scholarly journals Euglycemia in Diabetic Rats Leads to Reduced Liver Weight via Increased Autophagy and Apoptosis through Increased AMPK and Caspase-3 and Decreased mTOR Activities

2015 ◽  
Vol 2015 ◽  
pp. 1-12 ◽  
Author(s):  
Jun-Ho Lee ◽  
Soo-Bong Choi ◽  
Mingli Jin ◽  
Ju-Han Lee ◽  
Sang-Don Han ◽  
...  

Euglycemia is the ultimate goal in diabetes care to prevent complications. However, the benefits of euglycemia in type 2 diabetes are controversial because near-euglycemic subjects show higher mortality than moderately hyperglycemic subjects. We previously reported that euglycemic-diabetic rats on calorie-control lose a critical liver weight (LW) compared with hyperglycemic rats. Here, we elucidated the molecular mechanisms underlying the loss of LW in euglycemic-diabetic rats and identified a potential risk in achieving euglycemia by calorie-control. Sprague-Dawley diabetic rats generated by subtotal-pancreatectomy were fed a calorie-controlled diet for 7 weeks to achieve euglycemia using 19 kcal% (19R) or 6 kcal% (6R) protein-containing chow or fedad libitum(19AL). The diet in both R groups was isocaloric/kg body weight to the sham-operated group (19S). Compared with 19S and hyperglycemic 19AL, both euglycemic R groups showed lower LWs, increased autophagy, and increased AMPK and caspase-3 and decreased mTOR activities. Though degree of insulin deficiency was similar among the diabetic rats, Akt activity was lower, and PTEN activity was higher in both R groups than in 19AL whose signaling patterns were similar to 19S. In conclusion, euglycemia achieved by calorie-control is deleterious in insulin deficiency due to increased autophagy and apoptosis in the liver via AMPK and caspase-3 activation.

2017 ◽  
Vol 42 (2) ◽  
pp. 181-192 ◽  
Author(s):  
Mohamed M. Amin ◽  
Mahmoud S. Arbid

Even though ellagic acid has previously been valued in many models of cancer, so far its full mechanistic effect as a natural antiapoptotic agent in the prevention of type 2 diabetes complications has not been completely elucidated, which was the goal of this study. We fed albino rats a high-fat fructose diet (HFFD) for 2 months to induce insulin resistance/type 2 diabetes and then treated the rats with ellagic acid (10 mg/kg body weight, orally) and/or repaglinide (0.5 mg/kg body weight, orally) for 2 weeks. At the serum level, ellagic acid challenged the consequences of HFFD, significantly improving the glucose/insulin balance, liver enzymes, lipid profile, inflammatory cytokines, redox level, adipokines, ammonia, and manganese. At the tissue level (liver, pancreas, adipose tissue, and brain), ellagic acid significantly enhanced insulin signaling, autophosphorylation, adiponectin receptors, glucose transporters, inflammatory mediators, and apoptotic markers. Remarkably, combined treatment with both ellagic acid and repaglinide had a more pronounced effect than treatment with either alone. These outcomes give new insight into the promising molecular mechanisms by which ellagic acid modulates numerous factors induced in the progression of diabetes.


Endocrinology ◽  
2010 ◽  
Vol 151 (4) ◽  
pp. 1588-1597 ◽  
Author(s):  
Andrew C. Shin ◽  
Huiyuan Zheng ◽  
R. Leigh Townsend ◽  
David L. Sigalet ◽  
Hans-Rudolf Berthoud

Roux-en-Y gastric bypass (RYGB) surgery is the most effective treatment for morbid obesity and remission of associated type 2 diabetes, but the mechanisms involved are poorly understood. The aim of the present study was to develop and validate a rat model for RYGB surgery that allows repeated measurement of meal-induced changes in gut and pancreatic hormones via chronic venous catheters. Male Sprague Dawley rats made obese on a palatable high-fat diet were subjected to RYGB or sham surgery and compared with chow-fed, lean controls. Hormonal responses to a mixed-liquid test meal were examined by frequent blood sampling through chronically implanted jugular catheters in freely behaving rats, 3–4 months after surgery, when RYGB rats had significantly reduced body weight and fat mass compared with sham-operated rats. Hyperleptinemia, basal hyperinsulinemia, and hyperglycemia as well as postprandial glucose intolerance seen in sham-operated, obese rats were completely reversed by RYGB and no longer different from lean controls. Postprandial increases in glucagon-like peptide-1, peptide YY, and amylin as well as suppression of ghrelin levels were all significantly augmented in RYGB rats compared with both sham-operated obese and lean control rats. Thus, our rat model replicates most of the salient hormonal and glycemic changes reported in obese patients after RYGB, with the addition of amylin to the list of potential candidate hormones involved in hypophagia, weight loss, and remission of diabetes. The model will be useful for elucidating the specific peripheral and central mechanisms involved in the suppression of appetite, loss of body weight, and remission of type 2 diabetes.


2020 ◽  
Vol 1 (1) ◽  
Author(s):  
Ni Wayan Desi Bintari ◽  
Putu Ayu Parwati

Type 2 Diabetes Mellitus (T2DM) is the more common type of diabetes results from the ineffective use of insulin. Improvement of the metabolic system in T2DM patients can be done through the regulation of gut microbiota balance. Gut microbial improvement can be modulated directly by probiotic food consumption. Soygurt is probiotic food with a low glycemic index (GI) and glycemic load (GL) value and rich in isoflavones, which has a potential effect in reducing diabetes risk. The aim of this study is to determine the effect of soygurt consumption in blood glucose levels and body weight of albino wistar rats (Rattus norvegitus). Reseach using a completely randomized design for experimental study. Subjects of this research are 30 male rats (R. norvegistus) aged 2-3 months with average body weight 150-200 gr. Diabetic rats were induced by using single intraperitoneal injection (175 mg/kg BW) alloxan monohydrate. Soygurt feeding given once daily using oral gavage feeding. The result showed that soygurt feeding in diabetic rats with three variations of treatment could significantly (p<0,05), lowering blood sugar level and improve body weight after 28 days of treatment. Treatment of 4ml/day soygurt has the highest effect in lowering blood sugar level and improving body weight, followed by treatment of 3ml/day and 2ml/day soygurt.


2009 ◽  
Vol 296 (4) ◽  
pp. E765-E774 ◽  
Author(s):  
Susan Reinwald ◽  
Richard G. Peterson ◽  
Matt R. Allen ◽  
David B. Burr

The incidence and prevalence of type 2 diabetes (T2D) continue to escalate at an unprecedented rate in the United States, particularly among populations with high rates of obesity. The impact of T2D on bone mass, geometry, architecture, strength, and resistance to fracture has yet to be incontrovertibly characterized because of the complex and heterogeneous nature of this disease. This study utilized skeletally mature male diabetic rats of the commonly used Zucker diabetic fatty (ZDF) and Zucker diabetic Sprague-Dawley (ZDSD) strains as surrogate models to assess alterations in bone attributable to T2D-like states. After the animals were euthanized, bone data were collected using dual-energy X-ray absorptiometry, peripheral quantitative tomography, and micro-CT imaging modalities and via three-point bending or compression mechanical testing methods. ZDF and ZDSD diabetic rats exhibited lower bone mineral densities, which coincided with declines in structural strength and increased fragility at the femoral midshaft and the L4 vertebral body in response to monotonic loading. Vertebral trabecular morphology was compromised in both diabetic rodent strains, and ZDSD diabetic rats exhibited additional phenotypic impairments to bone material properties at the spine. Because the metabolic origin of the T2D-like state that develops in the ZDSD rat strain is highly relevant to adult-onset diabetes, it is a particularly attractive novel model for future preclinical research.


2020 ◽  
Vol 2020 ◽  
pp. 1-6 ◽  
Author(s):  
Wenzhuo Zhang ◽  
Jason Widjaja ◽  
Libin Yao ◽  
Yong Shao ◽  
Xiaocheng Zhu ◽  
...  

Background. Although sleeve gastrectomy results in good weight loss and metabolic improvements, it is an irreversible procedure. Therefore, we attempted to assess the possibility of creating a sleeved stomach without resection. Material and Methods. A total of 22 male Sprague-Dawley rats with type 2 diabetes were randomly assigned into 3 different groups: (1) sleeve gastroplasty with gastric remnant-jejunal anastomosis (SGP, n=8); (2) sleeve gastrectomy (SG, n=8); and (3) SHAM (n=6). Body weight, food intake, fasting blood glucose (FBG), hormonal analysis, and oral glucose tolerance test (OGTT) were performed and measured preoperatively and postoperatively. Results. During the postoperative period, SGP and SG showed significantly lower food intake and body weight when compared with the preoperative levels, respectively (p value < 0.05). Postoperatively, SGP and SG showed improvements in FBG and glucose tolerance levels compared to their respective preoperative levels (p<0.05). FBG and glucose tolerance levels did not differ between SGP and SG postoperatively. SG resulted in a reduction in fasting ghrelin levels when compared with the preoperative level (p<0.05). Fasting insulin levels did not differ preoperatively and postoperatively among all groups. Postoperatively, fasting GLP-1 levels were higher in SGP and SG when compared with the preoperative levels, but no statistical significance was observed. Compared preoperatively, the SGP and SG procedures resulted in a decline in HOMA-IR at postoperative 6th week (p<0.05). Conclusion. Our animal experiment suggested that at least in the short term, sleeved stomach without resection resulted in similar weight loss and improved glucose control effects compared to sleeve gastrectomy.


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.


2020 ◽  
Vol 5 (5) ◽  
pp. 185-191
Author(s):  
A. A. Solovyuk ◽  

The determination of molecular mechanisms, genetic control pathways, and modeling of apoptotic processes are necessary for understanding the pathogenesis of type 2 diabetes mellitus, especially in combination with obesity and excess body weight, which in the future may create prerequisites for the search for pathogenetic treatment. The purpose of the study was to assess the state of apoptosis processes in patients with type 2 diabetes mellitus in combination with excess body weight and obesity, depending on the clinical characteristics of the disease. Material and methods. 98 people with diabetes mellitus were examined. The first group consisted of 64 people with excess body weight and obesity (body mass index >25). The second group included 34 people with type 2 diabetes mellitus and normal body weight (body mass index ≤25). The control group consisted of 28 practically healthy individuals, who were comparable to the first and second groups by gender and age. Results and discussion. The presence of type 2 diabetes mellitus, excess body weight and obesity in patients led to increasing the level of the marker of apoptotic death of body cells – caspase-3 by 16.52%. Patients with glycated hemoglobin HbA1c more than 8% showed an increase in caspase-3 compared with patients with compensated diabetes mellitus; the difference was more pronounced in patients with excess body weight and obesity (19.13%, p <0.05). An increase in the duration of type 2 diabetes mellitus led to the activation of apoptosis processes, which was manifested in the rise of the studied apoptosis marker, caspase-3, both in patients with and without obesity (p <0.05). The development of the complication of type 2 diabetes mellitus in obese patients increased caspase-3 levels by 29.04% (p <0.05) in the absence of significant changes in this marker in patients with type 2 diabetes mellitus without obesity. Conclusion. The dynamics of apoptotic processes in patients with type 2 diabetes mellitus combined with and obesity, depending on the clinical characteristics of patients, is closely related to the level of apoptosis marker – caspase of the cysteine proteinase group – caspase-3


Author(s):  
ASHUTOSH KUMAR YADAV ◽  
REETU ◽  
ARUN GARG

Objective: India is the “diabetes capital of the world” with 62.4 million Indians having type 2 diabetes in 2011. A major risk factor for insulin resistance is obesity, which is generally caused by regular physical inactivity and high-fat diet (HFD). Obesity and diabetes are closely related to each other as about 80% of diabetics are obese. Obesity is a common finding in type 2 diabetes. The objective of the study was to investigate the antidiabetic effects of [10]-gingerol in streptozotocin (STZ)- and HFD-induced diabetic rats. Methods: Wistar rats were used for the study. Animals were divided into six groups. The six groups in this study were, Group I (normal control), Group II (diabetic control), Group III (glibenclamide at 5 mg/kg p.o.), Group IV (orlistat at 60 mg/kg p.o.), Group V ([10]-gingerol at 15 mg/kg p.o.), and Group VI [10]-gingerol (30 mg/kg p.o.), respectively. The antidiabetic activity was assessed using blood glucose level, body weight, and various biochemical parameters such as serum total cholesterol (TC) level, triglyceride (TG) level, high-density lipoproteins (HDLs), total protein (TP), serum alanine transaminase, and aspartate aminotransferase (serum glutamic-oxaloacetic transaminase), respectively. Results: [10]-gingerol exhibited an antidiabetic effect by significantly decreased the level of blood glucose, body weight, TC, TG, TP, and increase HDL. The results of the study demonstrated that the treatment with [10]-gingerol significantly (p<0.05) and dose dependently prevented STZ- and HFD-induced diabetic rats. Conclusions: The findings of the study suggest that [10]-gingerol possesses potential antidiabetic activity as it lowers serum glucose level.


2021 ◽  
Author(s):  
Li Zhang ◽  
Ying-juan Huang ◽  
Jia-pan Sun ◽  
Ting-ying Zhang ◽  
Tao-li Liu ◽  
...  

Abstract Background Caloric restriction (CR) has become increasingly attractive in the treatment of type 2 diabetes mellitus (T2DM) because of the increasingly common high-calorie diet and sedentary lifestyle. This study aimed to evaluate the role of CR in T2DM treatment and further explore its potential molecular mechanisms.Methods Sixty male Sprague-Dawley rats were used in this study. The diabetes model was induced by 8 weeks of high-fat diet (HFD) followed by a single dose of streptozotocin injection (30 mg/kg). Subsequently, the diabetic rats were fed HFD at 28 g/day (diabetic control) or 20 g/day (30% CR regimen) for 20 weeks. Meanwhile, normal rats fed a free standard chow diet served as the vehicle control. Body mass, plasma glucose levels, and lipid profiles were monitored. After diabetes-related functional tests were performed, the rats were sacrificed at 10 and 20 weeks, and glucose uptake in fresh muscle was determined. In addition, western blotting and immunofluorescence were used to detect alterations in AKT/AS160/GLUT4 signaling. Results We found that 30% CR significantly attenuated hyperglycemia and dyslipidemia, leading to alleviation of glucolipotoxicity and thus protection of islet function. Insulin resistance was also markedly ameliorated, as indicated by notably improved insulin tolerance and homeostatic model assessment for insulin resistance (HOMA-IR). However, the improvement in glucose uptake in skeletal muscle was not significant. The upregulation of AKT/AS160/GLUT4 signaling in muscle induced by 30% CR also attenuated gradually over time. Interestingly, the consecutive decrease in AKT/AS160/GLUT4 signaling in white adipose tissue was significantly reversed by 30% CR. Conclusion CR (30%) could protect islet function from hyperglycemia and dyslipidemia, and improve insulin resistance. The mechanism by which these effects occurred is likely related to the upregulation of AKT/AS160/GLUT4 signaling.


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