scholarly journals Plasma paraoxonase1 activity in rats treated with monocrotophos: a study of the effect of duration of exposure

2019 ◽  
Vol 12 (3) ◽  
pp. 129-135
Author(s):  
Raju Nagaraju ◽  
Apurva Kumar R. Joshi ◽  
Sowmya Giriyapura Vamadeva ◽  
Rajini Padmanabhan Sharda
Keyword(s):  
Insulin Resistance ◽  
Early Phase ◽  
Chronic Exposure ◽  
Prolonged Exposure ◽  
Plasma Cholinesterase ◽  
Pon1 Activity ◽  
Plasma Parameters ◽  
Glucose Levels

Abstract We have earlier demonstrated the potential of monocrotophos (MCP), a highly toxic organophosphorus insecticide (OPI), to elicit insulin resistance in rats after chronic exposure. Given the understanding of role of paraoxonase1 (PON1) in OPI toxicity and diabetes pathology, this study was envisaged to understand the effect of duration of exposure to MCP on plasma PON1 activity in rats. Rats were administered MCP per os at 1/20 and 1/10th LD50 as daily doses for 180 days. Interim blood samples were collected at 15, 30, 45, 90 and 180 d for analysis of plasma parameters. Exposure to MCP for 45 resulted in persistent trend of hyperinsulinemia, while significant increase in fasting glucose levels was observed after 180 days. MCP caused suppression of plasma cholinesterase activity though the study period, albeit extent of inhibition was more severe during the early phase of the study. Exposure to MCP for 180 d resulted in hypertriglyceridemia and marginal decrease in HDL-C levels. MCP failed to modulate PON1 activity in plasma during the early phase of the study (up to 45 d). However, prolonged exposure resulted in significant increase in the plasma PON1 activity. This suggests that manifestation of insulin resistance in rats subjected to chronic exposure to MCP is associated with increase in PON1 activity. Our work provides rationale for studying whether the increase in PON1 activity observed in the present study serves to counter the deleterious effect of long term exposure to organophosphorus insecticides on metabolic homeostasis.

Effect of chronic exposure to monocrotophos on white adipose tissue in rats and its association with metabolic dyshomeostasis

2020 ◽  
Vol 39 (9) ◽  
pp. 1190-1199
Author(s):  
R Nagaraju ◽  
AKR Joshi ◽  
S Vamadeva ◽  
PS Rajini
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
White Adipose Tissue ◽  
Chronic Exposure ◽  
Fatty Acid Synthase ◽  
Necrosis Factor Alpha ◽  
Lipin 1 ◽  
Factor Alpha ◽  
Acetyl Coenzyme A Carboxylase

Earlier, we demonstrated that chronic exposure to monocrotophos (MCP) elicits insulin resistance in rats along with increased white adipose tissue (WAT) weights. This study was carried out to delineate the biochemical and molecular changes in adipose tissues of rats subjected to chronic exposure to MCP (0.9 and 1.8 mg/kg bw/d for 180 days). Pesticide-treated rats exhibited increased fasting glucose and hyperinsulinemia as well as dyslipidemia. Tumor necrosis factor-alpha and leptin levels were elevated, while adiponectin level was suppressed in plasma of treated rats. MCP treatment caused discernable increase in the weights of perirenal and epididymal WAT. Acetyl coenzyme A carboxylase, fatty acid synthase, glyceraldehyde-3-phosphate dehydrogenase, lipin-1, and lipolytic activities were elevated in the WAT of MCP-treated rats. Corroborative changes were observed in the expression profile of proteins that are involved in lipogenesis and adipose tissue differentiation. Our results clearly demonstrate that long-term exposure to organophosphorus insecticides (OPIs) such as MCP has far-reaching consequences on metabolic health as evidenced by the association of adipogenic outcomes with insulin resistance, hyperinsulinemia, endocrine dysregulations, and dyslipidemia. Taken together, our results suggest that long-term exposure to OPI may be a risk factor for metabolic dysregulations.

Long-term AT1 receptor blockade improves metabolic function and provides renoprotection in Fischer-344 rats

2007 ◽  
Vol 293 (3) ◽  
pp. H1327-H1333 ◽  
Author(s):  
Shea Gilliam-Davis ◽  
Valerie S. Payne ◽  
Sherry O. Kasper ◽  
Ellen N. Tommasi ◽  
Michael E. Robbins ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Control Group ◽  
Receptor Blockade ◽  
Ang Ii ◽  
Glucose Levels ◽  
Fischer 344 ◽  
Young Rats ◽  
Age Related ◽  
F344 Rats

Fischer-344 (F344) rats exhibit proteinuria and insulin resistance in the absence of hypertension as they age. We determined the effects of long-term (1 yr) treatment with the angiotensin (ANG) II type 1 (AT1) receptor blocker L-158,809 on plasma and urinary ANG peptide levels, systolic blood pressure (SBP), and indexes of glucose metabolism in 15-mo-old male F344 rats. Young rats at 3 mo of age ( n = 8) were compared with two separate groups of older rats: one control group ( n = 7) and one group treated with L-158,809 ( n = 6) orally (20 mg/l) for 1 yr. SBP was not different between control and treated rats but was higher in young rats. Serum leptin, insulin, and glucose levels were comparable between treated and young rats, whereas controls had higher glucose and leptin with a similar trend for insulin. Plasma ANG I and ANG II were higher in treated than untreated young or older rats, as evidence of effective AT1 receptor blockade. Urinary ANG II and ANG-(1-7) were higher in controls compared with young animals, and treated rats failed to show age-related increases. Protein excretion was markedly lower in treated and young rats compared with control rats (young: 8 ± 2 mg/day vs. control: 129 ± 51 mg/day vs. treated: 9 ± 3 mg/day, P < 0.05). Long-term AT1 receptor blockade improves metabolic parameters and provides renoprotection. Differential regulation of systemic and intrarenal (urinary) ANG systems occurs during blockade, and suppression of the intrarenal system may contribute to reduced proteinuria. Thus, insulin resistance, renal injury, and activation of the intrarenal ANG system during early aging in normotensive animals can be averted by renin-ANG system blockade.

scholarly journals Emerging Links between Cadmium Exposure and Insulin Resistance: Human, Animal, and Cell Study Data

Toxics ◽  
2020 ◽  
Vol 8 (3) ◽  
pp. 63
Author(s):  
Aleksandra Buha ◽  
Danijela Đukić-Ćosić ◽  
Marijana Ćurčić ◽  
Zorica Bulat ◽  
Biljana Antonijević ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Study Data ◽  
Current Evidence ◽  
Target Tissue ◽  
Insulin Production ◽  
Β Cells ◽  
Glucose Levels ◽  
Human Animal

Recent research has helped clarify the role of cadmium (Cd) in various pathological states. We have demonstrated Cd involvement in pancreatic cancer, as well as the bioaccumulation of Cd in the pancreas. Bioaccumulation and increased toxicity suggest that Cd may also be involved in other pancreas-mediated diseases, like diabetes. Cd falls into the category of “hyperglycemic” metals, i.e., metals that increase blood glucose levels, which could be due to increased gluconeogenesis, damage to β-cells leading to reduced insulin production, or insulin resistance at target tissue resulting in a lack of glucose uptake. This review addresses the current evidence for the role of Cd, leading to insulin resistance from human, animal, and in vitro studies. Available data have shown that Cd may affect normal insulin function through multiple pathways. There is evidence that Cd exposure results in the perturbation of the enzymes and modulatory proteins involved in insulin signal transduction at the target tissue and mutations of the insulin receptor. Cd, through well-described mechanisms of oxidative stress, inflammation, and mitochondrial damage, may also alter insulin production in β-cells. More work is necessary to elucidate the mechanisms associated with Cd-mediated insulin resistance.

scholarly journals Fasting Normoglycemia after Intravenous Thrombolysis Predicts Favorable Long-Term Outcome in Non-Diabetic Patients with Acute Ischemic Stroke

2021 ◽  
Vol 10 (14) ◽  
pp. 3005
Author(s):  
Marcin Wnuk ◽  
Justyna Derbisz ◽  
Leszek Drabik ◽  
Maciej Malecki ◽  
Agnieszka Slowik
Keyword(s):  
Ischemic Stroke ◽  
Fasting Glucose ◽  
Intravenous Thrombolysis ◽  
Favorable Outcome ◽  
Diabetic Patients ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Glucose Levels

Background: Only a few studies evaluated the role of fasting glucose levels after intravenous thrombolysis (IVT) in patients with acute ischemic stroke (AIS). Importantly, formal analysis concerning the prognostic role of fasting glucose levels in these patients with and without diabetes mellitus (DM) was not performed. Therefore, we assessed whether fasting normoglycemia (FNG) next morning after AIS treated with IVT was associated with 90-day functional outcome in diabetic and non-diabetic patients. Methods: We retrospectively analyzed 362 AIS patients treated with IVT at The University Hospital in Krakow. FNG was defined as glucose below 5.5 mmol/L. A favorable outcome was defined as modified Rankin score (mRS) of 0–2 at day 90 after AIS onset. Results: At 3-month follow-up, FNG was associated with favorable outcome (87.5% vs. 60.8%, p < 0.001) and decreased risk of death (3.1% vs. 18.1%, p = 0.002). Independent predictors of a favorable outcome for the whole group were: younger age (HR 0.92, 95%CI 0.89–0.95), lower NIHSS score after IVT (HR 0.70, 95%CI 0.65–0.76), lower maximal systolic blood pressure within 24 h after IVT (HR 0.92, 95%CI 0.89–0.95) and FNG (HR 4.12, 95%CI 1.38–12.35). Association between FNG and mortality was found in univariable (HR 1.47, 95%CI 0.04–0.62) but not in multivariable analysis (HR 0.23, 95%CI 0.03–1.81). In subgroup analyses, FNG was an independent predictor of favorable outcome (HR 5.96, 95%CI 1.42–25.1) only in patients without DM. Conclusions: FNG next morning after IVT is an independent protective factor for a favorable long-term outcome in non-diabetic AIS patients.

scholarly journals Nociceptive pain and anxiety in equines: Physiological and behavioral alterations

2021 ◽  
pp. 2984-2995
Author(s):  
I. Hernández-Avalos ◽  
D. Mota-Rojas ◽  
J. E. Mendoza-Flores ◽  
A. Casas-Alvarado ◽  
K. Flores-Padilla ◽  
...  
Keyword(s):  
Heart Rate ◽  
Prolonged Exposure ◽  
Activity Index ◽  
Emotional States ◽  
Blood Biomarkers ◽  
Behavioral Alterations ◽  
Glucose Levels ◽  
Multiple Factors

Pain and anxiety are two of the most important concerns in clinical veterinary medicine because they arise as consequences of multiple factors that can severely affect animal welfare. The aim of the present review was to provide a description and interpretation of the physiological and behavioral alterations associated with pain and anxiety in equines. To this end, we conducted an extensive review of diverse sources on the topic. The article begins by describing the neurophysiological pathway of pain, followed by a discussion of the importance of the limbic system in responses to pain and anxiety, since prolonged exposure to situations that cause stress and pain generates such physiological changes as tachycardia, tachypnea, hypertension, hyperthermia, and heart rate variability (HRV), often accompanied by altered emotional states, deficient rest, and even aggressiveness. In the long term, animals may show deficiencies in their ability to deal with changes in the environment due to alterations in the functioning of their immune, nervous, and endocrinologic systems. In conclusion, pain and anxiety directly impact the homeostasis of organisms, so it is necessary to conduct objective evaluations of both sensations using behavioral scales, like the horse grimace scale, complemented by assessments of blood biomarkers to analyze their correlation with physiological parameters: Heart rate, respiratory rate, HRV, the parasympathetic tone activity index, lactate and glucose levels, and temperature. Additional tools – infrared thermography, for example – can also be used in these efforts to improve the quality of life and welfare of horses.

scholarly journals The role of polycarbonate monomer bisphenol-A in insulin resistance

PeerJ ◽  
2017 ◽  
Vol 5 ◽  
pp. e3809 ◽  
Author(s):  
Milos Pjanic
Keyword(s):  
Insulin Resistance ◽  
Bisphenol A ◽  
Chronic Exposure ◽  
Endocrine System ◽  
Human Populations ◽  
Human Society ◽  
Environmental Distribution ◽  
Peripheral Tissues ◽  
Wide Range

Bisphenol A (BPA) is a synthetic unit of polycarbonate polymers and epoxy resins, the types of plastics that could be found in essentially every human population and incorporated into almost every aspect of the modern human society. BPA polymers appear in a wide range of products, from liquid storages (plastic bottles, can and glass linings, water pipes and tanks) and food storages (plastics wraps and containers), to medical and dental devices. BPA polymers could be hydrolyzed spontaneously or in a photo- or temperature-catalyzed process, providing widespread environmental distribution and chronic exposure to the BPA monomer in contemporary human populations. Bisphenol A is also a xenoestrogen, an endocrine-disrupting chemical (EDC) that interferes with the endocrine system mimicking the effects of an estrogen and could potentially keep our endocrine system in a constant perturbation that parallels endocrine disruption arising during pregnancy, such as insulin resistance (IR). Gestational insulin resistance represents a natural biological phenomenon of higher insulin resistance in peripheral tissues of the pregnant females, when nutrients are increasingly being directed to the embryo instead of being stored in peripheral tissues. Gestational diabetes mellitus may appear in healthy non-diabetic females, due to gestational insulin resistance that leads to increased blood sugar levels and hyperinsulinemia (increased insulin production from the pancreatic beta cells). The hypothesis states that unnoticed and constant exposure to this environmental chemical might potentially lead to the formation of chronic low-level endocrine disruptive state that resembles gestational insulin resistance, which might contribute to the development of diabetes. The increasing body of evidence supports the major premises of this hypothesis, as exemplified by the numerous publications examining the association of BPA and insulin resistance, both epidemiological and mechanistic. However, to what extent BPA might contribute to the development of diabetes in the modern societies still remains unknown. In this review, I discuss the chemical properties of BPA and the sources of BPA contamination found in the environment and in human tissues. I provide an overview of mechanisms for the proposed role of bisphenol A in insulin resistance and diabetes, as well as other related diseases, such as cardiovascular diseases. I describe the transmission of BPA effects to the offspring and postulate that gender related differences might originate from differences in liver enzyme levels, such as UDP-glucuronosyltransferase, which is involved in BPA processing and its elimination from the organism. I discuss the molecular mechanisms of BPA action through nuclear and membrane-bound ER receptors, non-monotonic dose response, epigenetic modifications of the DNA and propose that chronic exposure to weak binders, such as BPA, may mimic the effects of strong binders, such as estrogens.

scholarly journals Epigenetics of Hepatic Insulin Resistance

2021 ◽  
Vol 12 ◽  
Author(s):  
Hannah Maude ◽  
Claudia Sanchez-Cabanillas ◽  
Inês Cebola
Keyword(s):  
Gene Expression ◽  
Insulin Resistance ◽  
Prolonged Exposure ◽  
Current Knowledge ◽  
Hepatic Insulin Resistance ◽  
Metabolic Dysfunction ◽  
Post Translational Modifications ◽  
Targeted Interventions ◽  
Insulin Resistant

Insulin resistance (IR) is largely recognized as a unifying feature that underlies metabolic dysfunction. Both lifestyle and genetic factors contribute to IR. Work from recent years has demonstrated that the epigenome may constitute an interface where different signals may converge to promote IR gene expression programs. Here, we review the current knowledge of the role of epigenetics in hepatic IR, focusing on the roles of DNA methylation and histone post-translational modifications. We discuss the broad epigenetic changes observed in the insulin resistant liver and its associated pathophysiological states and leverage on the wealth of ‘omics’ studies performed to discuss efforts in pinpointing specific loci that are disrupted by these changes. We envision that future studies, with increased genomic resolution and larger cohorts, will further the identification of biomarkers of early onset hepatic IR and assist the development of targeted interventions. Furthermore, there is growing evidence to suggest that persistent epigenetic marks may be acquired over prolonged exposure to disease or deleterious exposures, highlighting the need for preventative medicine and long-term lifestyle adjustments to avoid irreversible or long-term alterations in gene expression.

The proteolysis of insulin-like growth factor binding proteins in ovine uterine luminal fluid

1998 ◽  
Vol 10 (4) ◽  
pp. 309 ◽  
Author(s):  
A. J. Peterson ◽  
A. M. Ledgard ◽  
S. C. Hodgkinson
Keyword(s):  
Growth Factor ◽  
Binding Proteins ◽  
Prolonged Exposure ◽  
Insulin Like Growth Factor ◽  
Factor Binding ◽  
Late Luteal Phase ◽  
Reduced Activity ◽  
Igfbp 3

During days 12–15 after oestrus (day 0), the uterine luminal fluid (ULF) of both pregnant and non-pregnant ewes contains only two prominent insulin-like growth factor binding proteins (IGFBPs) of 16–18 kDa and 22–24 kDa which preferentially bind IGF-2. Immunoblotting with an IGFBP-3 antibody revealed these to be proteolytic fragments of IGFBP-3. In contrast, the ULF from anoestrus and ovariec-tomized ewes contained intact IGFBP-3 (40–44 kDa) and IGFBP-2 (34 kDa). Co-incubation of ULF from an anoestrus ewe with that from a day 12 cycling ewe cleaved the IGFBP-3 present into the two lower molec-ular weight IGFBPs characteristic of ewes in the late luteal phase of the oestrous cycle. The variation in pro-teolytic activity both during the year and during the cycle suggested an influence of progesterone. Supplementation of progesterone to long-term ovariectomized ewes via a CIDR-G™ breeding device for 5, 10 or 15 days induced marked proteolytic activity in all 10-day treated sheep. The ULF from the 15-day treated ewes showed reduced activity and could inhibit the activity present in 10-day ULF, suggesting the induction of an inhibitor after prolonged exposure to progesterone treatment. A possible role of IGFBP-3 proteolysis in the ovine ULF may be to selectively increase the bioavailability of IGF-1 in the uterine microenvironment, which may be crucial for the rapid elongation of trophoblast that begins during days 12–15 after mating.

Stress Aggravates High-Fat-Diet-Induced Insulin Resistance via a Mechanism That Involves the Amygdala and Is Associated with Changes in Neuroplasticity

2018 ◽  
Vol 107 (2) ◽  
pp. 147-157 ◽  
Author(s):  
Sheng-Feng Tsai ◽  
Hung-Tsung Wu ◽  
Pei-Chun Chen ◽  
Yun-Wen Chen ◽  
Megan Yu ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
High Fat Diet ◽  
Tissue Expansion ◽  
Plasma Corticosterone ◽  
High Fat ◽  
Obesity In Mice ◽  
Bilateral Lesions

Background: The notion that exposure to chronic stress predisposes individuals to developing type 2 diabetes (T2D) has gained much attention in recent decades. Long-term stress induces neuroadaptation in the amygdala and increases corticosterone levels. Corticosterone, the major stress hormone in rodents, induces insulin resistance and obesity in mice. However, little is known about whether the stress-induced amygdalar neuroadaptation could promote the risk of T2D. Methods: We used an 11-week high-fat diet (HFD) feeding paradigm to induce insulin dysfunction in mice, followed by implementation of a 10-day social defeat (SD) stress protocol. Results: Mice receiving SD at the beginning of the HFD feeding aggravated HFD-induced insulin resistance and white adipose tissue expansion. HFD mice had higher levels of plasma corticosterone, which was not affected by the SD. The SD stress upregulated the expression of TrkB and synaptotagmin-4 in the amygdala of HFD mice. Bilateral lesions of the central amygdalae before SD stress inhibited the stress-induced aggravating effect without affecting the HFD-induced elevation of plasma corticosterone. Conclusions: Stress aggravates HFD-induced insulin resistance and neuroadaptation in the amygdala. The HFD-induced insulin resistance is amygdala-dependent. Understanding the role of stress-induced amygdalar adaptation in the development of T2D could inform therapies aimed at reducing chronic stressors to decrease the risk for T2D.

scholarly journals Progressive development of insulin resistance phenotype in male mice with complete aromatase (CYP19) deficiency

2003 ◽  
Vol 176 (2) ◽  
pp. 237-246 ◽  
Author(s):  
K Takeda ◽  
K Toda ◽  
T Saibara ◽  
M Nakagawa ◽  
K Saika ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Blood Glucose ◽  
Serum Triglyceride ◽  
Male Mice ◽  
Wild Type ◽  
Glucose Levels ◽  
Cholesterol Levels ◽  
Blood Glucose Levels ◽  
Body Weights

Aromatase (CYP19) is a cytochrome P450 enzyme that catalyzes the formation of aromatic C18 estrogens from C19 androgens. It is expressed in various tissues and contributes to sex-specific differences in cellular metabolism. We have generated aromatase-knockout (ArKO) mice in order to study the role of estrogen in the regulation of glucose metabolism. The mean body weights of male ArKO (-/-) mice (n=7) and wild-type littermates (+/+) (n=7) at 10 and 12 weeks of age were 26.7+/-1.9 g vs 26.1+/-0.8 g and 28.8+/-1.4 g vs 26.9+/-1.0 g respectively. The body weights of the ArKO and wild-type mice diverged between 10 and 12 weeks of age with the ArKO males weighing significantly more than their wild-type littermates (P<0.05). The ArKO males showed significantly higher blood glucose levels during an intraperitoneal glucose tolerance test compared with wild-type littermates beginning at 18 weeks of age. By 24 weeks of age, they had higher fasting blood glucose levels compared with wild-type littermates (133.8+/-22.8 mg/dl vs 87.8+/-20.3 mg/dl respectively; P<0.01). An intraperitoneal injection of insulin (0.75 mU insulin/g) caused a continuous decline in blood glucose levels in wild-type mice whereas ArKO males at 18 weeks and older exhibited a rebound increase in glucose levels 30 min after insulin injection. Thus, ArKO male mice appear to develop glucose intolerance and insulin resistance in an age-dependent manner. There was no difference in fasting serum triglyceride and total cholesterol levels between ArKO male mice and wild-type littermates at 13 and 25 weeks of age. However, serum triglyceride and cholesterol levels were significantly elevated following a meal in ArKO mice at 36 weeks of age. Serum testosterone levels in ArKO male mice were continuously higher compared with wild-type littermates. Treatment of ArKO males with 17beta-estradiol improved the glucose response as measured by intraperitoneal glucose and insulin tolerance tests. Treatment with fibrates and thiazolidinediones also led to an improvement in insulin resistance and reduced androgen levels. As complete aromatase deficiency in man is associated with insulin resistance, obesity and hyperlipidemia, the ArKO mouse may be a useful animal model for examining the role of estrogens in the control of glucose and lipid homeostasis.

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