Effect of fermented cassava tuber on the gene expression of PI3K/Akt signaling and AMPK pathway in STZ-NA-induced diabetic rats

2022 ◽  
Vol ahead-of-print (ahead-of-print) ◽  
Author(s):  
Rio Jati Kusuma ◽  
Desty Ervira Puspaningtyas ◽  
Puspita Mardika Sari

Purpose The downstream insulin signaling, such as phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt) pathway, is an important step for skeletal glucose disposal through the translocation of glucose transporter (GLUT)-4. In addition, the master of energy regulator adenosine monophosphate-activated kinase (AMPK) is also involved in GLUT-4 translocation, independent from the PI3K/Akt pathway. Fermented cassava tuber or gatot is a traditional food from Indonesia with antihyperglycemic properties. However, the molecular mechanism leading to this effect is unclear. Therefore, this paper aims to evaluate whether the antidiabetic activity of gatot is through PI3K/Akt dependent or AMPK pathway. Design/methodology/approach Diabetes mellitus was induced in 20 male Wistar rats by intraperitoneal injection of 65 mg/kg body weight streptozotocin and 230 mg/kg body weight nicotinamide. Diabetic rats were randomly allocated into four groups; negative control, positive control (metformin 100 mg/kg body weight), fermented cassava diet replacing 50% of carbohydrate (FC-50) and 100% of carbohydrate (FC-100) in the diet. Serum glucose, insulin and lipid profile were analyzed before and after four weeks of intervention. Genes expression of PI3K subunit alpha, PI3K subunit beta, PI3K regulatory subunit, Akt and AMPK were analyzed using real time polymerase chain reaction (PCR). GLUT-4 protein expression was performed using immunohistochemistry. Findings There is a significant difference (p = 0.000) in serum glucose, insulin, total cholesterol, triglyceride, high density lipoprotein (HDL)-cholesterol and LDL-cholesterol between groups. Skeletal AMPK gene expression was higher and significantly different between FC-100 (p = 0.006) and healthy control groups. No significant difference was observed in the messenger ribonucleic acid (mRNA) expression of the PI3K/Akt pathway among groups. GLUT-4 expression was highly expressed in a positive control group followed by FC-100. Research limitations/implications This paper did not characterize the bioactive component that is responsible for increasing mRNA expression of AMPK. This paper also did not analyze the phosphorylation of PI3K/Akt and AMPK that are important in activating the protein. Originality/value To the best of the authors’ knowledge, this is the first study that showed the antidiabetic activity of traditional fermented food is through AMPK-dependent activity.

2020 ◽  
Vol 16 (1) ◽  
pp. 33-41
Author(s):  
Mohini C. Upadhye ◽  
Uday Deokate ◽  
Rohini Pujari ◽  
Vishnu Thakare

Background: Ficus glomerata (F. glomerata) Linn. Family Moraceace is a large tree found all over India including outer Himalayan ranges, Punjab, Chota Nagpur, Bihar, Orissa, West Bengal, Rajasthan, Deccan and also as a common plant in South India. It is planted around the home and temples. It is cultivated throughout the year, distributed in evergreen forests and moist localities. Objective: The Ethanolic Extract of roots of F. Glomerata (EEFG) belonging to the family Moraceace, was investigated for its antidiabetic activity using alloxan induced diabetic rats. Methods: Thirty rats were divided into 5 groups having 6 rats in each group. The alloxan was administered to the rats of all groups except normal control group through intraperitoneal route at a concentration of 140mg/kg body weight. A dose of 100mg/kg and 200 mg/kg body weight of EEFG was administered to alloxan induced diabetic rats. The administration of the extract was lasted for 11 days. Effectiveness of the extract on glucose, cholesterol, triglycerides, and high density lipoprotein and protein concentrations was analyzed. Results: Significant (p<0.05) reduction in the levels of glucose, cholesterol, triglyceride of the diabetic rats was observed after treatment with ethanolic extract. After subjecting to oral glucose tolerance test EEFG also showed significant improvement in glucose tolerance. Conclusion: F. glomerata root ethanolic extract showed that it possesses antidiabetic effect and can be found useful for the management of diabetes mellitus.


2016 ◽  
Vol 5 (06) ◽  
pp. 4641 ◽  
Author(s):  
Adel Abdel Moneim* ◽  
Sanaa M. Abd El-Twab ◽  
Mohamed B. Ashour ◽  
Ahmed I. Yousef

The goal of diabetes treatment is primarily to save life and alleviate symptoms and secondary to prevent long-term diabetic complications resulting from hyperglycemia. Thus, our present investigation was designed to evaluate the hepato-renal protective effects of gallic acid and p-coumaric acid in nicotinamide/streptozotocin (NA/STZ)-induced diabetic rats. Experimental type 2 diabetes was induced by a single intraperitoneal (i.p.) injection of STZ (65 mg/kg b.wt.), after 15 min of i.p. injection of NA (120 mg/kg b.wt.). Gallic acid and p-coumaric acid were orally administered to diabetic rats at a dose of 20, 40 mg/kg b.wt./day, respectively, for 6 weeks. Body weight, serum glucose, protein profile, liver function enzymes and kidney function indicators was assayed. Treatment with either gallic acid or p-coumaric acid significantly ameliorated the elevated levels of glucose, alanine aminotransferase (ALT), aspartate aminotransferase (AST), urea and uric acid. Both compounds were also found to restore total protein, albumin, and globulin as well as body weight of diabetic rats to near normal values. It can conclude that both gallic acid and p-coumaric acid have potent hypoglycemic and hepato-renal protective effects in diabetic rats. Therefore, our results suggest promising hypoglycemic agents that can attenuate the progression of diabetic hepatopathy and nephropathy.


1985 ◽  
Vol 106 (2) ◽  
pp. 225-231 ◽  
Author(s):  
A.-M. Mendes ◽  
R. J. Madon ◽  
D. J. Flint

ABSTRACT Cortisol implants in normal and diabetic rats reduced body weight, adiposity, insulin receptor concentration and both basal and insulin-stimulated rates of lipogenesis in isolated adipocytes, whilst insulin sensitivity was unchanged. In normal but not diabetic rats these changes were accompanied by increased serum glucose and insulin concentrations. In contrast, progesterone implants in normal and diabetic rats increased body weight gain, adiposity, insulin receptor concentration and both basal and insulin-stimulated rates of lipogenesis in adipose tissue, again without affecting insulin sensitivity. Progesterone did not affect serum insulin concentrations in normal or diabetic rats but accelerated the decline in serum glucose concentrations which occurred during an overnight fast in diabetic rats. The results suggest that (1) cortisol inhibits lipogenesis in adipose tissue without affecting insulin sensitivity, (2) cortisol reduces insulin binding in adipose tissue without a requirement for hyperinsulinaemia, which might itself indirectly lead to down-regulation of the insulin receptor, and (3) in diabetic rats progesterone stimulates lipogenesis in adipose tissue without any increase in food intake or serum insulin concentrations suggesting that progesterone may have a direct anabolic role in adipose tissue. J. Endocr. (1985) 106, 225–231


2008 ◽  
Vol 294 (2) ◽  
pp. H859-H866 ◽  
Author(s):  
Istvan Lekli ◽  
Gergo Szabo ◽  
Bela Juhasz ◽  
Samarjit Das ◽  
Manika Das ◽  
...  

The resveratrol-induced cardiac protection was studied in Zucker obese rats. Rats were divided into five groups: group 1, lean control; group 2, obese control (OC); group 3, obese rats treated orally with 5 mg·kg−1·day−1 of resveratrol (OR) for 2 wk; group 4, obese rats received 10% glucose solution ad libitum for 3 wk (OG); and group 5, obese rats received 10% glucose for 3 wk and resveratrol (OGR) during the 2nd and 3rd wk. Body weight, serum glucose, and insulin were measured, and then hearts were isolated and subjected to 30 min of ischemia followed by 120 min of reperfusion. Heart rate, coronary flow, aortic flow, developed pressure, the incidence of reperfusion-induced ventricular fibrillation, and infarct size were measured. Resveratrol reduced body weight and serum glucose in the OR compared with the OC values (414 ± 10 g and 7.08 ± 0.41 mmol/l, respectively, to 378 ± 12 g and 6.11 ± 0.44 mmol/l), but insulin levels were unchanged. The same results were obtained for the OG vs. OGR group. Resveratrol improved postischemic cardiac function in the presence or absence of glucose intake compared with the resveratrol-free group. The incidence of ventricular fibrillation and infarct size was reduced by 83 and 20% in the OR group, and 67 and 16% in the OGR group, compared with the OC and OG groups, respectively. Resveratrol increased GLUT-4 expression and reduced endothelin expression and cardiac apoptosis in ischemic-reperfused hearts in the presence or absence of glucose intake. Thus the protective effect of resveratrol could be related to its direct effects on the heart.


2009 ◽  
Vol 24 (4) ◽  
pp. 251-255 ◽  
Author(s):  
Honório Sampaio Menezes ◽  
Cláudio Galeano Zettler ◽  
Alice Calone ◽  
Jackson Borges Corrêa ◽  
Carla Bartuscheck ◽  
...  

PURPOSE: To compare body weight and length, heart weight and length, heart-to-body weight ratio, glycemia, and morphometric cellular data of offspring of diabetic rats (ODR) and of normal rats (control). METHODS: Diabetes was induced in 3 pregnant Wistar rats, bearing 30 rats, on the 11th day after conception by intraperitoneal injection of 50 mg/kg of streptozotocin. Six normal pregnant Wistar rats, bearing 50 rats, made up the control group. Morphometric data were obtained using a scale for the weight, length, heart and body measurements. Morphometric cellular data were obtained by a computer assisted method applied to the measurements of myocytes. Statistical analysis utilized Student's t-test, ANOVA and Levene test. RESULTS: Control offspring had greater mean body weight and length than offspring of diabetic rats (p < 0.001). Heart weight and length and heart-to-body ratios of newborn rats differed between groups at birth (p < 0.001), but showed no difference at 21 days. Mean nuclei area and perimetric value of the myocytes decrees throughout the first 21 days of life (p < 0.01) in the diabetic group. CONCLUSIONS: Heart hypertrophy on the offspring of diabetic rats at birth was demonstrated by the significant difference between the groups. After the eleventh day, no difference was found, which confirmed regression of cardiomegaly. The significant difference between the first and the 21th day of life, for nuclei area feature, demonstrate regression of cardiac hypertrophy in the offspring of diabetic rats.


2016 ◽  
Vol 2016 ◽  
pp. 1-5 ◽  
Author(s):  
Abdulrahman L. Al-Malki

Postprandial hyperglycemia is a predisposing factor for vascular dysfunction and organ damage.α-glucosidase is a hydrolytic enzyme that increases the glucose absorption rate and subsequently elevates blood glucose levels. Garlic (Allium sativumL.) is a rich source of several phytonutrients, including thiosulfinate (THIO). The aim of this study was to evaluate the ability of THIO, a potent inhibitor of intestinalα-glucosidase, to reduce postprandial blood glucose. Male albino rats were randomly assigned to five different groups (n=10/group). Group 1 served as the control group. Groups 2–5 were injected intraperitoneally with a single dose of streptozotocin (STZ) to induce diabetes. Group 2 comprised untreated diabetic rats. Groups 3 and 4 contained diabetic rats that were given THIO orally (20 mg/kg body weight/day and 40 mg/kg body weight/day, resp.). Group 5 was the positive control having diabetic rats treated orally with acarbose (10 mg/kg body weight/day; positive control). Diabetic rats treated with THIO displayed a significant blood glucose reduction (p<0.001and < 0.01 by analysis of variance, resp.) and a significant elevation in insulin compared with that of untreated rats. THIO is an effective noncompetitive intestinalα-glucosidase inhibitor that promotes hypoglycemic action (p<0.001) in STZ-injected rats. THIO is a promising agent for the management of postprandial hyperglycemia.


2020 ◽  
Author(s):  
Mae Sri Hartati Wahyuning ◽  
Evy - Yulianti ◽  
Sunarti - Sunarti

Abstract Background. Kappaphycus alvarezii (Doty) Doty ex P.C.Silva is a widely used seaweed that has antioxidant and antiglycation activities. The purpose of this study was to examine the ability of active fraction from Kappaphycus alvarezii to decrease glucose level and inhibit glycation process. Methods. This study used bioassay-guided fractionation through three stages of the extraction, partition, and fractionation processes that were monitored using Thin Layer Chromatography and BSA-Glucose test. Inhibition of glycation was known by calculating percentage of inhibition and IC50. Selected active fraction was used for in vivo tests using 24 Wistar male rats. Measurement of glucose levels used GOD-PAP method, while levels of glycated albumin (GA) and Nε- (carboxymethyl) lysine (CML) were measured using ELISA. Analysis of RAGE gene expression used qPCR. Results Glycation test showed a significant difference (p < 0.05) between all treatments. Chloroform extract showed higher percentage of inhibition (62.4 ± 3.45%) with lower IC50 (0.33 ± 0.01 mg/ml) compared to methanol extract (0.52 ± 0.03 mg/ml). Methanol-soluble extracts had a higher percentage of inhibition (51.10 ± 1.64%) with IC50 0.45 ± 0.05 mg/ml compared to methanol-insoluble extract (1.25 ± 0.05 mg/ml). Fraction II had a higher percentage of inhibition (53.37 ± 1.92%) with IC50 0.12 ± 0.01 mg/ml compared to other fractions. Selected active fraction reduced blood glucose by 1.3% and 5.2% and CML levels by 50.6% and 42.4% at concentrations of 0.17 and 0.255 mg/ml in diabetic rats. RAGE gene expression was lower in the diabetic rat groups treated with active fraction compared to untreated diabetic group. Conclusions The active fraction has ability for reducing blood glucose, antiglycation, or reducing CML levels, and RAGE gene expression.


2020 ◽  
Vol ahead-of-print (ahead-of-print) ◽  
Author(s):  
Mahmud Aditya Rifqi ◽  
Stefania Widya Setyaningtyas ◽  
Qonita Rachmah

PurposeWhite tea is an unfermented tea made from young shoots of Camellia sinensis protected from sunlight to avoid polyphenol degradation. White tea contains a high level of polyphenolic compounds known as catechins. Several types of evidence have suggested that tea consumption has benefits in body weight and endurance maintenance. This study was designed to evaluate the effect of white tea on body weight and endurance of animal models.Design/methodology/approachThis research was an intervention design using 20 Wistar white rats (Rattus Norvegicus) in body weight between 150 and 200 g. The rats were randomized into four groups, three groups receiving white tea drink (WTD) with different doses and the other group receiving plain water in equal volume as a control group for four weeks. The forced swim test (FST) was done to measure their struggling capacity, and digital bodyweight to measure the weight.FindingsIntervention (WTD Groups and Control) caused weight gain among except G3 with the highest doses of white tea. The result showed that WTD intake in G3 had a significant difference (p < 0.05) on body weight gain compared to control. The authors found that WTD in a specific dose (G3: 0.22 mg) tends to maintain the body weight of animals (219.2 ± 41.96; 212.6 ± 46.90, respectively), while other doses caused weight gain. WTD also significantly increased the swimming and struggling capacity of rats that represented improvements the endurance along with the test. There was a statistically significant difference in endurance among all groups (p < 0.05).Research limitations/implicationsThe results of this study can be followed as human intervention research as an input for nutritionists and sports scientists to explore the beneficial effect of white tea.Practical implicationsThe results of this study can be followed as human intervention research as an input for nutritionists and sports scientists to explore the beneficial effect of white tea.Originality/valueThis study adds more evidence and information about the advantages of white tea as potential beverages in future healthy lifestyles.


1970 ◽  
Vol 6 (2) ◽  
pp. 105-107
Author(s):  
Mohammad Emdadul Haque ◽  
Quazi Safayetullah ◽  
Monira Ahsan ◽  
Sheikh Nazrul Islam

Hypoglycemic property of four nutraceuticals named - black cumin, garlic, methi and karela has been investigated on an alloxan induced diabetic rat model. Glibenclamide was used as positive control and normal saline was used as negative control. Serum glucose levels of normal and diabetic induced rats were estimated by Glucose Oxidase method using a kit, and it were 4.33 ± 0.43 mmol/L and 8.27 ± 0.45mmol/L respectively. The alloxan induced diabetic rats were grouped into six, which were then treated with the four nutraceuticals and two controls. Treatment was given orally everyday for 28 days. Serum glucose level was analysed every 7 day intervals. It was observed that lowering of glucose level was significant (P = 0.01) for every 7 day treatment period. All of the nutraceuticals reduced the serum glucose level nearly to the normal value within 28 days. The rate of lowering of the glucose level was found to vary with the nutraceuticals. Garlic was found to be most active like the glibenclamide. The next active one was black cumin followed by methi and karela. The study conclude that nutraceuticals possess significant hypoglycemic property. Key words: Hypoglycaemia; Nutraceuticals; Black cumin; Garlic; Methi; Karela. Dhaka Univ. J. Pharm. Sci. 6(2): 105-107, 2007 (December)


2020 ◽  
Vol 2020 ◽  
pp. 1-14 ◽  
Author(s):  
Asra Iftikhar ◽  
Bilal Aslam ◽  
Maryam Iftikhar ◽  
Wafa Majeed ◽  
Mehwish Batool ◽  
...  

Caesalpinia bonduc has been used in herbal medicines for the treatment of a wide range of diseases from decades. The present study has explored the remedial potential and underlying mechanism of polyphenol extract of Caesalpinia bonduc in alloxanized diabetic rats. HPLC/MS analysis confirmed the presence of phenolics in considerable concentrations in Caesalpinia bonduc extract. Administration of different doses (250 and 500 mg/kg) of CPP extract to hyperglycemic rats for 8 weeks restored blood and serum glucose, insulin, glycosylated hemoglobin, leptin, amylin, and carbohydrate metabolizing enzymes level towards normal compared to alloxanized diabetic group. The effect of CPP extract on various genes such as Pdx-1, Ins-1, ngn-3, GLUT-4, and IRS-1 in insulin signaling pathway and Traf-4, Traf-6, and Mapk-8 in MAPK downstream JNK cascade was examined through qRT-PCR to access the core molecular mechanism involved in CPP-induced recovery of diabetes. Results have revealed that CPP extract reduced oxidative stress in pancreatic β cells by restoring free radical scavenging potential, reducing the mRNA expression of Mapk-8, Traf-4, and Traf-6, and increasing the Pdx-1, Ins-1, ngn-3, GLUT-4, and IRS-1 expression ensuing regeneration of β cells and subsequent insulin release from pancreas. The results obtained in this study recommend that CPP extract may be a promising therapeutic restorative agent in the treatment of diabetes mellitus.


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