Biomedical subjects

N Venkatesan

Publications and source records attributed to N Venkatesan.

At least 37 records · Page 2Linked to original sources

PubMed1998

Glycoprotein composition in cyclophosphamide-induced lung fibrosis.

The present study investigated the glycosylation state of proteins in lung tissue of a cyclophosphamide-induced model of pulmonary fibrosis in rats. In fibrotic lung, the carbohydrate constituents (total hexose, fucose, sialic acid and hexosamine) of salt-soluble, collagenase, elastase and papain digested glycoproteins were significantly higher compared to normal lungs. Interestingly, fibrotic lung tissues had higher activities of mannosyl, glucosyl, galactosyl, sialyl and fucosyl transferases than normal lung tissues. Similarly, mannosyl, glucosyl, galactosyl, sialyl and fucosyl transferases were higher in serum from rats with fibrosis than in that from normals. These data indicate that glycoprotein metabolism is significantly altered from normal in animals with interstitial lung fibrosis.

Animals↗

PubMed1998

Inhibition of cell proliferation in head and neck squamous cell carcinoma cell lines with antisense cyclin D1.

Cyclin D1 and cyclin G are essential regulatory factors in the progression of the cell cycle from G0 through G1 and S phase. Aberrations in expression of these cyclins may lead to dysregulated cellular proliferation that could result in neoplasia. Amplification and overexpression of cyclin D1 have been observed in many human cancers, whereas cyclin G is a new cyclin recently described in osteosarcoma cells. This study was performed to determine whether these cyclins were amplified in head and neck squamous cell carcinoma (HNSCC) tumors. Polymerase chain reaction of DNA extracted from 22 HNSCC primary tumors and three HNSCC cell lines did not reveal amplification of cyclin D1 in any of the tumor samples. Southern blot analysis identified amplification of cyclin D1 in a single tumor. Amplification of cyclin G was not observed in any of the tumors by Southern blot hybridization with a cyclin G probe. HNSCC cell lines transfected with antisense cyclin D1 were tested for cell proliferation by the incorporation of 3H-thymidine into cells grown in serum-free media. By 72 hours of incubation, there was a greater than 30% reduction in proliferation of cells transfected with antisense cyclin D1 as compared with non-transfected control cells. The results indicate that cyclin D1 may play an important role in the growth and proliferation of HNSCC cells.

Adult↗

PubMed1998

Curcumin attenuation of acute adriamycin myocardial toxicity in rats.

The protective effect of curcumin on acute adriamycin (ADR) myocardial toxicity was analysed in rats. ADR toxicity, induced by a single intraperitoneal injection (30 mg kg(-1)), was revealed by elevated serum creatine kinase (CK) and lactate dehydrogenase (LDH). The level of the lipid peroxidation products, conjugated dienes and malondialdehyde, was markedly elevated by ADR. ADR caused a decrease in myocardial glutathione content and glutathione peroxidase activity. In contrast, cardiac catalase activity was increased in ADR rats. Curcumin treatment (200 mg kg(-1), seven days before and two days following ADR) significantly ameliorated the early manifestation of cardiotoxicity (ST segment elevation and an increase in heart rate) and prevented the rise in serum CK and LDH exerted by ADR. ADR rats that received curcumin displayed a significant inhibition of lipid peroxidation and augmentation of endogenous antioxidants. These results suggest that curcumin inhibits ADR cardiotoxicity and might serve as novel combination chemotherapeutic agent with ADR to limit free radical-mediated organ injury.

Animals↗

PubMed1998

Discoidal niosome based controlled ocular delivery of timolol maleate.

Non-ionic surface active agents based discoidal vesicles (discomes) bearing timolol maleate were prepared. Niosomes were incorporated with Solulan C24 in order to effect vesicle to discome transition. The discomes were relatively large in size, 12-60 microm. They were found to entrap a relatively high quantity of timolol maleate. The prepared system characterized for size, shape and drug release profile in vitro. They were found to release the contents following biphasic profile particularly in the case where the drug was loaded using a pH gradient technique. The prepared system could produce or sustain a suitable activity profile upon administration into the ocular cavity; however, systemic absorption was minimized to a negliable level. The discomes were found to be promising and of potential for controlled ocular administration of water-soluble drugs.

Administration, Topical↗

PubMed1997

Curcumin protects bleomycin-induced lung injury in rats.

The present study was designed to determine the protective effects of curcumin against bleomycin (BLM)-induced inflammatory and oxidant lung injury. The data indicate that BLM-mediated lung injury resulted in increases in lung lavage fluid biomarkers such as total protein, angiotensin-converting enzyme (ACE), lactate dehydrogenase (LDH), N-acetyl-beta-D-glucosaminidase (NAG), lipid peroxidation (LPO) products, superoxide dismutase (SOD) and catalase. Bleomycin administration also resulted in increased levels of malondialdehyde (MDA) in bronchoalveolar lavage fluid (BALF) and bronchoalveolar lavage (BAL) cells and greater amounts of alveolar macrophage (AM) superoxide dismutase activity. By contrast, lower levels of reduced glutathione (GSH) were observed in lung lavage fluid, BAL cells and AM. Stimulated superoxide anion and hydrogen peroxide release by AM from BLM rats were found to be higher. Curcumin treatment resulted in a significant reduction in lavage fluid biomarkers. In addition, curcumin treatment resulted in the restoration of antioxidant status in BLM rats. These data suggest that curcumin treatment reduces the development of BLM-induced inflammatory and oxidant activity. Therefore, curcumin offers the potential for a novel pharmacological approach in the suppression of drug or chemical-induced lung injury.

Acetylglucosaminidase↗

PubMed1997

Protection by taurine against adriamycin-induced proteinuria and hyperlipidemia in rats.

Taurine was used in the present study to evaluate its beneficial effects against proteinuria and hyperlipidemia associated with nephrotic syndrome. Rats made nephrotic with adriamycin had a high excretion of protein, albumin, and N-acetyl-beta-D-glucosaminidase compared with nonnephrotic rats. Nephrotic rats manifested hyperlipidemia with significant elevation in all major lipoprotein fractions. Treatment with taurine significantly suppressed adriamycin-induced proteinuria, albuminuria, and urinary excretion of N-acetyl-beta-D-glucosaminidase. Treatment of rats wit taurine for 7 days before adriamycin, and daily thereafter, significantly lowered plasma cholesterol, triglycerides, phospholipids, lipid peroxides, and malondialdehyde associated with lipoprotein fractions. Similarly, total lipids, cholesterol, triglycerides, lipid peroxides, hydroperoxides, and hydroxyl radicals in the liver and kidneys of taurine-treated adriamycin rats were decreased significantly compared with adriamycin alone. Lecithin cholesterol acyl transferase activity and free fatty acid levels in plasma, lipoprotein lipase activity, glutathione, total thiol, and ascorbic acid in the liver and the kidneys of taurine-treated adriamycin groups were significantly elevated compared with adriamycin alone. These results suggest that taurine might be applicable as a protective agent for proteinuria and hyperlipidemia associated with nephrotic syndrome.

Acetylglucosaminidase↗

PubMed1996

Factor XII-induced mitogenesis is mediated via a distinct signal transduction pathway that activates a mitogen-activated protein kinase.

Clotting factor XII (Hageman factor) contains epidermal growth factor (EGF)-homologous domains and is reported to be a potent mitogen for human hepatoma (HepG2) cells. In this study, we tested whether factor XII exhibits growth factor activity on several other EGF-sensitive target cells, including fetal hepatocytes, endothelial cells, alveolar type II cells, and aortic smooth muscle cells. We found that factor XII significantly enhanced [3H]thymidine incorporation in aortic smooth muscle cells (SMCs) and all other cells tested. Tyrphostin, a growth factor receptor/tyrosine kinase antagonist, inhibited both EGF- and factor XII-induced responses. However, differences in the levels of magnitude of DNA synthesis, the observed synergism between EGF and factor XII, and the differential sensitivity to tyrphostin suggest that the EGF receptor and the factor XII receptor may be nonidentical. The factor XII-induced mitogenic response was achieved at concentrations that were 1/10th the physiologic range for the circulating factor and was reduced by popcorn inhibitor, a specific factor XII protease inhibitor. Treatment of aortic SMCs with factor XII, as well as activated factor XII, resulted in a rapid and transient activation of a mitogen-activated/extracellular signal-regulated protein kinase with peak activity/tyrosine phosphorylation observed at 5 to 10 min of exposure. Taken together, these data (i) confirm that clotting factor XII functions as a mitogenic growth factor and (ii) demonstrate that factor XII activates a signal transduction pathway, which includes a mitogen-activated protein kinase.

Animals↗

PubMed1996

Dexamethasone-induced impairment in skeletal muscle glucose transport is not reversed by inhibition of free fatty acid oxidation.

Our previous studies suggested a possible role for the glucose-free fatty acid (FFA) cycle, ie, preferential utilization of FFA by muscle at the expense of glucose, in dexamethasone (DEX)-induced insulin resistance. To determine whether this resistance could be reversed by inhibiting FFA utilization, we used etomoxir, a potent inhibitor of mitochondrial FFA oxidation. Male Sprague-Dawley rats were injected subcutaneously with 1 mg/kg DEX or the vehicle every other day for 10 days, and half of each group was administered 10 mg/kg etomoxir by gavage once per day and 1 hour before the experiment. As expected, etomoxir treatment increased serum FFA levels and inhibited FFA oxidation by diaphragm in vitro. Administration of etomoxir decreased serum glucose and insulin concentrations under basal conditions in both control and DEX-treated animals, implying enhanced insulin sensitivity. DEX treatment significantly increased endogenous glucose production and decreased whole-body glucose disposal, as well as 2-deoxyglucose (2-DG) uptake by skeletal muscle during euglycemic-hyperinsulinemic clamps. Administration of etomoxir led to small but significant increases in glucose disposal rates of both control (14%) and DEX (23%) groups, but had no effect on residual endogenous glucose production. Thus, DEX-induced insulin resistance was marginally ameliorated but not completely reversed by etomoxir. Depressed 2-DG uptake by individual muscle tissues observed in the present study in conjunction with the absence of free intracellular glucose in muscle tissue following glucose-insulin infusion strongly suggests that the primary defect in glucose metabolism is at the level of transport. Neither overall abundance of the insulin-sensitive glucose transporter (GLUT-4) in skeletal muscle nor its distribution between intracellular stores and plasma membrane were modified by DEX treatment, either, under basal conditions or in response to acute insulin stimulus. These results suggest a defect(s) in the inherent activity of plasma membrane-bound GLUT-4 as the likely mechanism for DEX-induced insulin resistance.

Animals↗

PubMed1995

Modulation of cyclophosphamide-induced early lung injury by curcumin, an anti-inflammatory antioxidant.

Cyclophosphamide causes lung injury in rats through its ability to generate free radicals with subsequent endothelial and epithelial cell damage. In order to observe the protective effects of a potent anti-inflammatory antioxidant, curcumin (diferuloyl methane) on cyclophosphamide-induced early lung injury, healthy, pathogen free male Wistar rats were exposed to 20 mg/100 g body weight of cyclophosphamide, intraperitoneally as a single injection. Prior to cyclophosphamide intoxication oral administration of curcumin was performed daily for 7 days. At various time intervals (2, 3, 5 and 7 days post insult) serum and lung samples were analyzed for angiotensin converting enzyme, lipid peroxidation, reduced glutathione and ascorbic acid. Bronchoalveolar lavage fluid was analyzed for biochemical constituents. The lavage cells were examined for lipid peroxidation and glutathione content. Excised lungs were analyzed for antioxidant enzyme levels. Biochemical analyses revealed time course increases in lavage fluid total protein, albumin, angiotensin converting enzyme (ACE), lactate dehydrogenase, N-acetyl-beta-D-glucosaminidase, alkaline phosphatase, acid phosphatase, lipid peroxide levels and decreased levels of glutathione (GSH) and ascorbic acid 2, 3, 5 and 7 days after cyclophosphamide intoxication. Increased levels of lipid peroxidation and decreased levels of glutathione and ascorbic acid were seen in serum, lung tissue and lavage cells of cyclophosphamide groups. Serum angiotensin converting enzyme activity increased which coincided with the decrease in lung tissue levels. Activities of antioxidant enzymes were reduced with time in the lungs of cyclophosphamide groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1995

Insulin resistance in rats harboring growth hormone-secreting tumors: decreased receptor number but increased kinase activity in liver.

Growth hormone (GH) is a potent antagonist of insulin action, and this resistance occurs primarily at a post-binding step(s). To elucidate the underlying mechanisms, the effects of chronic GH excess on the structure and function of insulin receptors partially purified from the liver were examined in rats harboring GH-secreting tumors. Insulin resistance was established in this animal model of GH hypersecretion by a hyperinsulinemic euglycemic clamp. Specific binding of 125I-insulin and receptor number were reduced in tumor animals by 40% and 62%, respectively, reflecting downregulation of the insulin receptor by hyperinsulinemia in these animals. Receptors from tumor animals showed a 50% increase in beta-subunit phosphorylation and in the kinase activity toward the synthetic polypeptide Glu4:Tyr1 when measured in vitro in the absence of insulin; however, the incremental stimulation by insulin (170 nmol/L) of the phosphorylation of either the beta-subunit or Glu4:Tyr1 was not different between control and experimental animals. There was no difference between the two groups in Glu4:Tyr1 phosphorylation measured after immunodepletion of receptors by antibodies to the insulin receptor, indicating that the observed alteration in the kinase activity of tumor animals was intrinsic to the insulin receptor. Exposure to chronic GH excess did not alter insulin receptor structure, as evidenced by electrophoretic mobility under reducing and nonreducing conditions. The enhanced basal kinase activity of the receptor from tumor animals may reflect a more highly phosphorylated state of the receptor (and hence elevated enzyme activity) in these animals due to elevated serum insulin levels. These results demonstrate that the hepatic insulin resistance in rats chronically exposed to GH excess is not due to impaired insulin receptor kinase activity.

Animals↗

PubMed1995

Differential regulation of glucose transport and glucose transporter (GLUT-1) gene expression by vanadate, phorbol ester and okadaic acid in L6 skeletal muscle cells.

Vanadate, an inhibitor of protein tyrosine phosphatases (PTPases), elicited time-and-dose-dependent increases in glucose transport in rat muscle L6 cells in culture: the rate was increased by 150-175% over control in 24 h at 75-100 microM. In contrast, molybdate, another inhibitor of PTPases, failed to stimulate glucose transport. The effect of vanadate was not blocked by tyrosine kinase inhibitors, genistein or tyrphostin RG 50864, implying that tyrosine kinase activation may not mediate the action of vanadate. The ability of vanadate to stimulate glucose transport was preserved in cells whose protein kinase C (PKC) activity was down-regulated by prior exposure to phorbol esters (TPA), suggesting that the vanadate effect was unrelated to the TPA-sensitive PKC isoform(s). Okadaic acid, an inhibitor of protein phosphatases 1 and 2A, was a potent activator of glucose transport increasing the rate 7-fold in 24 h at a concentration of 50 nM. The increases in GLUT-1 mRNA level in response to vanadate and TPA were paralleled bh much smaller increases in immunoreactive GLUT-1 protein level, whereas okadaic acid treatment markedly elevated GLUT-1 protein without a concomitant change in GLUT-1 mRNA levels.

Animals↗

PubMed1994

In vivo administration of taurine and niacin modulate cyclophosphamide-induced lung injury.

The antiinflammatory, antioxidant activity of taurine and niacin against cyclophosphamide-induced early lung injury in rats was investigated. A single intraperitoneal injection of cyclophosphamide markedly altered the levels of several biomarkers in bronchoalveolar lavage fluid: total protein, albumin, angiotensin converting enzyme, lactate dehydrogenase, lactate, N-acetyl-beta-D-glucosaminidase, alkaline phosphatase, acid phosphatase and lipid peroxidation product were significantly elevated. In contrast, decreased levels of total reduced glutathione (GSH) and ascorbic acid were observed. Cyclophosphamide significantly increased malondialdehyde levels in serum and lung. Significant increases in lung content of lipid hydroperoxides were seen that paralleled the decreased levels of total reduced glutathione and total sulfhydryl groups. Pretreatment of rats with daily intraperitoneal injection of taurine plus niacin 7 days prior to and 2 days after cyclophosphamide insult significantly inhibited the development of lung injury, prevented the alterations in lavage fluid biomarkers associated with inflammatory reactions, with less lipid peroxidation and restoration of antioxidants. In conclusion, our results suggest that taurine and niacin in combination is efficient in blunting cyclophosphamide-induced pulmonary damage.

Acid Phosphatase↗

PubMed1994

Cyclophosphamide induced early biochemical changes in lung lavage fluid and alterations in lavage cell function.

The present investigation evaluated the changes in bronchoalveolar lavage fluid (BALF) biochemical constituents and indices of bronchoalveolar lavage cell functions to detect early lung injury in rats following intraperitoneal administration of cyclophosphamide (CP). Rats were exposed to a single intraperitoneal injection of CP (200 or 300 mg/kg body weight). Experimental and control rats were sacrificed at various time intervals (2, 3, 5, 7, 11, 21, and 42 days after cessation of exposure), and lung lavage was performed to examine several markers of lung injury. Biochemical analyses revealed dose-related increases in BALF angiotensin converting enzyme activity, total protein, lactate, lactate dehydrogenase, and N-acetyl-beta-D-glucosaminidase (NAG) levels on days 2, 3, 5, 7, and dose-related increases in albumin, alkaline phosphatase, acid phosphatase, and lipid peroxidation on days 2, 3, 5, 7, and 11 after CP treatment. In contrast, reduced levels of ascorbic acid and glutathione (GSH) content were observed in lung lavage fluid. We also examined bronchoalveolar lavage cells for acid hydrolases (acid phosphatase, beta-glucuronidase, NAG) and GSH content. Activity of acid hydrolases was slightly elevated on day 2 and peaked on days 3, 5, and 7. However, lavage cell GSH content was decreased. Thus, measurements of pulmonary changes by analyzing lavage fluid and lavage cell functions seems to be a useful marker for assessing the early onset and development of CP-induced lung injury.

Animals↗

PubMed1994

Phenobarbital treatment enhances insulin-mediated glucose metabolism and improves lipid metabolism in the diabetic rat.

Previous studies with healthy volunteers and non-insulin-dependent diabetic (NIDDM) patients have shown a strong association between overall glucose metabolism and hepatic microsomal enzyme activity. In this study, the effects of 10-day oral administration of phenobarbital (PB), a potent inducer of the hepatic microsomal mixed-function oxidase system, on carbohydrate and lipid metabolism in the basal state and on glucose kinetics during submaximal hyperinsulinemic (5 mU.kg-1.min-1 insulin) clamps were investigated in nondiabetic rats and in rats made diabetic by the intravenous (IV) administration of either low-dose (40 mg/kg) or high-dose (55 mg/kg) streptozocin (STZ). In control rats receiving PB in drinking water (0.5 mg/mL), serum insulin and triglyceride levels were diminished without any change in glucose and cholesterol concentrations in the fed state. Administration of PB in drinking water (0.25 mg/mL) to both groups of diabetic rats decreased their water intake and serum triglyceride levels in the absence of an effect on glucose, insulin, and cholesterol concentrations in the fed state. However, fasting serum glucose levels and basal glucose turnover rates were lower in both groups of diabetic rats receiving PB. PB treatment increased the heparin-releasable lipoprotein lipase (LPL) activity of epididymal fat in both control and low-dose diabetic groups; this was not assessed in the high-dose diabetic group. Neither peripheral glucose utilization nor hepatic glucose production during submaximal insulin clamps was modified by PB treatment in nondiabetic rats. In contrast, PB administration enhanced insulin-mediated peripheral glucose utilization, as well as suppression of hepatic glucose production, in both low-dose and high-dose diabetic groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue↗

PubMed1994

Impaired glucose transport in skeletal muscle but normal GLUT-4 tissue distribution in glucose-infused rats.

This study was undertaken to determine if glucose toxicity in normal rats caused decreased whole body insulin-stimulated glucose disposal and in vivo impaired muscle glucose transport and, if so, whether it was mediated by changes in GLUT-4 content or tissue distribution. Rats were infused with 50% dextrose for 48 h after which they were clamped and injected with 2-deoxy-D-[3H]glucose. Hindlimb muscles were removed for measurement of uptake of radioactivity (glucose transport) and GLUT-4 levels in total, plasma and internal membrane fractions. Dextrose infusions caused significant hyperglycemia [15.5 +/- 1.4 vs. 6.7 +/- 0.3 (SE) mM], hyperinsulinemia [678 +/- 108 vs. 168 +/- 42 (SE) pM], and depressed insulin-mediated whole body glucose disposal [12.8 +/- 2.0 vs. 47.0 +/- 10.6 (SE) mg glucose.kg-1.min-1.pmol insulin-1.1(-1) x 10(3)]. Muscle glucose transport (ng.min-1.mg tissue-1) was significantly decreased in biceps (4.0 +/- 0.6 vs. 13.4 +/- 2.5), gastrocnemius (4.6 +/- 1.1 vs. 12.9 +/- 2.2), and plantaris (5.5 +/- 0.7 vs. 17.5 +/- 3.6) muscles compared with saline-infused rats. The difference in the soleus muscle (13.2 +/- 1.6 vs. 19.4 +/- 2.7) did not quite reach statistical significance. There were no differences in total, plasma, or internal membrane GLUT-4 content between the two groups. It is concluded that glucose toxicity causes impaired insulin-stimulated glucose transport, probably due to decreased activity of GLUT-4.

4-Nitrophenylphosphatase↗

PubMed1994

Molecular cloning of the human CAK1 gene encoding a cyclin-dependent kinase-activating kinase.

Cyclin-dependent, proline-directed protein kinases normally function to execute critical cell cycle transitions; abnormal expression and/or viral subversion of the positive (cyclins) and negative (Pic1) regulatory subunits may contribute to neoplastic transformation and tumorigenesis. In addition to the binding of regulatory subunits, the enzymatic activities of the cyclin-dependent kinases, Cdc2 and Cdk2, are tightly regulated by site-specific protein phosphorylation events. Recent studies have identified a critical phosphorylation site (Thr-161) located within kinase Subdomain VIII that is necessary for Cdc2 activation, and enzymatic activities capable of carrying out this heterologous phosphorylation event have been detected in both Xenopus oocytes and human somatic cells. In this report, we characterize by molecular cloning a human homologue of the Xenopus Cdk-activating kinase (Cak, encoded by MO15); the novel human gene is designated (HS)CAK1. While only 75% identity is observed at the nucleotide level, the deduced amino acid sequence encoded by (HS)CAK1 is approximately 87% identical to that of the Xenopus MO15 gene in corresponding regions. The catalytic domain of (HS)Cak1, defined by conserved kinase Subdomains I through XI, exhibits considerable homology with (HS)Cdc2, suggesting that this kinase cascade involves closely related enzymes. Immunological studies with anti-Cak antibodies confirm the presence of specific immunoreactivity in highly purified preparations of the human Cdc2-activating kinase. The molecular characterization of (HS)CAK1 should facilitate studies of its physiological regulation, as well as its potential utility as a target for therapeutic intervention in the treatment of proliferative disorders.

Amino Acid Sequence↗

PubMed1993

Angiotensin I converting enzyme activity in adriamycin induced nephrosis in rats.

Activity of the dipeptidyl hydrolase angiotensin converting enzyme (ACE) has been observed to be altered by treatment with adriamycin (ADR). We used an animal model of ADR nephrotoxicity to study the effects on ACE in serum, urine and tissues on days 5, 10, 15, 20, 25 and 30 after ADR administration. Both glomerular and tubular injury occurred as evidenced by heavy proteinuria, albuminuria and increased urine N-acetyl glucosaminidase (NAG) excretion. Serum ACE was significantly elevated on days 20, 25 and 30. Of great interest was the excretion of ACE in urine of treated rats which ran parallel with the total protein excretion above the barely detectable levels found in controls. ACE activity increased in kidney, adrenal gland and liver on days 15, 20, 25 and 30. Heart and brain ACE levels increased on days 25 and 30. Increased ACE activity in aorta and lungs occurred on days 20, 25 and 30. ACE activity decreased in kidney, aorta, heart and brain on days 5 and 10. These observations strongly suggest a contribution of various tissues to elevate the serum ACE level. Urinary ACE may be of potential use as an index for renal glomerular and tubular damage.

Animals↗

PubMed1991

Antidiabetic action of vanadyl in rats independent of in vivo insulin-receptor kinase activity.

The effects of oral vanadyl sulfate administration for 9-12 days on carbohydrate and lipid metabolism in the basal state and on glucose dynamics during submaximal hyperinsulinemic clamps were investigated in nondiabetic and streptozocin-induced diabetic rats. Decreases in growth rate and water and food consumption were the only significant alterations noted in control animals receiving vanadyl. Administration of vanadyl to diabetic rats resulted in weight loss; a significant decrease in plasma glucose, triglyceride, and cholesterol levels; and decreases in food and water intake, without a concomitant change in plasma insulin concentrations. Vanadyl treatment did not modify either peripheral glucose utilization or hepatic glucose production in control rats during submaximal insulin clamps. In contrast, vanadyl therapy increased insulin-induced glucose utilization significantly and had a small but nonsignificant effect on insulin-mediated suppression of glucose production in diabetic rats. The tyrosine kinase activity of liver- and muscle-derived insulin receptors from diabetic rats that underwent clamp study, which reflected the in vivo phosphorylation state of insulin receptor, was not altered by vanadyl treatment. In conclusion, these results show that augmentation of peripheral glucose utilization is the major determinant of the antidiabetic action of vanadyl and support the notion that the action of vanadyl is independent of insulin-receptor kinase activity.

Animals↗