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

Sustained hyperglycemia allows the preferential labelling of pancreatic glycogen by D-[U-14C]glucose in control rats, as compared to animals previously injected with streptozotocin (STZ rats). The major aim of the present study was to investigate whether a sizeable difference between control and STZ rats could also be observed in terms of the radioactive content of the pancreatic gland 8 h after the intravenous injection of 2-deoxy-2-[18F]fluoro-D-glucose, both types of animals being examined at the same level of hyperglycemia. Although the radioactive content of muscle, liver and kidney was lower in STZ rats than in control animals, such a difference failed to achieve statistical significance in brain, hypophysis, pancreas and parotid gland. It is proposed, therefore, that 11C-labelled D-glucose, rather than 2-deoxy-2-[18F]fluoro-D-glucose should be used in the perspective of the non-invasive imaging of the endocrine pancreas.
Int J Mol Med 2000 Nov
PMID:Fate of 2-deoxy-2-[18F]fluoro-D-glucose in hyperglycemic rats. 1102 22

D-mannoheptulose was recently proposed as a tool to label preferentially insulin-producing cells in the pancreatic gland in the perspective of the non-invasive imaging of the endocrine pancreas. In such a perspective, we have now synthesized 1-deoxy-1-[125I]iodo-D-mannoheptulose ([125I]MH) and examined its uptake by different rat cell types. No phosphorylation of [125I]MH by bovine heart hexokinase could be detected. The apparent distribution space of [125I]MH largely exceeded that of [U-14C]sucrose, considered as an extracellular marker, in erythrocytes, parotid cells, hepatocytes, pancreatic pieces and isolated pancreatic islets. Relative to the mean intracellular distribution space of 3HOH, that of [125I]MH was not significantly different in pancreatic pieces from either normal rats or streptozotocin-induced diabetic animals (STZ rats). In pancreatic islets, the uptake of [125I]MH was decreased at low temperature, but failed to be significantly affected by cytochalasin B. Sixty min after the intravenous injection of [125I]MH, the radioactive content of selected organs displayed the following hierarchy: muscle<pancreas<liver<parotid<kidney<plasma. In this respect, there was no obvious difference between control and STZ rats. Taken as a whole, these findings suggest that 1-deoxy-1-[125I]iodo-D-mannoheptulose does not display the same specificity towards GLUT2, as that previously documented in the case of D-[3H]- mannoheptulose.
Int J Mol Med 2001 May
PMID:Uptake of 1-deoxy-1-[125I]iodo-D-mannoheptulose by different cell types: in vitro and in vivo experiments. 1129 10

As judged from morphological criteria, glycogen accumulates to a larger extent in insulin-producing B-cells than in acinar cells of the pancreas in situations of sustained hyperglycemia. In the present study, the glycogen content of the pancreatic gland and liver was measured in either euglycemic or glucose-infused hyperglycemic control rats, as well as in streptozotocin-induced diabetic rats. Whilst the glycogen content of the pancreas was significantly higher in STZ rats than in control euglycemic rats, it was further enhanced in glucose-infused control rats, despite the fact that the latter animals were not more severely hyperglycemic and for a shorter time than STZ rats. From these measurements, it was estimated that, relative to wet weight, the glycogen content was, under the present experimental conditions, about 75 times higher in insulin-producing than other pancreatic cells. Moreover, it is proposed that the intravenous administration of glucagon may help in distinguishing between the glycogen present in the endocrine and exocrine moieties of the pancreatic gland, this hormone being apparently unable to provoke glycogenolysis in the exocrine pancreas, at variance with the situation prevailing in isolated pancreatic islets.
Mol Cell Biochem 2001 Mar
PMID:Pancreatic and hepatic glycogen content in normoglycemic and hyperglycemic rats. 1135 52

We have previously shown that infection with Plasmodium yoelii malaria or injection of extracts from malaria-parasitized red cells induces hypoglycemia in normal mice and normalizes the hyperglycemia in mice made moderately diabetic with streptozotocin. Inositol phosphoglycans (IPGs) are released outside cells by hydrolysis of membrane-bound glycosylphosphatidylinositols (GPIs), and act as second messengers mediating insulin action. The C57BL/Ks-db/db and C57BL/6J-ob/ob mice offer good models for studies on human obesity and Type 2 diabetes. In the present study, we show that a single iv injection of IPG-A or IPG-P extracted from P. yoelii significantly (P < 0.02) lowers the blood glucose in STZ-diabetic, db/db, and in ob/ob mice for at least 4--6 h. Using rat white adipocytes, IPG-P increased lipogenesis by 20--30% in the presence and absence of maximal concentrations of insulin (10(-8) M) (P < 0.01) and stimulated pyruvate dehydrogenase (PDH) phosphatase in a dose-related manner. Both IPG-A and IPG-P inhibited c-AMP-dependent protein kinase (PKA) in a dose-related manner. Compositional analysis of IPGs after 24 h hydrolysis revealed the presence of myo-inositol, phosphorus, galactosamine, glucosamine, and glucose in both IPG-A and IPG-P. However, hydrolysis of IPGs for 4 h highlighted differences between IPG-A and IPG-P. There are some functional similarities between P. yoelii IPGs and those previously described for mammalian liver. However, this is the first report of the hypoglycemic effect of IPGs in murine models of Type 2 diabetes. We suggest that IPGs isolated from P. yoelii, when fully characterized, may provide structural information for the synthesis of new drugs for the management of diabetes mellitus.
Mol Genet Metab 2001 Jul
PMID:Reversal of type 2 diabetes in mice by products of malaria parasites. II. Role of inositol phosphoglycans (IPGs). 1146 Nov 92

A reduced ability to regenerate peripheral axons may be partly responsible for diabetic neuropathy. The source of the impairment has not been narrowed down to axonal or Schwann cell failure. We used nerve grafts from control or diabetic donor rats transplanted into control or diabetic hosts to pursue this differential diagnosis. An isograft between the left sciatic nerves of inbred Lewis rats was performed 8 weeks after STZ treatment and on age-matched controls. The nerve exchanges were control-control, control-diabetic, diabetic-control and diabetic-diabetic. At postsurgical day 14, nerves were excised and analysed for levels of axonal markers, total and phosphorylated neurofilament, and Schwann cell receptors, ErbB2 and p75(NTR), using immunohistochemistry and Western blotting. The aim was to measure ingress of axonal markers into the graft and judge the appropriateness of Schwann cell phenotype changes. Transfer of nerve from diabetic to control rats resulted in a doubling in neurofilament, both phosphorylated and nonphosphorylated (both P<0.05). ErbB2 was decreased in grafts from diabetic rats (53% of control, P<0.05) and p75(NTR) levels were increased in both types of graft in diabetic rats (to 300-400% of controls, P<0.05). Schwann cells in diabetic nerve grafts showed receptor levels more similar to controls when placed into a normal environment and the converse also appeared to hold. TUNEL staining revealed increased apoptosis in diabetic nerve distal to the graft. The data show that alterations in Schwann cell phenotype in diabetes are reversed by transfer to control rats and develop in normal nerve after transfer to a diabetic host.
Brain Res Mol Brain Res 2001 Aug 15
PMID:Effects of experimental diabetes on axonal and Schwann cell changes in sciatic nerve isografts. 1148 49

The changes in beta-adrenergic receptors and in adenylate cyclase (AC) activity were investigated in parotid glands from rats with acute diabetic mellitus (DM) induced by a single injection of streptozotocin (STZ, 80 mg/kg). The animals were divided into three groups: control rats, DM rats, and insulin-treated DM rats. Experiments were performed 7 days after the injection of STZ. Amylase and norepinephrine (NE) contents in parotid glands were markedly decreased in DM rats in comparison with control rats. The density of beta-adrenergic receptor decreased in DM rats, but its affinity for ligand was unaffected. The effect of GTP on isoprenaline (ISO)-stimulated adenylate cyclase (AC) activity significantly decreased in DM rats, but forskolin-stimulated AC activity was unaltered. In addition, diabetes induced the blunted response of AC activity to ISO. The changes in AC activity and in amylase content induced by diabetes were restored by insulin, but those in NE content and receptor density could not. These observations indicate that diabetes decreases NE and amylase contents, receptor density, and receptor-AC coupling in parotid gland, and that these changes would occur in the earlier stage of acute STZ-induced diabetic state.
Res Commun Mol Pathol Pharmacol 2000
PMID:Beta-adrenergic receptors and adenylate cyclase activity in the parotid acinar cells from acute streptozotocin-induced diabetic rats. 1148 85

The possible promoting effect of streptozotocin (STZ; 65 mg/kg body weight, intraperitoneal)-induced diabetes during 2-acetylaminofluorene (2-AAF; 0.04% in basal diet)-initiated hepatocarcinogenesis and modulatory effect of 1alpha,25-dihydroxyvitamin D3 (VD3; 0.3 microg/0.1 ml in propylene glycol, per os) were investigated by monitoring chromosomal aberrations (CAs), DNA strand breaks and specific DNA adducts in rat liver. VD3 treatment (twice a week) was started 4 weeks before the 2-AAF regimen and continued throughout the study. Aberrant metaphase chromosomes were counted from the regenerating hepatocytes 15, 30 or 45 weeks after STZ injection, while DNA strand break and adduct assays were performed 45 days post-STZ treatment. Dietary exposure to 2-AAF elicited a substantial increase in CAs and elevated the extent of DNA strand breaks and formation of N-(deoxyguanosin-8-yl)-2-aminofluorene. A promoting effect of STZ was evident from CAs coupled with DNA strand break analysis. VD3 treatment substantially reducted 2-AAF+STZ-induced CAs as well as DNA strand breaks and adducts. Thus, VD3 appears to be effective in suppressing liver-specific early chromosomal as well as DNA damage during the process of rat hepatocarcinogenesis initiated with 2-AAF and promoted by STZ contributing to its promise as a cancer chemotherapeutic agent.
Cell Mol Life Sci 2001 Jul
PMID:1Alpha,25-dihydroxyvitamin D3 inhibits hepatic chromosomal aberrations, DNA strand breaks and specific DNA adducts during rat hepatocarcinogenesis. 1152 6

Intracellular insulin signaling involves a series of alternative and complementary pathways created by the multiple substrates of the insulin receptor (IRS) and the various isoforms of the SH2 domain signaling molecules that can interact with substrate. In this study we investigated IRS-1 and IRS-2 tyrosine phosphorylation, their association with PI3-kinase and the phosphorylation of Akt, a serine-threonine kinase situated downstream to PI 3-kinase, in liver and muscle of two animal models of insulin resistance: 72 h of fasting and STZ-diabetic rats. There was an upregulation in insulin-induced IRS-1 and IRS-2 tyrosine phosphorylation and association with PI3-kinase in liver and muscle of both animal models of insulin resistance. However, Akt phosphorylation showed different regulation, increasing in fasting and decreasing in STZ-diabetic rats. Since an important difference between these two animal models of insulin resistance is the plasma glucose levels, we can suggest that in STZ diabetic rats, the reduction in Akt phosphorylation is probably related to hyperglycemia and may certainly contribute to the molecular mechanism of insulin resistance observed in these animals.
Mol Cell Endocrinol 2001 Oct 25
PMID:Regulation of IRS-2 tyrosine phosphorylation in fasting and diabetes. 1160 26

The PI-3 kinase signalling pathway is an important pathway in mediating the glucoregulatory effects of insulin and skeletal muscle (SKM) is the major tissue involved in glucose utilization. In diabetes this pathway is impaired, either due to lack of insulin as in Type I diabetes, or due to insulin resistance as in Type 2 diabetes. Bis(maltolato)-oxovanadium IV (BMOV), an insulin mimetic/enhancing agent, produces a marked glucose lowering effect in models of both types of diabetes. Some in vitro studies have shown that phosphatidylinositol 3 kinase (PI-3 kinase) activity is enhanced by vanadium. In the present study we looked at changes in PI-3 kinase expression and activity in SKM from STZ-diabetic and fa/fa Zucker rats treated with BMOV for 3 weeks. Although BMOV treatment completely normalized glucose levels in STZ-diabetic rats, no effect was observed on basal or insulin-stimulated PI-3 kinase activity. In fatty Zucker rats, activation of PI-3 kinase activity after insulin injection was impaired as compared to age matched lean controls, but BMOV again did not affect the activity. These results suggest that although PI-3 kinase is an important signalling factor in glucose utilization, vanadium treatment does not reduce hyperglycemia through activation of SKM PI-3 kinase in vivo.
Mol Cell Biochem 2001 Jul
PMID:In vivo effects of vanadium in diabetic rats are independent of changes in PI-3 kinase activity in skeletal muscle. 1168 10

Glucose uptake, glut 4 translocation and activation of protein kinase B were measured in Langendorff perfused hearts from (i) Wistar control, (ii) lean, neonatal Streptozotocin induced (Stz) and (iii) Zucker (fa/fa) obese diabetic rats of 10-12 weeks old. Hearts were subjected to stimulation with insulin, isoproterenol (beta-adrenergic agonist) or a combination of insulin and isoproterenol, during the perfusion protocol. Basal myocardial glucose uptake was impaired in both diabetic models, but could be stimulated significantly by insulin. In the Zucker rats, the time-course of insulin action was delayed. Insulin and beta-stimulation of glucose uptake were not additive. Evaluation of sarcolemmal membranes from these hearts showed that the affinity of glut 4 was significantly lower in the Zucker but not in the Stz hearts while a reduced affinity found with a combination of insulin and beta-stimulation in control hearts, was absent in both diabetic models. Total membrane lysates were analyzed for glut 4 expression while an intracellular component was generated to quantify translocation on stimulation as well as activity of protein kinase B (PKB). At this age, the neonatal Streptozotocin induced diabetic animals presented with more faulty regulation concerning adrenergic stimulated effects on elements of this signal transduction pathway while the Zucker fa/fa animals showed larger deviations in insulin stimulated effects. The overall response of the Zucker myocardium was poorer than that of the Stz group. No significant modulation of beta-adrenergic signaling on insulin stimulated glucose uptake was found. The PI-3-kinase inhibitor wortmannin, could abolish glucose uptake as well as PKB activation elicited by both insulin and isoproterenol.
Mol Cell Biochem 2001 Jul
PMID:The effects of insulin and beta-adrenergic stimulation on glucose transport, glut 4 and PKB activation in the myocardium of lean and obese non-insulin dependent diabetes mellitus rats. 1168 17


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