level, mounting frequency, reduced blood glucose level and serum fructosamine content was observed after 28 days of treatment in diabetic rats. Methanolic extract also exhibited an inhibitory effect on arginase, AChE, and ACE activities. The crude extract further downregulated proteins PDE-5, RhoA and increased expression of eNOS in the diabetic ED treated rats. The results obtained indicate that the methanolic extract of Maytenus procumbens roots ameliorates erectile dysfunction in type 2 diabetes-induced erectile dysfunction in rats.


Author(s):  
Ada Admin ◽  
Michelle Carey ◽  
Eric Lontchi-Yimagou ◽  
William Mitchell ◽  
Sarah Reda ◽  
...  

Hyperglycemia is a potent regulator of endogenous glucose production (EGP). Loss of this ‘glucose effectiveness’ is a major contributor to elevated plasma glucose concentrations in type 2 diabetes (T2D). ATP-sensitive potassium channels (K<sub>ATP</sub> channels) in the central nervous system (CNS) have been shown to regulate EGP in humans and rodents. We examined the contribution of central K<sub>ATP</sub> channels to glucose effectiveness. Under fixed hormonal conditions (‘pancreatic clamp’ studies), hyperglycemia suppressed EGP by ~50% in both non-diabetic humans and normal Sprague Dawley rats. By contrast, antagonism of K<sub>ATP</sub> channels with glyburide significantly reduced the EGP-lowering effect of hyperglycemia in both humans and rats. Furthermore, the effects of glyburide on EGP and gluconeogenic enzymes in rats were abolished by intracerebroventricular (ICV) administration of the KATP channel agonist diazoxide. These findings indicate that about half of EGP suppression by hyperglycemia is mediated by central K<sub>ATP</sub> channels. These central mechanisms may offer a novel therapeutic target for improving glycemic control in T2D.


2016 ◽  
Vol 2016 ◽  
pp. 1-7 ◽  
Author(s):  
Ying Yu ◽  
Xian-Jie Jia ◽  
Wei-ping Zhang ◽  
Ting-ting Fang ◽  
Jie Hu ◽  
...  

Objective. To investigate the effects of low dose ethanol feeding in diabetic rats and analyze its underlying mechanisms.Methods. Male Sprague-Dawley rats were divided into 4 groups: control (Con), diabetes at 4 weeks (DM4W), diabetes at 8 weeks (DM8W), and EtOH + DM8W. After 8 weeks, hemodynamic parameters were recorded and heart weight/body weight (H/B) and hydroxyproline (Hp) content in myocardium were measured. Morphology of collagen in myocardial tissue was observed with Masson’s trichrome staining method and collagen volume fraction (CVF) was analysed. The mRNA expression of ALDH2 was assessed with Real-Time PCR. The protein expressions of p-JNK and JNK were evaluated using western blot.Results. In contrast to Con group, there was no difference in hemodynamic parameters in DM4W group, but mean arterial pressure and heart rate were decreased in DM8W group, and the ratios of H/B, Hp, and CVF were markedly increased. ALDH2 mRNA expression was decreased, while the ratio of p-JNK/JNK were increased. Compared with DM8W group, the above indexes were improved in EtOH + DM8W group.Conclusion. With low dose ethanol intervention, enhanced ALDH2 expression can antagonize the happening of myocardial fibrosis in diabetic rats, which may be relevant with downregulating the JNK pathway.


Author(s):  
Min Hu ◽  
Fan Du ◽  
Shi Liu

The purpose of this study was to investigate the effects of electroacupuncture at Zusanli acupoint on the enteric neuropathy in diabetic rats. Sprague–Dawley rats were divided into different groups depending on the total electroacupuncture span and frequency. The expression of nitric oxide synthase (nNOS), choline acetyltransferase (CHAT), protein gene product 9.5 (PGP9.5), and doublecortin was significantly decreased in the diabetic group compared with the control group. Long-term electroacupuncture at Zusanli with either high frequency or low frequency could increase the expression levels of nNOS, CHAT, PGP9.5, and doublecortin, and the increase was greater in the high-frequency group. But no obvious changes were seen in the short-term electroacupuncture groups. These results suggest that electroacupuncture at Zusanli can restore the deficiency of enteric neurons in diabetes partly but a comparative long duration of stimuli (6 weeks) is required. The increase of doublecortin may be involved in this positive process.


2017 ◽  
Vol 79 (3) ◽  
Author(s):  
Siti Balkis Budin ◽  
Fatin Farhana Jubaidi ◽  
Siti Nur Farahana Mohd Noor Azam ◽  
Nur Liyana Mohamed Yusof ◽  
Izatus Shima Taib ◽  
...  

Previous studies found that Kelulut Honey produced by Trigona spp. bees is able to prevent oxidative damage in various pathological conditions.  Thus, the present study aimed to determine whether Kelulut Honey could prevent the sperm and testicular damage in streptozotocin-induced diabetic rats. Male Adult male Sprague-Dawley rats were divided into four groups: Non-Diabetic (NDM), Non-Diabetic with Kelulut Honey supplementation (NDMKH), Diabetic without supplementation (DM) and Diabetic with Kelulut Honey supplementation (DMKH).  Kelulut honey was given at the dose of 2.0 g/kg weight daily via gavage for 28 consecutive days. Results showed that sperm quality produced by diabetic rats supplemented with Kelulut honey significantly improved compared to the diabetic control groups (p<0.05). SOD activity and GSH level increased significantly (p<0.05) whereas PC and MDA levels significantly decreased in sperm and testis of DMKH rats when compared to DM rats (p<0.05). Histological observation showed obvious increase in spermatozoa in the lumen of epididymis and increased spermatogenic cells density in the testis of DMKH group.  In conclusion, Kelulut Honey has a potential in preventing the damage of sperm and testis in diabetic rats.


2020 ◽  
Author(s):  
Christina Gobin ◽  
Lizhen Wu ◽  
Marek Schwendt

AbstractThe delayed match-to-sample task (DMS) is used to probe working memory (WM) across species. While the involvement of the PFC in this task has been established, limited information exists regarding the recruitment of broader circuitry, especially under the low- versus high-WM load. We sought to address this question by using a variable-delay operant DMS task. Male Sprague-Dawley rats were trained and tested to determine their baseline WM performance across all (0-24s) delays. Next, rats were tested in a single DMS test with either 0s or 24s fixed delay, to assess low-/high-load WM performance. c-Fos mRNA expression was quantified within cortical and subcortical regions and correlated with WM performance. High WM load upregulated overall c-Fos mRNA expression within the PrL, as well as within a subset of mGlu5+ cells, with load-dependent, local activation of protein kinase C as the proposed underlying molecular mechanism. The PrL activity negatively correlated with choice accuracy during high load WM performance. A broader circuitry, including several subcortical regions, was found to be activated under low and/or high load conditions. These findings highlight the role of mGlu5 and/or PKC dependent signaling within the PrL, and corresponding recruitment of subcortical regions during high-load WM performance.


2006 ◽  
Vol 291 (1) ◽  
pp. F49-F57 ◽  
Author(s):  
Swasti Tiwari ◽  
Randall K. Packer ◽  
Xinqun Hu ◽  
Yoshihisa Sugimura ◽  
Joseph G. Verbalis ◽  
...  

Previously, we demonstrated that rats undergoing vasopressin escape had increased mean arterial blood pressure (MAP), plasma and urine aldosterone, and increased renal protein abundance of the α-subunit of the epithelial sodium channel (ENaC), the thiazide-sensitive Na-Cl cotransporter (NCC), and the 70-kDa band of γ-ENaC (Song J, Hu X, Khan O, Tian Y, Verbalis JG, and Ecelbarger CA. Am J Physiol Renal Physiol 287: F1076–F1083, 2004; Ecelbarger CA, Knepper MA, and Verbalis JG. J Am Soc Nephrol 12: 207–217, 2001). Here, we determine whether changes in these renal proteins and MAP require elevated aldosterone levels. We performed adrenalectomies (ADX) or sham surgeries on male Sprague-Dawley rats. Corticosterone and aldosterone were replaced to clamp these hormone levels. MAP was monitored by radiotelemetry. Rats were infused with 1-deamino-[8-d-arginine]-vasopressin (dDAVP) via osmotic minipumps (5 ng/h). At day 3 of dDAVP infusion, seven rats in each group were offered a liquid diet [water load (WL)] or continued on a solid diet (SD). Plasma aldosterone and corticosterone and urine aldosterone were increased by WL in sham rats. ADX-WL rats escaped, as assessed by early natriuresis followed by diuresis; however, urine volume and natriuresis were somewhat blunted. WL did not reduce the abundance or activity of 11-β-hydroxsteroid dehydrogenase type 2. Furthermore, the previously observed increase in renal aldosterone-sensitive proteins and escape-associated increased MAP persisted in clamped rats. The densitometry of immunoblots for NCC, α- and γ-70 kDa ENaC, respectively, were (% sham-SD): sham-WL, 159, 278, 233; ADX-SD, 69, 212, 171; ADX-WL, 116, 302, 161. However, clamping corticosteroids blunted the rise at least for NCC and γ-ENaC (70 kDa). Overall, the increase in aldosterone observed in vasopressin escape is not necessary for the increased expression of NCC, α- or γ-ENaC or increased MAP associated with “escape.”


2018 ◽  
Vol 2018 ◽  
pp. 1-9
Author(s):  
Zhong-Xia Lu ◽  
Wen-Jun Xu ◽  
Yang-Sheng Wu ◽  
Chang-Yu Li ◽  
Yi-Tao Chen

The aim of the present study was to identify key antidiabetic nodes in the livers of pioglitazone-treated type 2 diabetes mellitus Sprague-Dawley rats by transcriptomic and proteomic analysis. Rats were randomly divided into the control, the diabetes model, and the pioglitazone-treated groups. After treatment with pioglitazone for 11 weeks, the effects on fasting blood glucose, body weight, and blood biochemistry parameters were evaluated. Microarray and iTRAQ analysis were used to determine the differentially expressed genes/proteins in rat livers. 1.5-fold changes in gene expression and 1.2-fold changes in protein were set as the screening criteria. After treatment with pioglitazone for 11 weeks, fasting blood glucose in pioglitazone-treated rats was significantly lower than that in the model group. There was a tendency for pioglitazone to reduce TC, TG, TP, ALB, BUN, and HDL-c levels. Kyoto Encyclopedia of Genes and Genomes (KEGG) and gene ontology (GO) were applied to analyze differentially expressed genes/proteins. Furthermore, Western blotting and RT-qPCR were used to validate the results of microarray and iTRAQ. In conclusion, Cyp7a1, Cp, and RT1-EC2 are differentially expressed genes/proteins since they showed a similar trend in rats in the model group and the pioglitazone-treated group.


Author(s):  
Wusa Makena ◽  
Abdullahi Ibrahim Iliya ◽  
Joseph Olajide Hambolu ◽  
James Abrak Timbuak ◽  
Uduak Emmanuel Umana ◽  
...  

Type 2 diabetes (T2D) occur as a result of insulin resistance and malfunction in insulin signaling. Controlling hyperglycemia and activation of insulin signaling are important in the management of T2D. The study aimed to evaluate the effect of Genistein and Momordica charantia L. fruit on oxidative stress, markers of inflammation, and their role on proglucagon and insulin receptor mRNA expression by RT-PCR in diabetic rats. Thirty-five albino rats were divided into seven groups (n=5). Group I (non-diabetic) and group II (diabetic control) were treated with distilled water, groups III and IV received 250mg/kg and 500mg/kg lyophilized MCF respectively. Groups V and VI received 10mg/kg and 20mg/kg Genistein respectively while group VII received 500mg/kg Metformin. The administration lasted for 28 days. MCF and Genistein significantly reduced IL-1β and TNFα levels that was elevated in serum of diabetic rats. Treatment with MCF and Genistein significant increased the expression of proglucagon mRNA in the small intestine and insulin receptor mRNA in the liver of diabetic rats. In conclusion, MCF and Genistein ameliorate type 2 diabetes complications by preventing the loss of insulin-positive cells, inhibiting IL-1β and TNFα and up-regulating proglucagon and insulin receptor mRNA expression. Novelty: • MCF and Genistein has an inhibitory effect on diabetic induced IL-1β and TNFα production. • MCF and Genistein up-regulates proglucagon and insulin receptor mRNA expression.


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