In vivo effect of Trigonella foenum graecum on the expression of pyruvate kinase, phosphoenolpyruvate carboxykinase, and distribution of glucose transporter (GLUT4) in alloxan-diabetic rats

2006 ◽  
Vol 84 (6) ◽  
pp. 647-654 ◽  
Author(s):  
Sameer Mohammad ◽  
Asia Taha ◽  
Kamal Akhtar ◽  
R.N.K. Bamezai ◽  
Najma Zaheer Baquer

Plasma glucose levels are maintained by a precise balance between glucose production and its use. Liver pyruvate kinase (PK) and phosphoenolpyruvate carboxykinase (PEPCK), 2 key enzymes of glycolysis and gluconeogenesis, respectively, play a crucial role in this glucose homeostasis along with skeletal muscle glucose transporter (GLUT4). In the diabetic state, this balance is disturbed owing to the absence of insulin, the principal factor controlling this regulation. In the present study, alloxan-diabetic animals having high glucose levels of more than 300 mmol/L have been taken and the administration of Trigonella seed powder (TSP) to the diabetic animals was assessed for its effect on the expression of PK and PEPCK in liver and GLUT4 distribution in skeletal muscle of alloxan-diabetic rats. TSP treatment to the diabetic animals resulted in a marked decrease in the plasma glucose levels. Trigonella treatment partially restored the altered expression of PK and PEPCK. TSP treatment also corrected the alterations in the distribution of GLUT4 in the skeletal muscle.

2005 ◽  
Vol 289 (1) ◽  
pp. F186-F193 ◽  
Author(s):  
Mario Schiffer ◽  
Katalin Susztak ◽  
Mollie Ranalletta ◽  
Amanda C. Raff ◽  
Erwin P. Böttinger ◽  
...  

Kidney disease is a major complication of diabetes, and poor glycemic control is associated with the development of diabetic nephropathy. The precise mechanisms that lead to diabetic kidney disease still remain largely unknown and are under current investigation. Because glucose transporters in the kidney play an important role in the local maintenance of intracellular glucose and plasma glucose homeostasis, the tissue distribution and regulation of glucose transporter GLUT8, a new member of the glucose transporter family with important functions in cellular survival, were examined. To understand the normal regulation of GLUT8 expression in response to metabolic signals, fasting and feeding conditions were studied. Additionally, GLUT8 expression was studied using two different models of insulin resistance, GLUT4−/− and db/db mice. GLUT8 was localized to glomerular podocytes and tubular epithelial cells in the distal portion of the nephron. Expression of GLUT8 in the kidney was influenced by plasma glucose levels in vivo. Podocytes in kidneys of diabetic db/db mice express higher levels of GLUT8 compared with nondiabetic db/m mice. Because podocytes play an important role in glomerulosclerosis development and high levels of glucose have been shown to induce apoptotic cell death in various kidney cells, these data may provide further insight into the pathogenesis of glomerulosclerosis and diabetic nephropathy.


2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Giuseppina T. Russo ◽  
Letteria Minutoli ◽  
Alessandra Bitto ◽  
Domenica Altavilla ◽  
Eugenio Alessi ◽  
...  

Long-term administration of 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR) mimics the effects of endurance exercise by activating AMP kinase and by increasing skeletal muscle expression of GLUT4 glucose transporter. AICAR is an intermediate in the purinede novosynthesis, and its tissue concentrations can be increased,in vivo, by low doses of methotrexate (MTX) through the inhibition of the enzyme AICAR transformylase. We report here the first evidence that, in experimental type 2 diabetes, chronic treatment with low doses of MTX increases skeletal muscle GLUT4 expression and improves metabolic control. MTX (0.5 mg/kg body weight) or vehicle was administered intraperitoneally, once a week for 4 weeks, to genetically diabetic female C57BL/KsJ-m+/+Leptdbmice (db+/db+) and their normoglycemic littermates (db+/+m). In thedb+/db+mice, MTX treatment was associated with a ∼2-fold increase in skeletal muscle GLUT4 protein concentration and a >4-fold increase in GLUT4 mRNA expression (P<0.01, all), as compared to vehicle-treated mice; no significant differences were noted in controls. MTX treatment was also associated with a significant reduction of glucose and insulin serum concentrations in diabetic mice (P<0.001), and glucose levels only (P<0.05) in controls. These data indicate a different route to increase skeletal muscle GLUT4 expression, through the potential inhibition of the enzyme AICAR transformylase.


2015 ◽  
Vol 2015 ◽  
pp. 1-6 ◽  
Author(s):  
Elsnoussi Ali Mohamed ◽  
Mariam Ahmad ◽  
Lee Fung Ang ◽  
Mohd. Zaini Asmawi ◽  
Mun Fei Yam

In the present study, a 50% ethanolic extract ofOrthosiphon stamineuswas tested for itsα-glucosidase inhibitory activity.In vivoassays of the extract (containing 1.02%, 3.76%, and 3.03% of 3′hydroxy-5,6,7,4′-tetramethoxyflavone, sinensetin, and eupatorin, resp.) showed that it possessed an inhibitory activity againstα-glucosidase in normal rats loaded with starch and sucrose. The results showed that 1000 mg/kg of the 50% ethanolic extract ofO. stamineussignificantly (P<0.05) decreased the plasma glucose levels of the experimental animals in a manner resembling the effect of acarbose. In streptozotocin-induced diabetic rats, only the group treated with 1000 mg/kg of the extract showed significantly (P<0.05) lower plasma glucose levels after starch loading. Hence,α-glucosidase inhibition might be one of the mechanisms by whichO. stamineusextract exerts its antidiabetic effect. Furthermore, our findings indicated that the 50% ethanolic extract ofO. stamineuscan be considered as a potential agent for the management of diabetes mellitus.


1995 ◽  
Vol 305 (2) ◽  
pp. 465-470 ◽  
Author(s):  
J F Hocquette ◽  
F Bornes ◽  
M Balage ◽  
P Ferre ◽  
J Grizard ◽  
...  

It is well accepted that skeletal muscle is a major glucose-utilizing tissue and that insulin is able to stimulate in vivo glucose utilization in ruminants as in monogastrics. In order to determine precisely how glucose uptake is controlled in various ruminant muscles, particularly by insulin, this study was designed to investigate in vitro glucose transport and insulin-regulatable glucose-transporter protein (GLUT4) in muscle from calf and goat. Our data demonstrate that glucose transport is the rate-limiting step for glucose uptake in bovine fibre strips, as in rat muscle. Insulin increases the rate of in vitro glucose transport in bovine muscle, but to a lower extent than in rat muscle. A GLUT4-like protein was detected by immunoblot assay in all insulin-responsive tissues from calf and goat (heart, skeletal muscle, adipose tissue) but not in liver, brain, erythrocytes and intestine. Unlike the rat, bovine and goat GLUT4 content is higher in glycolytic and oxido-glycolytic muscles than in oxidative muscles. In conclusion, using both a functional test (insulin stimulation of glucose transport) and an immunological approach, this study demonstrates that ruminant muscles express GLUT4 protein. Our data also suggest that, in ruminants, glucose is the main energy-yielding substrate for glycolytic but not for oxidative muscles, and that insulin responsiveness may be lower in oxidative than in other skeletal muscles.


Molecules ◽  
2021 ◽  
Vol 26 (14) ◽  
pp. 4232
Author(s):  
Chien-Hui Wu ◽  
Chung-Hsiung Huang ◽  
Ming-Chuan Chung ◽  
Shun-Hsien Chang ◽  
Guo-Jane Tsai

Although the hypoglycemic potential of brewer’s yeast extract has been reported, there is limited information pertaining to the hypoglycemic ingredients of Saccharomyces pastorianus extract and their mechanisms of action available. This study aimed to investigate the in vivo and in vitro hypoglycemic effect of S. pastorianus extract and to elucidate its molecular mechanisms. S. pastorianus extract was mainly composed of proteins followed by carbohydrates. In diabetic rats, oral administration of S. pastorianus extract significantly reduced the levels of plasma glucose and enhanced the activity of hepatic glucose-6-phosphatase dehydrogenase. Treatment with S. pastorianus extract increased the localization of type 4 glucose transporter (GLUT4), PTP, and insulin receptor at 3T3-L1 cell membranes and raised the levels of P38 MAPK, PI3K, and AKT in the cytosol. In agreement with these results, pretreatment of 3T3-L1 cells with inhibitors of PTP, PI3K, Akt/PKB, and p38 MAPK inhibited glucose uptake induced by application of S. pastorianus extract. Most importantly, a 54 kDa protein with hypoglycemic activity was identified and suggested as the major ingredient contributing to the hypoglycemic activity of S. pastorianus extract. In summary, these results clearly confirm the hypoglycemic activity of S. pastorianus extract and provide critical insights into the underlying molecular mechanisms.


2015 ◽  
Vol 34 (9) ◽  
pp. 884-893 ◽  
Author(s):  
V Ramachandran ◽  
R Saravanan

In this study, we examined the in vivo effect and the mechanism of asiatic acid (AA) on glucose uptake in an insulin target skeletal muscle. Diabetic rats showed significantly increased levels of plasma glucose, thiobarbituric acid reactive substances, and lipid hydroperoxides, decreased levels of insulin and antioxidants, and impairment in insulin-signaling proteins such as insulin receptor (IR), insulin receptor substrate (IRS)-1/2, phosphoinositide 3-kinase (PI3K), Akt, and glucose transporter 4 (GLUT4) proteins. Oral treatment with AA (20 mg/kg body weight) showed near-normalized levels of plasma glucose, lipid peroxidation products, and antioxidants and improved insulin, IR, IRS-1/2, PI3K, Akt, and GLUT4 proteins. These findings suggest that AA improves glucose response by increasing GLUT4 in skeletal muscle through Akt and antioxidant defense in plasma and it also improves glucose homeostasis.


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