Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In this study, the in vivo effects of insulin and chronic treatment with bis(maltolato)oxovanadium (IV) (BMOV) on protein kinase B (PKB) activity were examined in the liver and skeletal muscle from two animal models of diabetes, the STZ-diabetic Wistar rat and the fatty Zucker rat. Animals were treated with BMOV in the drinking water (0.75-1 mg/ml) for 3 (or 8) weeks and sacrificed with or without insulin injection. Insulin (5 U/kg, i.v.) increased PKBalpha activity more than 10-fold and PKBbeta activity more than 3-fold in both animal models. Despite the development of insulin resistance, insulin-induced activation of PKBalpha was not impaired in the STZ-diabetic rats up to 9 weeks of diabetes, excluding a role for PKBalpha in the development of insulin resistance in type 1 diabetes. Insulin-induced PKBalpha activity was markedly reduced in the skeletal muscle of fatty Zucker rats as compared to lean littermates (fatty: 7-fold vs. lean: 14-fold). In contrast, a significant increase in insulin-stimulated PKBalpha activity was observed in the liver of fatty Zucker rats (fatty: 15.7-fold vs. lean: 7.6-fold). Chronic treatment with BMOV normalized plasma glucose levels in STZ-diabetic rats and decreased plasma insulin levels in fatty Zucker rats but did not have any effect on basal or insulin-induced PKBalpha and PKBbeta activities. In conclusion (i) in STZ-diabetic rats PKB activity was normal up to 9 weeks of diabetes; (ii) in fatty Zucker rats insulin-induced activation of PKBalpha (but not PKBbeta) was markedly altered in both tissues; (iii) changes in PKBalpha activity were tissue specific; (iv) the glucoregulatory effects of BMOV were independent of PKB activity.
Mol Cell Biochem 2001 Jul
PMID:In vivo effects of insulin and bis(maltolato)oxovanadium (IV) on PKB activity in the skeletal muscle and liver of diabetic rats. 1168 16

The heart, like other organs, possesses an internal circadian clock. These clocks provide the selective advantage of anticipation, enabling the organ to prepare for a given stimulus, thereby optimizing the appropriate response. The heart in diabetes is associated with alterations in morphology, gene expression, metabolism and contractile performance. The present study investigated whether diabetes also alters the circadian clock in the heart. Insulin-dependent diabetes mellitus was induced in rats by treatment with streptozotocin (STZ; 65 mg/kg). STZ increased humoral (glucose and non-esterified fatty acids) and heart gene expression (myosin heavy chain beta, pyruvate dehydrogenase kinase 4 and uncoupling protein 3) markers of diabetes. The circadian patterns of gene expression of seven components of the mammalian clock (bmal1, clock, cry1, cry2, per1, per2 and per3), as well as three clock output genes (dbp, hlf and tef), were compared in hearts isolated from control and STZ-induced diabetic rats. All components of the clock investigated possessed circadian rhythms of gene expression. In the hearts isolated from STZ-induced diabetic rats, the phases of these circadian rhythms were altered (approximately 3 h early) compared to those observed for control hearts. The clock in the heart has therefore lost normal synchronization with its environment during diabetes. Whether this loss of synchronization plays a role in the development of contractile dysfunction of the heart in diabetes remains to be determined.
J Mol Cell Cardiol 2002 Feb
PMID:Alterations of the circadian clock in the heart by streptozotocin-induced diabetes. 1185 61

This study aims at exploring specific aspects of D-glucose metabolism, so far not yet investigated, in pancreatic islets from adult control rats and animals (STZ rats) injected with streptozotocin during the neonatal period. The latter animals, which represent a current model of type-2 diabetes, displayed a lower body weight, higher plasma D-glucose concentration and lower insulinogenic index than control rats. The protein, DNA and insulin content were all also lower in islets prepared from STZ, rather than control rats. In the presence of 10.0 mM D-glucose, the paired ratio between D-[U-14C]glucose oxidation and D-[5-3H]glucose utilization was also decreased in the islets from STZ rats. No significant difference between control and STZ rats was observed, however, in terms of the ratios between D-[3-3H]glucose and D-[5-3H]glucose utilization, between the generation of radioactive lactate from 14C-labelled D-glucose and tritiated D-glucose utilization and between D-[1-14C]glucose and D-[6-14C]glucose oxidation. These findings reinforce the view that the previously documented preferential impairment of the oxidative modality of glycolysis in islets from STZ rats contrasts with the absence of any major anomaly in other variables of D-glucose catabolism.
Int J Mol Med 2002 Apr
PMID:Metabolism of D-[3-3H]glucose, D-[5-3H]glucose, D-[U-14C]glucose, D-[1-14C]glucose and D-[6-14C]glucose in pancreatic islets in an animal model of type-2 diabetes. 1189 32

3,7-dimethyl-1-(5-oxohexyl) xanthine, pentoxifylline (PTX) is shown to affect cytokine-induced apoptosis in several experimental models and clinical conditions. It had been also shown to prevent insulitis and hyperglycemia in non-obese diabetic (NOD) mice, and mice and rats susceptible to diabetes induction with multiple low-doses of streptozotocin (MLD-STZ). We therefore analysed the development of diabetes and apoptosis of pancreatic beta islet cells in CBA/mice after diabetes induction with MLD-STZ. We have evaluated the effect of PTX on the level of apoptosis in the islet at different time intervals after diabetes induction. Complementary histological and immunohistochemical studies and analyses of the expression of cytokines and nitric oxide have also been done. It was concluded that PTX significantly attenuated apoptosis of the beta-cells in the islet and suppressed the induction of diabetes. Our data are compatible with the notion that interferon-gamma (IFN-gamma)/tumor necrosis factor (TNF)/nitric oxide (NO)-induced apoptosis of beta-cells in experimental diabetes is attenuated by PTX.
Mol Immunol 2002 May
PMID:Downregulation of apoptosis in the target tissue prevents low-dose streptozotocin-induced autoimmune diabetes. 1200 72

Etomoxir, an inhibitor of mitochondrial carnitine palmitoyltransferase-1, is known to attenuate the changes in myosin isoforms and sarcoplasmic reticular function that occur in diabetic rat hearts. In the present study, we tested the hypothesis that etomoxir also prevents the diabetes-induced depression of sarcolemmal (SL) Na+-K+ATPase activity by differentially affecting its alpha and beta-subunit levels. Streptozotocin-induced diabetes was associated with a decreased in alpha2-, alpha3-subunit levels, whereas the alpha1-and beta1-subunits were unchanged. Treatment of diabetic rats for 4 weeks with etomoxir (8 mg/kg/day) increased the alpha1-subunit levels, but failed to prevent the decrease in alpha2- and alpha3-subunit levels. In euglycemic control rats, etomoxir increased the alpha1-subunit protein level per g heart weight, but did not alter the alpha2-, alpha3- and beta1-subunit levels. The large decrease in Na+-K+ ATPase activity per g heart weight in diabetic rats was prevented by etomoxir, which suggests that the increased alpha1-subunit levels seen with this drug compensated for the decreased alpha2- and alpha3-subunit levels. The SL yield was also increased by etomoxir in euglycemic rats in proportion to the higher alpha1-subunit level, which resulted in an unchanged alpha1-content when expressed per mg SL protein; however, the alpha2- and beta1-subunit levels were reduced (p < 0.05). The depressed alpha2- and beta3 subunit levels of diabetic rats were associated with reduced mRNA abundance. However, no increase in alpha1-subunit mRNA abundance was seen in the etomoxir treated rats, which suggests that possibly post-transcriptional mechanisms are occurring in these hearts.
Mol Cell Biochem 2002 Mar
PMID:Differential effects of etomoxir treatment on cardiac Na+-K+ ATPase subunits in diabetic rats. 1203 Mar 80

The activity of adenosine kinase is significantly impaired in tissues of diabetic rat. Changes in the activity of adenosine kinase were accompanied by alterations in its mRNA and protein level. These changes depended on insulin level and were not related to glucose level. During the first 7 h after insulin treatment the level of adenosine kinase mRNA, protein and enzymatic activity in kidneys, liver and heart returned to normal values. The observed relation between insulin and adenosine kinase expression level may suggest that insulin increases the rate of adenosine kinase gene transcription. Decreased activity of adenosine kinase was associated with elevated level of adenosine in diabetic tissues. On the 10th day after the STZ treatment there was a 3.5 and 2-fold increase in adenosine content in heart and liver, respectively. On the other hand, in diabetic kidney adenosine level was elevated only by 20%. Administration of insulin to diabetic rats resulted in a drop of adenosine to the level seen in normal heart and liver whereas, in kidneys the adenosine content was 50% lower than that observed under normal conditions. The time-dependent coarse of changes in adenosine level was different from that observed for adenosine kinase activity, what may suggest that other factors, possibly nucleoside transporters are also important for controlling adenosine level in the cell.
Mol Cell Biochem 2002 Jul
PMID:Insulin restores expression of adenosine kinase in streptozotocin-induced diabetes mellitus rats. 1219 Jan 16

Plants in the form of food or other remedial forms have been used for the treatment of various human ailments. Diabetes is one such disorder in which various form of plants and herbal remedies have been tried. Brassicajuncea (BJ) seeds (Rai) are consumed in India as a spice in various food items. Previous studies have shown the hypoglycemic effect of this plant in rats. The present study was undertaken to study the hypoglycemic and antihyperglycemic of various strengths (5, 10 and 15%) of BJ seed diet in alloxan and streptozotocin induced diabetes in albino rats. In addition, key enzymes of carbohydrate metabolism (glucokinase--EC 2.7.1.1, hexokinase--EC 2.7.1.1, and phosphofructokinase--EC 2.7.1.11) and hepatic glycogen content was also assessed to understand the mechanism of action. BJ diet (10 and 15%) showed significant antihyperglycemic effect in alloxan (35 mg/kg) but not in STZ (60 mg/kg) rats. It also failed to modulate the hepatic glycogen content and enzyme activities.
Mol Cell Biochem 2002 Dec
PMID:Hypoglycemic and antihyperglycemic effect of Brassicajuncea diet and their effect on hepatic glycogen content and the key enzymes of carbohydrate metabolism. 1248 30

Transcription factors of the FoxO family in mammals are orthologues of the Caenorhabditis elegans forkhead factor DAF-16, which has been characterized as a target of insulin-like signalling. Three members of this family have been identified in rodents: FoxO1, FoxO3 and FoxO4, originally termed FKHR, FKHRL1 and AFX respectively. A number of in vitro studies have revealed that FoxOs are regulated through phosphorylation in response to insulin and related growth factors, resulting in their nuclear exclusion and inactivation. To clarify the mechanisms involved in the regulation of these factors in vivo, we investigated in the present study whether or not, and if so how, their mRNA levels in rat liver respond to the stimuli of several nutritional and hormonal factors. Imposed fasting for 48 h significantly elevated mRNA levels of FoxO1 (1.5-fold), FoxO3 (1.4-fold), and FoxO4 (1.6-fold). Refeeding for 3 h recovered the induced mRNA levels of FoxO1 and FoxO3 to the control levels, but did not affect that of FoxO4. FoxO1 and FoxO4 mRNA levels were proved to be highly reflective of their protein levels measured by Western immunoblotting. Of the three FoxO genes, FoxO4 only showed altered levels of mRNA (a 1.5-fold increase) in response to a protein-free diet. Streptozotocin-induced diabetes for 28 days decreased hepatic mRNA levels of FoxO1 and FoxO3 and increased the level of FoxO4 mRNA, but short-term (7 days) diabetes had fewer effects on the expression of these genes. Insulin replacement partially restored the FoxO1 and FoxO4 mRNA levels, but had no effect on the FoxO3 mRNA level. Daily administration for 1 week of dexamethasone, a synthetic glucocorticoid, increased the mRNA levels of FoxO1 (1.8-fold) and FoxO3 (2.4-fold). These results show that the FoxO genes respond differently to nutritional and hormonal factors, suggesting a new mechanism for the regulation of FoxO-dependent gene expression by these factors. Moreover, changes of FoxO1 and FoxO4 in the nucleus in response to fasting also suggest that the regulation of nucleus/cytoplasm translocation actually functions in vivo.
J Mol Endocrinol 2003 Apr
PMID:Nutritional and hormonal factors control the gene expression of FoxOs, the mammalian homologues of DAF-16. 1268 47

In the present study, oxidative stress in diabetic model and the effect of garlic oil or melatonin treatment were examined. Streptozotocin (60 mg/kg body weight, i.p.)-induced diabetic rats, showed a significant increase of plasma glucose, total lipids, triglyceride, cholesterol, lipid peroxides, nitric oxide and uric acid. Concomitantly, significant decreases in the levels of antioxidants ceruloplasmin, albumin and total thiols were found in the plasma of diabetic rats. Lipid peroxide levels were significantly increased in erythrocyte lysate and in homogenates of liver and kidney, while superoxide dismutase (SOD) activities were decreased in tissue homogenates of liver and kidney. Treatment of diabetic rats with garlic oil (10 mg/kg i.p.) or melatonin (200 microg/kg i.p.) for 15 days significantly increased plasma levels of total thiol, ceruloplasmin activities, albumin. Lipid peroxides, uric acid, blood glucose, total lipid, triglyceride and cholesterol were decreased significantly after treatment with garlic oil or melatonin. Nitric oxide levels were decreased significantly in rats treated with melatonin only. In erythrocytes lysate, glutathione S-transferase (GST) activities were increased significantly in rats treated with garlic oil or melatonin, while lipid peroxides decreased significantly and total thiol increased significantly in melatonin or garlic oil treatment, respectively. In liver homogenates of rats treated with garlic or melatonin, lipid peroxides were decreased significantly, and GST activities increased significantly, while SOD activities were increased significantly in liver and kidney after garlic or melatonin treatment. The results suggest that garlic oil or melatonin may effectively normalize the impaired antioxidants status in streptozotocin induced-diabetes. The effects of these antioxidants of both agents may be useful in delaying the complicated effects of diabetes as retinopathy, nephropathy and neuropathy due to imbalance between free radicals and antioxidant systems. Moreover, melatonin may be more powerful free radical scavenger than garlic oil.
Comp Biochem Physiol A Mol Integr Physiol 2003 Aug
PMID:Oxidative stress in streptozotocin-induced diabetic rats: effects of garlic oil and melatonin. 1289 May 44

Several studies have been carried out to evaluate the alterations in mitochondrial functions of diabetic rats. However, some of the results reported are controversial, since experimental conditions, such as aging, and/or strain of animals used were different. The purpose of this study was to evaluate the metabolic changes in liver mitochondria, both in the presence of severe hyperglycaemia (STZ-treated rats) and mild hyperglycaemia (Goto-Kakizaki (GK) rats). Moreover, metabolic alterations were evaluated both at initial and at advanced states of the disease. We observed that both models of type 1 and type 2 diabetes presented alterations on respiratory chain activity. Because of continual severe hyperglycaemia, 9 weeks after the induction of diabetes, the respiratory function declined in STZ-treated rats, as observed by membrane potential and respiratory ratios (RCR, P/O, and FCCP-stimulated respiration) assessment. In contrast, GK rats of 6 months age presented increased respiratory ratios. To localize which respiratory complexes are affected by diabetes, enzymatic respiratory chain activities were evaluated. We observed that succinate dehydrogenase and cytochrome c oxidase activities were significantly augmented both in STZ-treated rats and GK rats of 6 months age. Moreover, H(+)-ATPase activity was also significantly increased in STZ-treated rats with 3 weeks of diabetes and in GK rats of 6 months age as compared to controls. Therefore, these results clearly suggest that both animal models of diabetes present some metabolic adjustments in order to circumvent the deleterious effects promoted by the high glucose levels typical of the disease.
J Biochem Mol Toxicol 2003
PMID:Diabetes and mitochondrial bioenergetics: alterations with age. 1289 45


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>