Postreceptor defect in insulin action in streptozotocin-induced diabetic rats

1989 ◽  
Vol 256 (5) ◽  
pp. E624-E630 ◽  
Author(s):  
H. Nishimura ◽  
H. Kuzuya ◽  
M. Okamoto ◽  
K. Yamada ◽  
A. Kosaki ◽  
...  
Keyword(s):  
Glucose Transporter ◽  
Insulin Dose ◽  
Insulin Binding ◽  
Diabetic Rats ◽  
Glucose Disposal ◽  
Maximal Response ◽  
Metabolic Clearance ◽  
Glucose Clamp Technique

To clarify the mechanism(s) responsible for the insulin resistance in streptozotocin (STZ)-treated diabetic rats, we studied insulin-induced glucose disposal by using the glucose clamp technique and measured insulin receptor and glucose transporter of muscles. The insulin dose-response curve of the metabolic clearance rate (MCR) of glucose revealed a decrease of the maximal response without a rightward shift in STZ rats. Maximal MCR was even lower when clamped at 300 rather than 150 mg/dl of blood glucose levels. Insulin binding to the crude plasma membrane of muscles from STZ rats was increased compared with controls. The number of glucose transporter of the plasma and microsomal membranes were significantly decreased in STZ rats. These in vivo and in vitro studies using skeletal muscles suggest that in STZ-treated diabetic rats 1) a defect or defects exist in the signal transduction mechanism of insulin in postbinding steps, 2) the decreased maximal MCR is related at least partly to the decrease of glucose transporter numbers, and 3) a defect in glucose metabolism (postglucose transport defect) is also present.

RES hyperphagocytosis by rats with streptozotocin-induced diabetes mellitus

1981 ◽  
Vol 240 (3) ◽  
pp. G225-G231
Author(s):  
R. P. Cornell
Keyword(s):  
Body Weight ◽  
Insulin Dose ◽  
Reticuloendothelial System ◽  
Diabetic Rats ◽  
Phagocytic Index ◽  
Control Value ◽  
Colloidal Carbon ◽  
Significant Difference

In contrast to previous studies of neutrophils from diabetic animals and humans in vitro and of macrophages from diabetic humans in vivo, which reported phagocytic depression, reticuloendothelial system (RES) hyperphagocytosis of colloidal carbon was observed in rats at 14 and 28 days after diabetes induction with streptozotocin (STZ). Carbon clearance half times were significantly enhanced to 6.3 +/- 0.79 and 8.1 +/- 1.04 min at 14 and 28 days post-STZ, respectively, compared with the nondiabetic value (12.7 +/- 0.98 min). The severity of uncontrolled STZ-induced diabetes in rats was confirmed by significant hypoinsulinemia, hyperglucagonemia, hyperglycemia, and hyperlipidemia. Although body weights of STZ-diabetic animals declined progressively, liver weights as a percent of body weight increased above the control value at 14 and 28 days post-STZ. In fact, expression of carbon phagocytosis as the corrected phagocytic index, which accounts for changes in liver and spleen weights relative to body weight, eliminated the significant difference between STZ-diabetic and nondiabetic animals. Antibiotic treatment of diabetic rats failed to alter the hyperphagocytosis, implying that a chronic bacterial infection was not the cause of phagocytic stimulation. Daily insulin replacements, but not a single large insulin dose to 14-day post-STZ rats, reversed the enhanced phagocytosis of colloidal carbon.

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.

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.

Insulin binding and glucose transport activity in cardiomyocytes of a diabetic rat

1986 ◽  
Vol 250 (4) ◽  
pp. E402-E406 ◽  
Author(s):  
E. C. Almira ◽  
A. R. Garcia ◽  
B. R. Boshell
Keyword(s):  
Glucose Transport ◽  
Insulin Binding ◽  
Diabetic Rats ◽  
Diabetic Rat ◽  
Heart Cells ◽  
Apparent Difference ◽  
Insulin Effect ◽  
Streptozotocin Induced Diabetes

We studied insulin binding and glucose transport in isolated adult cardiomyocytes from rats with 2-wk streptozotocin-induced diabetes. At 37 degrees C, cells from diabetic rats bound less 125I-insulin and exhibited lower rates of 3-O-methylglucose transport than cells from control rats. In contrast, the amount of 125I-insulin bound to myocytes at 4 degrees C was the same in both groups. Preincubation of cells from both groups with 10-10,000 ng/ml insulin significantly increased their basal rates of glucose transport by approximately 40%. However, the augmented rates in diabetics were still approximately 36% lower than the corresponding insulin-stimulated rates in the controls. When the glucose transport data were expressed as percent maximal insulin effect and plotted as a function of the amount of insulin bound, the curves obtained from both diabetic and nondiabetic controls were superimposable. These data demonstrate that 1) heart cells from diabetic rats bind less insulin than from control rats under conditions in which they exhibit impaired glucose transport rates, 2) there is no apparent difference in total receptor number between the two groups, but internalization of intact insulin appears to be diminished in diabetes, 3) coupling exists between insulin binding and glucose transport in both groups, and 4) these impaired processes are completely reversed by insulin treatment in vivo but not in vitro.

scholarly journals Exploration of Hypoglycemic Activity of Saccharomyces pastorianus Extract and Evaluation of the Molecular Mechanisms

Molecules ◽  
2021 ◽  
Vol 26 (14) ◽  
pp. 4232
Author(s):  
Chien-Hui Wu ◽  
Chung-Hsiung Huang ◽  
Ming-Chuan Chung ◽  
Shun-Hsien Chang ◽  
Guo-Jane Tsai
Keyword(s):  
P38 Mapk ◽  
Molecular Mechanisms ◽  
Glucose Transporter ◽  
Diabetic Rats ◽  
Hypoglycemic Activity ◽  
Limited Information ◽  
Saccharomyces Pastorianus ◽  
Glucose Transporter Glut4

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.

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

scholarly journals A Review on the Medicinal and Pharmacological Properties of Traditional Ethnomedicinal Plant Sonapatha, Oroxylum indicum

Sinusitis ◽  
2021 ◽  
Vol 5 (1) ◽  
pp. 71-89
Author(s):  
Ganesh Chandra Jagetia
Keyword(s):  
Glucose Transporter ◽  
Skin Diseases ◽  
Regulatory Element ◽  
Experimental Studies ◽  
Fatty Acid Synthetase ◽  
Preclinical Models ◽  
Oroxylin A ◽  
Oroxylum Indicum

Oroxylum indicum, Sonapatha is traditionally used to treat asthma, biliousness, bronchitis, diarrhea, dysentery, fevers, vomiting, inflammation, leukoderma, skin diseases, rheumatoid arthritis, wound injury, and deworm intestine. This review has been written by collecting the relevant information from published material on various ethnomedicinal and pharmacological aspects of Sonapatha by making an internet, PubMed, SciFinder, Science direct, and Google Scholar search. Various experimental studies have shown that Sonapatha scavenges different free radicals and possesses alkaloids, flavonoids, cardio glycosides, tannins, sterols, phenols, saponins, and other phytochemicals. Numerous active principles including oroxylin A, chrysin, scutellarin, baicalein, and many more have been isolated from the different parts of Sonapatha. Sonapatha acts against microbial infection, cancer, hepatic, gastrointestinal, cardiac, and diabetic disorders. It is useful in the treatment of obesity and wound healing in in vitro and in vivo preclinical models. Sonapatha elevates glutathione, glutathione-s-transferase, glutathione peroxidase, catalase, and superoxide dismutase levels and reduces aspartate transaminase alanine aminotransaminase, alkaline phosphatase, lactate dehydrogenase, and lipid peroxidation levels in various tissues. Sonapatha activates the expression of p53, pRb, Fas, FasL, IL-12, and caspases and inhibited nuclear factor kappa (NF-κB), cyclooxygenase (COX-2), tumor necrosis factor (TNFα), interleukin (IL6), P38 activated mitogen-activated protein kinases (MAPK), fatty acid synthetase (FAS), sterol regulatory element-binding proteins 1c (SREBP-1c), proliferator-activated receptor γ2 (PPARγ2), glucose transporter (GLUT4), leptin, and HPV18 oncoproteins E6 and E7 at the molecular level, which may be responsible for its medicinal properties. The phytoconstituents of Sonapatha including oroxylin A, chrysin, and baicalein inhibit the replication of SARS-CoV-2 (COVID-19) in in vitro and in vivo experimental models, indicating its potential to contain COVID-19 infection in humans. The experimental studies in various preclinical models validate the use of Sonapatha in ethnomedicine and Ayurveda.

scholarly journals Glucose Transporter 8 (GLUT8) Regulates Enterocyte Fructose Transport and Global Mammalian Fructose Utilization

Endocrinology ◽  
2012 ◽  
Vol 153 (9) ◽  
pp. 4181-4191 ◽  
Author(s):  
Brian J. DeBosch ◽  
Maggie Chi ◽  
Kelle H. Moley
Keyword(s):  
Glucose Transporter ◽  
Serum Insulin ◽  
Density Lipoprotein ◽  
Wild Type ◽  
In Vivo Models ◽  
The Metabolic Syndrome ◽  
High Fructose

Enterocyte fructose absorption is a tightly regulated process that precedes the deleterious effects of excess dietary fructose in mammals. Glucose transporter (GLUT)8 is a glucose/fructose transporter previously shown to be expressed in murine intestine. The in vivo function of GLUT8, however, remains unclear. Here, we demonstrate enhanced fructose-induced fructose transport in both in vitro and in vivo models of enterocyte GLUT8 deficiency. Fructose exposure stimulated [14C]-fructose uptake and decreased GLUT8 protein abundance in Caco2 colonocytes, whereas direct short hairpin RNA-mediated GLUT8 knockdown also stimulated fructose uptake. To assess GLUT8 function in vivo, we generated GLUT8-deficient (GLUT8KO) mice. GLUT8KO mice exhibited significantly greater jejunal fructose uptake at baseline and after high-fructose diet (HFrD) feeding vs. wild-type mice. Strikingly, long-term HFrD feeding in GLUT8KO mice exacerbated fructose-induced increases in blood pressure, serum insulin, low-density lipoprotein and total cholesterol vs. wild-type controls. Enhanced fructose uptake paralleled with increased abundance of the fructose and glucose transporter, GLUT12, in HFrD-fed GLUT8KO mouse enterocytes and in Caco2 cultures exposed to high-fructose medium. We conclude that GLUT8 regulates enterocyte fructose transport by regulating GLUT12, and that disrupted GLUT8 function has deleterious long-term metabolic sequelae. GLUT8 may thus represent a modifiable target in the prevention and treatment of malnutrition or the metabolic syndrome.

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.

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