Publications by authors named "Arindam Bandyopadhyay"

19 Publications

  • Page 1 of 1

Bacopasaponins with cytotoxic activity against human breast cancer cells in vitro.

Mol Biol Rep 2021 Mar 10;48(3):2497-2505. Epub 2021 Apr 10.

Department of Zoology, Visva-Bharati, Santiniketan, West Bengal, 731235, India.

Globally, breast cancer is a serious concern that exhibits a persistent rise in its incidence and related mortality even after significant advancement in the field of cancer research. To find an alternative cure for the disease from natural resources we selected Bacopa monniera, a perennial ethnomedicinal plant popularly used for boosting memory and mental health. We isolated four different types of dammarane saponins, namely bacopasaponins C-F (1-4) from the plant and evaluated their toxic effects on two different types of human breast cancer cell lines-a hormone-responsive MCF7 and a triple-negative MDA-MB-231. Interestingly, MTT assay revealed a dose-dependent toxic effect of all four types of bacopasaponins on both of these cell lines, 4 being the most effective with 48 h-inhibitory concentration (IC) of 32.44 and 30 µM in MCF7 and MDA-MB-231 respectively. Further, 4 caused significant alterations in normal cytomorphology and induction of apoptosis in both of these cell lines after 48 h of treatment. No caspase-8 activity was detected in these cell lines when exposed to 4 for 2, 24, and 48 h; instead, Western blotting analysis confirmed involvement of either caspase-9 (MCF7) or both caspase-9 and caspase-3 (MDA-MB-231) in the process of apoptosis indicating the occurrence of intrinsic mode. Additionally, at comparable effective doses to cancer, bacopasaponins showed much less toxicity in normal human peripheral blood lymphocytes (≥ 85% cell survival). Overall, the findings project bacopasaponin F, a natural constituent of Bacopa monniera, as an efficient and safer alternative for breast cancer therapeutics.
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http://dx.doi.org/10.1007/s11033-021-06284-2DOI Listing
March 2021

Combined effect of arsenic and fluoride at environmentally relevant concentrations in zebrafish (Danio rerio) brain: Alterations in stress marker and apoptotic gene expression.

Chemosphere 2021 Apr 21;269:128678. Epub 2020 Oct 21.

Department of Zoology, Visva-Bharati, Santiniketan, 731235, West Bengal, India. Electronic address:

Arsenic and fluoride are two naturally occurring toxicants to which various organisms including a major part of the human populations are co-exposed to. However, interactions between them inside body are quite complicated and needs proper evaluation. Inconclusive reports regarding their combined effects on brain prompted us to conduct this study where we investigated their individual as well as combined effects on female zebrafish brain at environmentally relevant concentrations (50 μgL arsenic trioxide and 15 mgL sodium fluoride) after different time intervals (15, 30 and 60 days). Persistent near-basal level of GSH, least increased MDA content and catalase activity portrayed arsenic and fluoride co-exposure as less toxic which was corroborated with far less damage caused in the histoarchitecture of optic tectum region in midbrain. Stress-responsive genes viz., Nrf2 and Hsp70 were overexpressed after individual as well as combined exposures, indicating a common cellular response to combat the formed oxidative stresses. Biphasic response of AChE upon individual exposure confirmed their neurotoxic effects too. Expression profile of p53 (unaltered), Bax (lower or near-basal) and Bcl2 (comparatively higher), along with absence of DNA fragmentation indicated no induction of apoptosis in the co-exposed group. Tissue accumulation of arsenic and fluoride was significantly less in the brain of co-exposed zebrafish when compared to their individual exposures. This preliminary study indicates an antagonistic effect of these two toxicants in zebrafish brain and needs further studies involving oxidative stress independent markers to understand the detailed molecular mechanism.
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http://dx.doi.org/10.1016/j.chemosphere.2020.128678DOI Listing
April 2021

Chronic exposure to environmentally relevant concentration of fluoride alters Ogg1 and Rad51 expressions in mice: Involvement of epigenetic regulation.

Ecotoxicol Environ Saf 2020 Oct 11;202:110962. Epub 2020 Jul 11.

Department of Zoology, Visva-Bharati, Santiniketan, 731235, West Bengal, India. Electronic address:

Chronic exposure to fluoride (F) beyond the permissible limit (1.5 ppm) is known to cause detrimental health effects by induction of oxidative stress-mediated DNA damage overpowering the DNA repair machinery. In the present study, we assessed F induced oxidative stress through monitoring biochemical parameters and looked into the effect of chronic F exposure on two crucial DNA repair genes Ogg1 and Rad51 having important role against ROS induced DNA damages. To address this issue, we exposed Swiss albino mice to an environmentally relevant concentration of fluoride (15 ppm NaF) for 8 months. Results revealed histoarchitectural damages in liver, brain, kidney and spleen. Depletion of GSH, increase in lipid peroxidation and catalase activity in liver and brain confirmed the generation of oxidative stress. qRT-PCR result showed that expressions of Ogg1 and Rad51 were altered after F exposure in the affected organs. Promoter hypermethylation was associated with the downregulation of Rad51. F-induced DNA damage and the compromised DNA repair machinery triggered intrinsic pathway of apoptosis in liver and brain. The present study indicates the possible association of epigenetic regulation with F induced neurotoxicity.
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http://dx.doi.org/10.1016/j.ecoenv.2020.110962DOI Listing
October 2020

Environmentally relevant concentration of chromium induces nuclear deformities in erythrocytes and alters the expression of stress-responsive and apoptotic genes in brain of adult zebrafish.

Sci Total Environ 2020 Feb 19;703:135622. Epub 2019 Nov 19.

Department of Zoology, Visva-Bharati, Santiniketan 731235, West Bengal, India. Electronic address:

Heavy metal contamination of water body has become a serious threat to aquatic life forms specially to fish. Hexavalent chromium (Cr [VI]) is one of the most potent heavy metal toxicant. It is present in aquatic environment at concentrations beyond permissible limit. Considering the fact that toxic effects are function of the exposure concentration, studies involving toxicological risk assessment should be done at environmentally relevant concentration. Therefore we studied the toxic effects of Cr [VI] to zebrafish at an environmentally relevant concentration (2 mg L). We monitored the genotoxic potential of Cr [VI] in erythrocytes through a simple reliable microscopic assay and found an increase in frequency of micronucleated erythrocytes along with erythrocytes with blebbed, lobed and notched nuclei. In addition, Cr [VI] induced neurotoxicity, being a least reported event was also investigated. Histological alterations in brain, elevated GSH and MDA content and increased catalase activity indicated oxidative stress-mediated damage. This was further confirmed through expressional alteration of Ucp2. Upregulation of Nrf2, Nqo1 and Ho1 clearly indicated the involvement of Nrf2-ARE system in stress response against Cr [VI] induced neurotoxicity. The transcriptional induction of apoptotic genes such as Bax, Caspase 9 and Caspase 3 along with downregulation of Bcl2 indicated that the cytoprotective system failed to counter the induced stress. Interestingly, there was upregulation of AChE gene, which could be correlated with the upregulated apoptotic genes. This study provides an insight on the neurotoxic stress of Cr [VI] on the zebrafish yet at an environmentally relevant concentration. Moreover the induction of nuclear anomalies in the erythrocytes can serve as extremely sensitive endpoints of toxicological stress indicators of aquatic contaminants like Cr [VI].
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http://dx.doi.org/10.1016/j.scitotenv.2019.135622DOI Listing
February 2020

Mixture effect of arsenic and fluoride at environmentally relevant concentrations in zebrafish (Danio rerio) liver: Expression pattern of Nrf2 and related xenobiotic metabolizing enzymes.

Aquat Toxicol 2019 Aug 3;213:105219. Epub 2019 Jun 3.

Department of Zoology, Visva-Bharati, Santiniketan, 731235, West Bengal, India. Electronic address:

Nrf2 is a crucial transcription factor that regulates the expression of cytoprotective enzymes and controls cellular redox homeostasis. Both arsenic and fluoride are potent toxicants that are known to induce Nrf2. They are reported to coexist in many areas of the world leading to complex mixture effects in exposed organisms. The present study investigated the expression of Nrf2 and related xenobiotic metabolizing enzymes along with other stress markers such as histopathological alterations, catalase activity, reduced glutathione content and lipid peroxidation in zebrafish liver as a function of combined exposure to environmentally relevant concentrations of arsenic (37.87 μgL or 5.05 × 10 M) and fluoride (6.8 mg L or 3.57 × 10 M) for 60 days. The decrease in the total reduced glutathione level was evident in all treatment conditions. Hyperactivity of catalase along with conspicuous elevation in reactive oxygen species, malondialdehyde content and histo-architectural anomalies signified the presence of oxidative stress in the treatment groups. Nrf2 was seen to be induced at both transcriptional and translational levels in case of both individual and co-exposure. The same pattern was observed in case of its nuclear translocation also. From the results of qRT-PCR it was evident that at each time point co-exposure to arsenic and fluoride seemed to alter the gene expression of Cu/Zn Sod, Mn Sod, Gpx and Nqo1 just like their individual exposure but at a very low magnitude. In conclusion, this study demonstrates for the first time the differential expression and activity of Nrf2 and other stress response genes in the zebrafish liver following individual and combined exposure to arsenic and fluoride.
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http://dx.doi.org/10.1016/j.aquatox.2019.06.002DOI Listing
August 2019

Environmentally relevant concentration of chromium activates Nrf2 and alters transcription of related XME genes in liver of zebrafish.

Chemosphere 2019 Jan 18;214:35-46. Epub 2018 Sep 18.

Department of Zoology, Visva-Bharati, Santiniketan-731235, West Bengal, India. Electronic address:

Fish is an excellent model to decipher the mechanism of toxicity of aquatic contaminants such as hexavalent chromium (Cr [VI]). The present study looked into the manifestation of stress in liver of zebrafish exposed to an environmentally relevant concentration (2 mgL), and the functioning of the cytoprotective machinery that pacifies the formed stress. The results lead us to hypothesize that oxidative stress plays a key role in chromium-induced toxicity resulting in lipid peroxidation and extensive changes in tissue ultrastructure. In treated fish, production of reactive oxygen species, increase in reduced glutathione content and increase in malondialdehyde content along with enhanced catalase activity were evident. Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) was found to increase both at transcriptional and translational level and its translocation into the nucleus was confirmed by fluorescence-based immunohistochemical studies. The mRNA levels of genes like Nqo1, Cyp1a and Cu/Zn Sod were found to increase whereas Ho1, Hsp70 and Ucp2 were down-regulated. The sensitivity of these genes towards Cr [VI] validates their candidature as important biomarkers of Cr [VI] exposure in zebrafish.
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http://dx.doi.org/10.1016/j.chemosphere.2018.09.104DOI Listing
January 2019

(Linn.)-mediated green silver nanoparticles trigger caspase 9-dependent cell death in MCF7 and MDA-MB-231 cells.

Breast Cancer (Dove Med Press) 2017 18;9:265-278. Epub 2017 Apr 18.

Molecular Genetics Laboratory, Department of Zoology, Visva-Bharati, Santiniketan, West Bengal.

Introduction: Leaf extract of or mint plant was used as reducing agent for the synthesis of green silver nanoparticles (GSNPs) as a cost-effective, eco-friendly process compared to that of chemical synthesis. The existence of nanoparticles was characterized by ultraviolet-visible spectrophotometry, dynamic light scattering, Fourier transform infrared spectroscopy, X-ray diffraction, energy-dispersive X-ray analysis, atomic-force microscopy and transmission electron microscopy analyses, which ascertained the formation of spherical GSNPs with a size range of 3-9 nm. Anticancer activities against breast cancer cell lines (MCF7 and MDA-MB-231) were studied and compared with those of chemically synthesized (sodium borohydride [NaBH]-mediated) silver nanoparticles (CSNPs).

Materials And Methods: Cell survival of nanoparticle-treated and untreated cells was studied by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay. Cell-cycle analyses were carried out using fluorescence-activated cell sorting. Cell morphology was observed by fluorescence microscopy. Expression patterns of PARP1, P53, P21, Bcl2, Bax and cleaved caspase 9 as well as caspase 3 proteins in treated and untreated MCF7 and MDA-MB-231 cells were studied by Western blot method.

Results: MTT assay results showed that -mediated GSNPs exhibited significant cytotoxicity toward breast cancer cells (MCF7 and MDA-MB-231), which were at par with that of CSNPs. Cell cycle analyses of MCF7 cells revealed a significant increase in sub-G1 cell population, indicating cytotoxicity of GSNPs. On the other hand, human peripheral blood lymphocytes showed significantly less cytotoxicity compared with MCF7 and MDA-MB-231 cells when treated with the same dose. Expression patterns of proteins suggested that GSNPs triggered caspase 9-dependent cell death in both cell lines. The Ames test showed that GSNPs were nonmutagenic in nature.

Conclusion: GSNPs synthesized using may be considered as a promising anticancer agent in breast cancer therapy. They are less toxic and nonmutagenic and mediate caspase 9-dependent apoptosis in MCF7 and MDA-MB-231 cells.
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http://dx.doi.org/10.2147/BCTT.S130952DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5402903PMC
April 2017

Congenital Plasmodium vivax malaria and intracranial hemorrhage.

Indian J Pediatr 2014 Sep 10;81(9):959-60. Epub 2013 Oct 10.

Department of Pediatric Medicine, Dr B. C. Roy Postgraduate Institute of Pediatric Sciences, 111, Narkeldanga Main Road, Kolkata, India,

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http://dx.doi.org/10.1007/s12098-013-1252-zDOI Listing
September 2014

An unusual case of recurrent stridor in a child.

J Indian Med Assoc 2013 Jan;111(1):65-6

Department of Paediatrics. Calcutta National Medical College, Kolkata, India.

A two-year-old child presented with history recurrent attacks of stridor. Initially he was thought to have laryngomalasia and treated accordingly but the symptoms did not improve with age. The child was symptomatic only during episodes of respiratory tract infection. There was no feeding difficulty, growth was normal. CT thorax showed moderate compression of trachea just above the carina. CT angiography showed an incomplete double aortic arch. As the child was symptomatic only during intercurrent infections and there was no feeding difficulty, respiratory distress and growth problems conservative management was opted. Parents were advised to observe the patient and review after six months.
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January 2013

Unusual association of epidemic dropsy with brachial neuritis and palatal palsy.

Indian J Pediatr 2013 May 10;80(5):428-9. Epub 2012 Jan 10.

Department of Pediatric Medicine, Dr. B C Roy Postgraduate Institute of Pediatric Sciences, Kolkata, India.

Epidemic dropsy (ED) results from accidental ingestion of adulterated mustard oil with argemone oil. Chief organs involved in this disease are heart, subcutaneous tissue, eyes and kidneys. Nervous system involvement is very rare. Objective manifestation of neurological involvement is even rarer. The authors report two cases from the same family, who were victims of epidemic dropsy along with their parents. One of them showed objective neurologic involvement in the form of brachial neuritis and another showed palatal palsy.
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http://dx.doi.org/10.1007/s12098-011-0676-6DOI Listing
May 2013

Insulin suppresses endotoxin-induced oxidative, nitrosative, and inflammatory stress in humans.

Diabetes Care 2010 Nov 10;33(11):2416-23. Epub 2010 Aug 10.

Division of Endocrinology, Diabetes and Metabolism, State University of New York at Buffalo and Kaleida Health, Buffalo, New York, USA.

Objective: To investigate whether insulin reduces the magnitude of oxidative, nitrosative, and inflammatory stress and tissue damage responses induced by endotoxin (lipopolysaccharide [LPS]).

Research Design And Methods: Nine normal subjects were injected intravenously with 2 ng/kg LPS prepared from Escherichia coli. Ten others were infused with insulin (2 units/h) for 6 h in addition to the LPS injection along with 100 ml/h of 5% dextrose to maintain normoglycemia.

Results: LPS injection induced a rapid increase in plasma concentrations of nitric oxide metabolites, nitrite and nitrate (NOM), and thiobarbituric acid-reacting substances (TBARS), an increase in reactive oxygen species (ROS) generation by polymorphonuclear leukocytes (PMNLs), and marked increases in plasma free fatty acids, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), macrophage migration inhibition factor (MIF), C-reactive protein, resistin, visfatin, lipopolysaccharide binding protein (LBP), high mobility group-B1 (HMG-B1), and myoglobin concentrations. The coinfusion of insulin led to a total elimination of the increase in NOM, free fatty acids, and TBARS and a significant reduction in ROS generation by PMNLs and plasma MIF, visfatin, and myoglobin concentrations. Insulin did not affect TNF-α, MCP-1, IL-6, LBP, resistin, and HMG-B1 increases induced by the LPS.

Conclusions: Insulin reduces significantly several key mediators of oxidative, nitrosative, and inflammatory stress and tissue damage induced by LPS. These effects of insulin require further investigation for its potential use as anti-inflammatory therapy for endotoxemia.
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http://dx.doi.org/10.2337/dc10-0929DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2963505PMC
November 2010

Frequent occurrence of hypogonadotropic hypogonadism in type 2 diabetes.

J Clin Endocrinol Metab 2004 Nov;89(11):5462-8

Division of Endocrinology, Diabetes, and Metabolism, State University of New York at Buffalo and Kaleida Health, Buffalo, New York 14209, USA.

Type 2 diabetes is associated with lower total testosterone (T) levels in cross-sectional studies. However, it is not known whether the defect is primary or secondary. We investigated the prevalence of hypogonadism in type 2 diabetes by measuring serum total T, free T (FT), SHBG, LH, FSH, and prolactin (PRL) in 103 type 2 diabetes patients. FT was measured by equilibrium dialysis. FT was also calculated by using T and SHBG (cFT). Hypogonadism was defined as low FT or cFT. The mean age was 54.7 +/- 1.1 yr, mean body mass index (BMI) was 33.4 +/- 0.8 kg/m(2), and mean HbA1c was 8.4 +/- 0.2%. The mean T was 12.19 +/- 0.50 nmol/liter (351.7 +/- 14.4 ng/dl), SHBG was 27.89 +/- 1.65 nmol/liter, and FT was 0.250 +/- 0.014 nmol/liter. Thirty-three percent of patients were hypogonadal. LH and FSH levels were significantly lower in the hypogonadal group compared with patients with normal FT levels (3.15 +/- 0.26 vs. 3.91 +/- 0.24 mIU/ml for LH and 4.25 +/- 0.45 vs. 5.53 +/- 0.40 mIU/ml for FSH; P < 0.05). There was a significant inverse correlation of BMI with FT (r = -0.382; P < 0.01) and T (r = -0.327; P < 0.01). SHBG correlated inversely with BMI (r = -0.267; P < 0.05) but positively with age (r = 0.538; P < 0.001) and T (r = 0.574; P < 0.001). FT correlated strongly with cFT (r = 0.919; P < 0.001) but not with SHBG. LH levels correlated positively with FT (r = 0.287; P < 0.05). We conclude that hypogonadotropic hypogonadism occurs commonly in type 2 diabetes.
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http://dx.doi.org/10.1210/jc.2004-0804DOI Listing
November 2004

Glucose intake induces an increase in activator protein 1 and early growth response 1 binding activities, in the expression of tissue factor and matrix metalloproteinase in mononuclear cells, and in plasma tissue factor and matrix metalloproteinase concentrations.

Am J Clin Nutr 2004 Jul;80(1):51-7

Division of Endocrinology, Diabetes and Metabolism, State University of New York at Buffalo, and Kaleida Health, 14209, USA.

Background: Glucose intake has been shown to cause an increase in intranuclear nuclear factor-kappa B and a decrease in inhibitor kappa B that are consistent with a proinflammatory effect. We investigated the effect of glucose intake on 2 other proinflammatory transcription factors, activator protein 1 (AP-1) and early growth response 1 (Egr-1), and on the genes regulated by them, ie, the genes for matrix metalloproteinases 2 (MMP-2) and 9 (MMP-9) and tissue factor (TF), respectively.

Objective: The objective of the study was to ascertain whether the intake of 75 g glucose induces an increase in AP-1, Egr-1, and the genes regulated by them.

Design: Eight healthy subjects were given 75 g glucose dissolved in 300 mL water to drink. Blood samples were collected before and 1, 2, and 3 h after glucose intake. Four weeks later, the same subjects were given 300 mL water sweetened with saccharine, and blood samples were collected at the same time points. Mononuclear cells (MNCs) were separated, and nuclear fractions were isolated.

Results: AP-1 and Egr-1 binding activities were significantly higher 1 and 2 h after glucose intake and then decreased toward the baseline by 3 h. The expression of MMP-2 and TF in MNC homogenates also was significantly higher at 2 and 3 h. Plasma concentrations of MMP-2 were significantly higher at 3 h, whereas those of MMP-9 were significantly higher at 1, 2, and 3 h. In addition, TF was significantly higher at 2 and 3 h. Intake of saccharine-sweetened water had no significant effect on the inflammatory mediators measured in this study.

Conclusion: Glucose induces proinflammatory changes, including increases in AP-1, Egr-1, MMPs, and TF, the factors that regulate processes that are potentially relevant to atherosclerotic plaque rupture and thrombosis.
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http://dx.doi.org/10.1093/ajcn/80.1.51DOI Listing
July 2004

Anti-inflammatory and profibrinolytic effect of insulin in acute ST-segment-elevation myocardial infarction.

Circulation 2004 Feb 2;109(7):849-54. Epub 2004 Feb 2.

Division of Endocrinology, Diabetes and Metabolism, State University of New York at Buffalo, and Kaleida Health, Buffalo, NY 14209, USA.

Background: The clinical benefits of insulin previously observed in acute ST-segment-elevation myocardial infarction (STEMI) may be partially explained by an anti-inflammatory effect. We assessed this potential effect of insulin in STEMI patients treated with fibrinolytics.

Methods And Results: Thirty-two patients receiving reteplase were randomly assigned infusions of either insulin at 2.5 U/h, dextrose, and potassium (GIK) or normal saline and potassium (C) for 48 hours. Plasma concentrations of high-sensitivity C-reactive protein (CRP), serum amyloid A (SAA), plasminogen activator inhibitor-1 (PAI-1), creatine kinase (CK), and CK-MB were measured at baseline and sequentially for 48 hours. Total p47phox protein in mononuclear cells was measured in a subgroup of 13 subjects. Baseline CRP and SAA were significantly increased (2- to 4-fold) at 24 and 48 hours in each group (P<0.01). However, in the insulin group, there was a significant (P<0.05) attenuation of the absolute rise in concentration of CRP and SAA from baseline. The absolute increase of CRP and SAA was reduced by 40% (CRP) and 50% (SAA) at 24 hours and at 48 hours compared with the control group. The absolute increase in PAI-1 from baseline and the percentage increase in p47phox over 48 hours were significantly (P<0.05) lower in the insulin-treated group. CK-MB peaked earlier and tended to be lower in insulin-treated subjects, especially in patients with inferior MI.

Conclusions: Insulin has an anti-inflammatory and profibrinolytic effect in patients with acute MI. These effects may contribute to the clinical benefits of insulin in STEMI.
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http://dx.doi.org/10.1161/01.CIR.0000116762.77804.FCDOI Listing
February 2004

Inflammation: the link between insulin resistance, obesity and diabetes.

Trends Immunol 2004 Jan;25(1):4-7

Division of Endocrinology, Diabetes and Metabolism, State University of New York at Buffalo and Kaleida Health, 3 Gates Circle, Buffalo, NY 14209, USA.

Recent data have revealed that the plasma concentration of inflammatory mediators, such as tumour necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6), is increased in the insulin resistant states of obesity and type 2 diabetes, raising questions about the mechanisms underlying inflammation in these two conditions. It is also intriguing that an increase in inflammatory mediators or indices predicts the future development of obesity and diabetes. Two mechanisms might be involved in the pathogenesis of inflammation. Firstly, glucose and macronutrient intake causes oxidative stress and inflammatory changes. Chronic overnutrition (obesity) might thus be a proinflammatory state with oxidative stress. Secondly, the increased concentrations of TNF-alpha and IL-6, associated with obesity and type 2 diabetes, might interfere with insulin action by suppressing insulin signal transduction. This might interfere with the anti-inflammatory effect of insulin, which in turn might promote inflammation.
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http://dx.doi.org/10.1016/j.it.2003.10.013DOI Listing
January 2004

Insulin suppresses plasma concentration of vascular endothelial growth factor and matrix metalloproteinase-9.

Diabetes Care 2003 Dec;26(12):3310-4

Division of Endocrinology, Diabetes and Metabolism, State University of New York at Buffalo, Buffalo, New York, USA.

Objective: We recently demonstrated a potent anti-inflammatory and thus a potential antiatherogenic effect of insulin in human aortic endothelial cells and mononuclear cells at physiologically relevant concentrations. We have now further investigated the anti-inflammatory suppressive action of insulin on vascular endothelial growth factor (VEGF) and matrix metalloproteinase (MMP)-9. VEGF and MMP-9 play a central regulatory role in angiogenesis, contribute to the pathogenesis of proliferative retinopathy, and have also been found to accelerate atherosclerosis.

Research Design And Methods: Insulin was infused (2 IU/h) in 5% dextrose (100 ml/h) and KCl (8 mmol/h) into 10 fasting, obese, nondiabetic subjects for 4 h. Subjects were also infused with 5% dextrose without insulin and with saline on two separate occasions. Blood samples were obtained at 0, 2, 4, and 6 h.

Results: Plasma insulin concentrations increased from a basal level of 12.5 +/- 2.2 to 28.2 +/- 3.3 micro U/ml at 2 h and 24.4 +/- 3.7 micro U/ml at 4 h after insulin infusion. VEGF concentration decreased from 307.2 +/- 163.8 pg/ml (100%) at 0 h to 73.5 +/- 20.9% of the basal level at 2 h and 67.1 +/- 23.2% at 4h. Plasma MMP-9 concentrations decreased from 375 +/- 196.3 ng/ml (100%) at 0 h to 83 +/- 22% of the basal level at 2 h and to 82 +/- 21% of the basal level at 4 h (P < 0.05). Dextrose infusion alone did not change plasma VEGF concentration. However, plasma MMP-9 concentration increased significantly at 4 h following dextrose infusion alone (P < 0.05). Saline infusions without insulin caused no alteration in glucose, insulin, VEGF, or MMP-9.

Conclusions: These observations may have implications for a potential antiretinopathic and antiatherosclerotic effect of insulin in the long term.
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http://dx.doi.org/10.2337/diacare.26.12.3310DOI Listing
December 2003

The potential influence of inflammation and insulin resistance on the pathogenesis and treatment of atherosclerosis-related complications in type 2 diabetes.

J Clin Endocrinol Metab 2003 Jun;88(6):2422-9

Division of Endocrinology, Diabetes and Metabolism, State University of New York at Buffalo and Kaleida Health, Buffalo, New York 14209, USA.

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http://dx.doi.org/10.1210/jc.2003-030178DOI Listing
June 2003

The potential therapeutic role of insulin in acute myocardial infarction in patients admitted to intensive care and in those with unspecified hyperglycemia.

Diabetes Care 2003 Feb;26(2):516-9

Division of Endocrinology, Diabetes and Metabolism, State University of New York at Buffalo and Kaleida Health, USA.

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http://dx.doi.org/10.2337/diacare.26.2.516DOI Listing
February 2003