Lowering of plasma glucose in diabetic rats by antilipolytic agents

1988 ◽  
Vol 254 (1) ◽  
pp. E23-E30 ◽  
Author(s):  
G. M. Reaven ◽  
H. Chang ◽  
H. Ho ◽  
C. Y. Jeng ◽  
B. B. Hoffman
Keyword(s):  
Glucose Uptake ◽  
Plasma Glucose ◽  
Plasma Free Fatty Acid ◽  
Diabetic Rats ◽  
Plasma Insulin Concentration ◽  
Glucose Response ◽  
Adenosine Receptor Agonist ◽  
Lower Plasma Glucose

Both nicotinic acid (NA) and the adenosine receptor agonist phenylisopropyladenosine (PIA) are potent antilipolytic agents. We have evaluated the ability of these compounds to lower plasma glucose concentration in 450-g male diabetic rats. Diabetes was induced by intravenous streptozotocin, and the rats were studied 7-10 days later. Mean (+/- SE) fasting glucose decreased 4 h after subcutaneous injections of PIA at 0 and 2 h. A similar change in plasma glucose level was also seen in rats injected with NA. The decrease in the concentration of plasma glucose in both instances was preceded by marked sustained reductions in plasma free fatty acid (FFA) concentrations; FFA decreased in PIA-injected rats and in response to NA. With injection of normal saline, neither plasma glucose nor FFA concentrations decreased in diabetic rats. There was no change in the plasma insulin concentration of rats that had hypoglycemic responses to PIA or NA. In vitro glucose uptake was determined in isolated adipocytes, and both PIA and NA were shown to increase basal and maximal insulin-stimulated glucose uptake. The stimulating effect of the two compounds was similar, and the magnitude of the effect was comparable in adipocytes from either normal or diabetic rats. As a result, neither NA nor PIA could restore the defects in glucose transport to normal in adipocytes from diabetic rats. Insulin-stimulated glucose uptake was assessed in vivo by determining the steady-state glucose response of diabetic rats to a continuous infusion of insulin and glucose and was found to be significantly enhanced in response to NA compared with NaCl.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Effects of dichloroacetate on the metabolism of glucose, pyruvate, acetate, 3-hydroxybutyrate and palmitate in rat diaphragm and heart muscle in vitro and on extraction of glucose, lactate, pyruvate and free fatty acids by dog heart in vivo

1973 ◽  
Vol 134 (4) ◽  
pp. 1067-1081 ◽  
Author(s):  
Anthony McAllister ◽  
S. P. Allison ◽  
Philip J. Randle
Keyword(s):  
Fatty Acids ◽  
Free Fatty Acids ◽  
Plasma Free Fatty Acid ◽  
Diabetic Rats ◽  
Inhibitory Effects ◽  
Acetyl Coa ◽  
Citrate Concentration ◽  
Lactate And Pyruvate

1. The extractions of glucose, lactate, pyruvate and free fatty acids by dog heart in vivo were calculated from measurements of their arterial and coronary sinus blood concentration. Elevation of plasma free fatty acid concentrations by infusion of intralipid and heparin resulted in increased extraction of free fatty acids and diminished extractions of glucose, lactate and pyruvate by the heart. It is suggested that metabolism of free fatty acids by the heart in vivo, as in vitro, may impair utilization of these substrates. These effects of elevated plasma free fatty acid concentrations on extractions by the heart in vivo were reversed by injection of dichloroacetate, which also improved extraction of lactate and pyruvate by the heart in vivo in alloxan diabetes. 2. Sodium dichloroacetate increased glucose oxidation and pyruvate oxidation in hearts from fed normal or alloxan-diabetic rats perfused with glucose and insulin. Dichloroacetate inhibited oxidation of acetate and 3-hydroxybutyrate and partially reversed inhibitory effects of these substrates on the oxidation of glucose. In rat diaphragm muscle dichloroacetate inhibited oxidation of acetate, 3-hydroxybutyrate and palmitate and increased glucose oxidation and pyruvate oxidation in diaphragms from alloxan-diabetic rats. Dichloroacetate increased the rate of glycolysis in hearts perfused with glucose, insulin and acetate and evidence is given that this results from a lowering of the citrate concentration within the cell, with a consequent activation of phosphofructokinase. 3. In hearts from normal rats perfused with glucose and insulin, dichloroacetate increased cell concentrations of acetyl-CoA, acetylcarnitine and glutamate and lowered those of aspartate and malate. In perfusions with glucose, insulin and acetate, dichloroacetate lowered the cell citrate concentration without lowering the acetyl-CoA or acetylcarnitine concentrations. Measurements of specific radioactivities of acetyl-CoA, acetylcarnitine and citrate in perfusions with [1-14C]acetate indicated that dichloroacetate lowered the specific radio-activity of these substrates in the perfused heart. Evidence is given that dichloroacetate may not be metabolized by the heart to dichloroacetyl-CoA or dichloroacetylcarnitine or citrate or CO2. 4. We suggest that dichloroacetate may activate pyruvate dehydrogenase, thus increasing the oxidation of pyruvate to acetyl-CoA and acetylcarnitine and the conversion of acetyl-CoA into glutamate, with consumption of aspartate and malate. Possible mechanisms for the changes in cell citrate concentration and for inhibitory effects of dichloroacetate on the oxidation of acetate, 3-hydroxybutyrate and palmitate are discussed.

scholarly journals Insulin-regulated aminopeptidase inhibitors do not alter glucose handling in normal and diabetic rats

2017 ◽  
Vol 58 (4) ◽  
pp. 193-198 ◽  
Author(s):  
Anthony L Albiston ◽  
Mauricio Cacador ◽  
Puspha Sinnayah ◽  
Peta Burns ◽  
Siew Yeen Chai
Keyword(s):  
Glucose Uptake ◽  
Glucose Transporter ◽  
Specific Inhibitor ◽  
Diabetic Rats ◽  
Whole Body ◽  
Aminopeptidase Activity ◽  
Oral Glucose ◽  
Glucose Challenge

Insulin-regulated aminopeptidase (IRAP) co-localizes with the glucose transporter 4 (GLUT4) in GLUT4 storage vesicles (GSV) in insulin-responsive cells. In response to insulin, IRAP is the only transmembrane enzyme known to translocate together with GLUT4 to the plasma membrane in adipocytes and muscle cells. Although the intracellular region of IRAP is associated with GLUT4 vesicle trafficking, the role of the aminopeptidase activity in insulin-responsive cells has not been elucidated. The aim of this study was to investigate whether the inhibition of the aminopeptidase activity of IRAP facilitates glucose uptake in insulin-responsive cells. In both in vitro and in vivo studies, inhibition of IRAP aminopeptidase activity with the specific inhibitor, HFI-419, did not modulate glucose uptake. IRAP inhibition in the L6GLUT4myc cell line did not alter glucose uptake in both basal and insulin-stimulated state. In keeping with these results, HFI419 did not affect peripheral, whole-body glucose handling after an oral glucose challenge, neither in normal rats nor in the streptozotocin (STZ)-induced experimental rat model of diabetes mellitus (DM). Therefore, acute inhibition of IRAP aminopeptidase activity does not affect glucose homeostasis.

scholarly journals Effect of Alpinia calcarata on glucose uptake in diabetic rats-an in vitro and in vivo model

2014 ◽  
Vol 13 (1) ◽  
Author(s):  
Ramya Rajasekar ◽  
Kalaiselvi Manokaran ◽  
Narmadha Rajasekaran ◽  
Gomathi Duraisamy ◽  
Devaki Kanakasabapathi
Keyword(s):  
Glucose Uptake ◽  
Diabetic Rats ◽  
In Vivo Model

In vivo and in vitro resistance to maximal insulin-stimulated glucose disposal in insulin deficiency

1985 ◽  
Vol 249 (3) ◽  
pp. E312-E316 ◽  
Author(s):  
E. Dall'Aglio ◽  
H. Chang ◽  
C. B. Hollenbeck ◽  
C. E. Mondon ◽  
C. Sims ◽  
...  
Keyword(s):  
Glucose Uptake ◽  
Glucose Transport ◽  
Diabetic Rats ◽  
Glucose Disposal ◽  
Diabetic Rat ◽  
Insulin Deficiency ◽  
Fat Cell ◽  
Total Body

The effect of streptozotocin-induced diabetes mellitus on maximal insulin-stimulated glucose uptake in the rat was studied in isolated adipocyte, perfused hindlimb, and the intact organism. Basal glucose transport per fat cell was reduced by approximately two-thirds (P less than 0.001), being associated with a similar decrease in glucose oxidation per fat cell (P less than 0.001). There was also a significant decrease (P less than 0.001) in basal glucose uptake by perfused hindlimb of diabetic rats of approximately 40%. Furthermore, maximal insulin-stimulated glucose transport and oxidation were approximately 50% lower (P less than 0.001) in fat cells of diabetic as compared with control rats. In contrast, maximal insulin-stimulated glucose disposal by perfused hindlimbs from diabetic and control rats was similar, and this was also true of the ability of insulin to maximally stimulate glucose uptake in the intact normal and diabetic rat. These findings indicate that variation exists in the manner in which insulin-sensitive tissues respond to experimentally induced insulin deficiency and support the view that total body glucose disposal is primarily related to insulin action on muscle.

scholarly journals Evaluation ofα-Glucosidase Inhibitory Effect of 50% Ethanolic Standardized Extract ofOrthosiphon stamineusBenth in Normal and Streptozotocin-Induced Diabetic Rats

2015 ◽  
Vol 2015 ◽  
pp. 1-6 ◽  
Author(s):  
Elsnoussi Ali Mohamed ◽  
Mariam Ahmad ◽  
Lee Fung Ang ◽  
Mohd. Zaini Asmawi ◽  
Mun Fei Yam
Keyword(s):  
Plasma Glucose ◽  
Inhibitory Activity ◽  
Ethanolic Extract ◽  
Inhibitory Effect ◽  
Diabetic Rats ◽  
Lower Plasma ◽  
Antidiabetic Effect ◽  
Glucose Levels ◽  
Lower Plasma Glucose

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.

Glucose uptake through translocation and activation of GLUT4 in PI3K/Akt signaling pathway by asiatic acid in diabetic rats

2015 ◽  
Vol 34 (9) ◽  
pp. 884-893 ◽  
Author(s):  
V Ramachandran ◽  
R Saravanan
Keyword(s):  
Skeletal Muscle ◽  
Insulin Receptor ◽  
Glucose Uptake ◽  
Plasma Glucose ◽  
Glucose Transporter ◽  
Oral Treatment ◽  
Diabetic Rats ◽  
Lipid Hydroperoxides ◽  
Asiatic Acid ◽  
Glucose Response

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.

scholarly journals Amelioration of lipid peroxidation in vivo and in vitro by Satureja khozestanica essential oil in alloxan-induced diabetic rats

2014 ◽  
Vol 13 (1) ◽  
Author(s):  
Hassan Ahmadvand ◽  
Majid Tavafi ◽  
Ali Khosrowbeygi ◽  
Gholamreza Shahsavari ◽  
Maryam Hormozi ◽  
...  
Keyword(s):  
Lipid Peroxidation ◽  
Essential Oil ◽  
Diabetic Rats

Sequoyitol ameliorates diabetic nephropathy in diabetic rats induced with a high-fat diet and a low dose of streptozotocin

2014 ◽  
Vol 92 (5) ◽  
pp. 405-417 ◽  
Author(s):  
Xian-Wei Li ◽  
Yan Liu ◽  
Wei Hao ◽  
Jie-Ren Yang
Keyword(s):  
Diabetic Nephropathy ◽  
Blood Glucose ◽  
High Fat Diet ◽  
Low Dose ◽  
Serum Insulin ◽  
Fasting Blood Glucose ◽  
Diabetic Rats ◽  
High Fat

Sequoyitol decreases blood glucose, improves glucose intolerance, and enhances insulin signaling in ob/ob mice. The aim of this study was to investigate the effects of sequoyitol on diabetic nephropathy in rats with type 2 diabetes mellitus and the mechanism of action. Diabetic rats, induced with a high-fat diet and a low dose of streptozotocin, and were administered sequoyitol (12.5, 25.0, and 50.0 mg·(kg body mass)−1·d−1) for 6 weeks. The levels of fasting blood glucose (FBG), serum insulin, blood urea nitrogen (BUN), and serum creatinine (SCr) were measured. The expression levels of p22phox, p47phox, NF-κB, and TGF-β1 were measured using immunohistochemisty, real-time PCR, and (or) Western blot. The total antioxidative capacity (T-AOC), as well as the levels of malondialdehyde (MDA) and reactive oxygen species (ROS) were also determined. The results showed that sequoyitol significantly decreased FBG, BUN, and SCr levels, and increased the insulin levels in diabetic rats. The level of T-AOC was significantly increased, while ROS and MDA levels and the expression of p22phox, p47phox, NF-κB, and TGF-β1 were decreased with sequoyitol treatment both in vivo and in vitro. These results suggested that sequoyitol ameliorates the progression of diabetic nephropathy in rats, as induced by a high-fat diet and a low dose of streptozotocin, through its glucose-lowering effects, antioxidant activity, and regulation of TGF-β1 expression.

Sign in / Sign up

Export Citation Format

Share Document