scholarly journals Intensive insulin treatment induces insulin resistance in diabetic rats by impairing glucose metabolism-related mechanisms in muscle and liver

2011 ◽  
Vol 211 (1) ◽  
pp. 55-64 ◽  
Author(s):  
Maristela Mitiko Okamoto ◽  
Gabriel Forato Anhê ◽  
Robinson Sabino-Silva ◽  
Milano Felipe dos Santos Ferreira Marques ◽  
Helayne Soares Freitas ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Insulin Sensitivity ◽  
Phosphoenolpyruvate Carboxykinase ◽  
Glucose Transporter ◽  
Glycogen Storage ◽  
Diabetic Rats ◽  
Diabetic Patients ◽  
Good Glycemic Control ◽  
Insulin Sensitizer ◽  
Neutral Protamine Hagedorn

Insulin replacement is the only effective therapy to manage hyperglycemia in type 1 diabetes mellitus (T1DM). Nevertheless, intensive insulin therapy has inadvertently led to insulin resistance. This study investigates mechanisms involved in the insulin resistance induced by hyperinsulinization. Wistar rats were rendered diabetic by alloxan injection, and 2 weeks later received saline or different doses of neutral protamine Hagedorn insulin (1.5, 3, 6, and 9 U/day) over 7 days. Insulinopenic-untreated rats and 6U- and 9U-treated rats developed insulin resistance, whereas 3U-treated rats revealed the highest grade of insulin sensitivity, but did not achieve good glycemic control as 6U- and 9U-treated rats did. This insulin sensitivity profile was in agreement with glucose transporter 4 expression and translocation in skeletal muscle, and insulin signaling, phosphoenolpyruvate carboxykinase/glucose-6-phosphatase expression and glycogen storage in the liver. Under the expectation that insulin resistance develops in hyperinsulinized diabetic patients, we believe insulin sensitizer approaches should be considered in treating T1DM.

scholarly journals Magnesium upregulates insulin receptor and glucose transporter-4 in streptozotocin-nicotinamide-induced type-2 diabetic rats

2018 ◽  
Vol 52 (1) ◽  
pp. 6-16 ◽  
Author(s):  
Ayodele Olufemi Morakinyo ◽  
Titilola Aderonke Samuel ◽  
Daniel Abiodun Adekunbi
Keyword(s):  
Insulin Resistance ◽  
Insulin Sensitivity ◽  
Glucose Tolerance ◽  
Glucose Transporter ◽  
Diabetic Rats ◽  
Glucose Transporter 4 ◽  
Magnesium Supplementation ◽  
Glucose Levels ◽  
Type 2 Diabetic

Abstract Objective. We investigated the effects of magnesium supplementation on glucose tolerance, insulin sensitivity, oxidative stress as well as the concentration of insulin receptor and glucose transporter-4 in streptozotocin-nicotinamide induced type-2 diabetic (T2D) rats. Methods. Rats were divided into four groups designated as: 1) control (CTR); 2) diabetic untreated (DU); 3) diabetic treated with 1 mg of Mg/kg diet (Mg1-D); and 4) diabetic treated with 2 mg of Mg/kg diet (Mg2-D). T2D was induced with a single intraperitoneal (i.p.) injection of freshly prepared streptozotocin (55 mg/kg) aft er an initial i.p. injection of nicotinamide (120 mg/kg). Glucose tolerance, insulin sensitivity, lipid profile, malondialdehyde (MAD) and glutathione content, insulin receptors (INSR) and glucose transporter-4 (GLUT4), fasting insulin and glucose levels were measured, and insulin resistance index was calculated using the homeostatic model assessment of insulin resistance (HOMA-IR). Results. Magnesium supplementation improved glucose tolerance and lowered blood glucose levels almost to the normal range. We also recorded a noticeable increase in insulin sensitivity in Mg-D groups when compared with DU rats. Lipid perturbations associated T2D were significantly attenuated by magnesium supplementation. Fasting glucose level was comparable to control values in the Mg-D groups while the HOMA-IR index was significantly lower compared with the DU rats. Magnesium reduced MDA but increased glutathione concentrations compared with DU group. Moreover, INSR and GLUT4 levels were elevated following magnesium supplementation in T2D rats. Conclusion. These findings demonstrate that magnesium may mediate effective metabolic control by stimulating the antioxidant defense, and increased levels of INSR and GLUT4 in diabetic rats.

scholarly journals Protein Feeding Promotes Redistribution of Endogenous Glucose Production to the Kidney and Potentiates Its Suppression by Insulin

Endocrinology ◽  
2009 ◽  
Vol 150 (2) ◽  
pp. 616-624 ◽  
Author(s):  
Bruno Pillot ◽  
Maud Soty ◽  
Amandine Gautier-Stein ◽  
Carine Zitoun ◽  
Gilles Mithieux
Keyword(s):  
Insulin Sensitivity ◽  
Glucose Uptake ◽  
Phosphoenolpyruvate Carboxykinase ◽  
Glucose Production ◽  
Glycogen Storage ◽  
Endogenous Glucose Production ◽  
Diabetic Patients ◽  
Type 2 Diabetic Patients ◽  
Protein Feeding ◽  
Endogenous Glucose

The aim of this study was to assess in rats the effect of protein feeding on the: 1) distribution of endogenous glucose production (EGP) among gluconeogenic organs, and 2) repercussion on the insulin sensitivity of glucose metabolism. We used gene expression analyses, a combination of glucose tracer dilution and arteriovenous balance to quantify specific organ release, and hyperinsulinemic euglycemic clamps to assess EGP and glucose uptake. Protein feeding promoted a dramatic induction of the main regulatory gluconeogenic genes (glucose-6 phosphatase and phosphoenolpyruvate carboxykinase) in the kidney, but not in the liver. As a consequence, the kidney glucose release was markedly increased, compared with rats fed a normal starch diet. Protein feeding ameliorated the suppression of EGP by insulin and the sparing of glycogen storage in the liver but had no effect on glucose uptake. Combined with the previously reported induction of gluconeogenesis in the small intestine, the present work strongly suggests that a redistribution of glucose production among gluconeogenic organs might occur upon protein feeding. This phenomenon is in keeping with the improvement of insulin sensitivity of EGP, most likely involving the hepatic site. These data shed a new light on the improvement of glucose tolerance, previously observed upon increasing the amount of protein in the diet, in type 2 diabetic patients. Protein feeding increases kidney gluconeogenesis without increasing global endogenous glucose production, and improves insulin suppression of the latter, likely at the hepatic site.

scholarly journals Antihyperglycemic, insulin-sensitivity and anti-hyperlipidemic potential of Ganoderma lucidum, a dietary mushroom, on alloxan- and glucocorticoid-induced diabetic Long-Evans rats

2015 ◽  
Vol 5 (12) ◽  
pp. 450 ◽  
Author(s):  
Md. Moklesur Rahman Sarker
Keyword(s):  
Insulin Sensitivity ◽  
Plasma Glucose ◽  
Ganoderma Lucidum ◽  
Density Lipoprotein ◽  
Diabetic Rats ◽  
Lipoprotein Cholesterol ◽  
Diabetic Patients ◽  
Insulin Sensitizer ◽  
Glucose Levels ◽  
Long Evans

Background: Reishi (Ganoderma lucidum) is a well-known and popular edible mushroom eaten as vegetables all over the world. It has been used as alternative medicine for long years in China, Korea, Japan, Malaysia, and in eastern Russia. It is reported to exhibit a number of medicinal properties including antitumor, antioxidant, immunomodulating, anti-inflammatory, hepatoprotective, and hypoglycemic activities due to the presence of bioactive polysaccharide. Glucocorticoids, prescribed for the treatment of arthritis to protect inflammation and reduce pain, can induce hyperglycemia or aggravate the hyperglycemic condition reaching to very high glucose levels in diabetic patients. However, no report has been published for its activity on glucocorticoid-induced diabetes. Objective: To investigate the effect of Ganoderma lucidum on alloxan- and glucocorticoid- induced diabetes in Long-Evans rats.   Methods: Alloxan monohydrate (150 mg/kg) was intraperitoneally administered to Long-Evans rats as a single dose. The same volume of normal saline was injected to control rats. Three days after alloxan injection, rats with plasma glucose levels higher than 12 mmoL /L were considered as diabetic and they were included in the study. Reishi mushroom was collected from the Mushroom Development Institute, Ministry of Agriculture, Savar, Dhaka, Bangladesh, where it was identified by a Taxonomist. Petroleum ether extract (PEE) Methanol extract (ME) were prepared by maceration and distillation techniques. The extracts were orally administered once in a day at doses of 200, 400, 600 and 800 mg/kg, respectively for 7 days. Metformin (150 mg/kg) was orally administered as a standard antidiabetic drug. Glucose levels were measured at 0 and 7th days of treatment. The rats were allowed to rest for 1 week without treatment. The animals were again injected with dexamethasone (2 mg/kg) through intra-muscular route for 3 days and glucose levels were monitored regularly. Rats were then further treated with PEE and ME and metformin for another 7 days and glucose levels were determined at 0 and 7th days of treatment. Results: The PEE and ME of Reishi mushroom dose-dependently reduced the plasma glucose levels in alloxan-and steroid-induced fasting diabetic rats. The maximum reduction of fasting plasma glucose levels observed by PEE (800 mg/kg) and ME (800 mg/kg) were 55.57% and 36.01% in alloxan-induced and 51.41% and 32.02% in steroid-induced diabetic rats, respectively. Whereas, metformin (150 mg/kg) resulted in the diminution of fasting blood glucose levels by 60.02 and 51.12% in the alloxan- induced and steroid-induced diabetic rats, respectively. Both the PEE (800 mg/kg) and ME (800 mg/kg) significantly   augmented plasma insulin levels (***P < 0.001 and **P < 0.01) and reduced HbA1c (**P < 0.01 and *P < 0.05) in alloxan-and steroid-induced diabetic rats. Besides, treatment of diabetic rats with PEE (800 mg/kg) and ME (800 mg/kg) controlled the 2-h post prandial elevated glucose levels in blood plasma. The same dose of the extracts also significantly reduced the levels of total cholesterol (TC) (***P < 0.001 and ***P < 0.01), triglyceride (TG) (***P < 0.001 and **P < 0.01) and low-density lipoprotein-cholesterol (LDL-c) (***P < 0.001 and ***P < 0.001), as well as increased the level of high density lipoprotein cholesterol (HDL-c) (**P < 0.01 and **P < 0.01, respectively).        Conclusion: Our study demonstrated that edible mushrooms-Reishi has antihyperglycemic, insulin-sensitivity, and hyperlipidaemic activity against both alloxan- and corticosteroid-induced diabetes rats. The bioactive chemicals responsible for those activities are most probably the polysaccharides available in the mushroom. Thus, usage of Reishi mushrooms as vegetables or as extract will be beneficial for the management of diabetes.Keywords: Antihyperglycemic, antidiabetic, insulin-sensitizer, anti-hyperlipidemic, Gano mushroom, Reishi mushroom, Ganoderma lucidum, alloxan-induced diabetes, Steroid induced diabetes, Glycated haemolgobin (HbA1c), Oral glucose tolerance test (OGTT), Hyperlipidemia

scholarly journals Central alarin ameliorated insulin resistance of adipocytes in type 2 diabetic rats

2014 ◽  
Vol 223 (3) ◽  
pp. 217-225 ◽  
Author(s):  
Lili Guo ◽  
Penghua Fang ◽  
Mei Yu ◽  
Mingyi Shi ◽  
Ping Bo ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Insulin Sensitivity ◽  
Plasma Membranes ◽  
Glucose Transporter ◽  
Diabetic Rats ◽  
The Body ◽  
Retinol Binding Protein ◽  
Mrna Levels ◽  
Type 2 Diabetic

Alarin, a regulatory peptide, belongs to the galanin family and plays the same regulatory roles as galanin in orexigenic activity and energy metabolism. Our previous studies had found that galanin might facilitate insulin sensitivity via activation of its central receptors. To date, little is known about whether central alarin may exert similar effects on insulin sensitivity. In order to investigate this, alarin and its specific antagonist, alarin 6–25Cys, were administered into the cerebral ventricles of type 2 diabetic rats (T2DR) to evaluate the changes in insulin resistance. The results indicated that central treatment with alarin significantly increased the body weight of animals, the 2-(N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)-2-deoxyglucose uptake, the plasma adiponectin levels, the glucose infusion rates in hyperinsulinemic–euglycemic clamp tests, the vesicle-associated membrane protein 2 as well as glucose transporter 4 (GLUT4 (SLC2A4)) protein and mRNA levels, and the ratios of GLUT4 contents in plasma membranes to total cell membranes in adipocytes, but reduced blood glucose and plasma retinol-binding protein 4 levels. These effects of alarin may be inhibited by pretreatment with alarin 6–25Cys. The above-mentioned results suggest that the central alarin projective system may facilitate insulin sensitivity and glucose uptake via the increase in GLUT4 content and GLUT4 translocation from intracellular pools to plasma membranes in T2DR.

scholarly journals SAT0111 THE RELATIONSHIP BETWEEN THE ADMINISTRATION OF IL-6 INHIBITORS AND INSULIN RESISTANCE IN PATIENTS WITH ACTIVE RHEUMATOID ARTHRITIS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 989.3-989
Author(s):  
A. Jitaru ◽  
C. Pomirleanu ◽  
M. M. Leon-Constantin ◽  
F. Mitu ◽  
C. Ancuta
Keyword(s):  
Rheumatoid Arthritis ◽  
Insulin Resistance ◽  
Insulin Sensitivity ◽  
Beneficial Effect ◽  
Disease Activity ◽  
Interleukin 6 ◽  
Normal Weight ◽  
Diabetic Patients ◽  
Model Assessment ◽  
Inflammatory Status

Background:Rheumatoid arthritis (RA) is associated with an increased cardiovascular (CV) risk, due not only to the traditional risk factors (hypertension, insulin resistance/diabetes, obesity, smoking), but to the inflammatory status as well. The blockade of interleukin-6 (IL-6) can regulate the glucose metabolism, reducing the glucose level and insulin resistance (IR). This beneficial effect is seen more in patients with normal values of body mass index (BMI), compared to the obese population.Objectives:Given the mentioned existing data, we aim to demonstrate the positive effect of IL-6 inhibitors in active RA patients with normal or increased BMI.Methods:We recruited 56 consecutive patients with definite and active RA, non-responders/partial responders to conventional synthetic Drug Modifying Anti-Rheumatic Drugs (csDMARDs)/biological therapy. For a period of 52 weeks, patients received subcutaneous Tocilizumab (TCZ) in a dose of 162mg once a week, according to European League Anti Rheumatism (EULAR) recommendation and National Protocol. We assessed demographics, RA-related parameters (clinical, inflammatory and immune) and metabolic markers, as well as the peripheral response to insulin, quantified by Homeostasis Model Assessment for insulin resistance (HOMA-IR) and the Quantitative Insulin Sensitivity Check Index (QUICKI). We did not include in the study the patients known with diabetes mellitus (DM) and those undergoing glucocorticoids.Results:After 52 weeks of treatment, most of the patients showed a statistically significant reduction of HOMA-IR (3.61 ± 1.21 at the onset vs. 2.45 ± 1.46 at the end of the study, p<0.001), while QUICKI registered a slight increase (0.32 ± 0.01 at the onset vs. 0.33 ± 0.01 at the end of the study, p<0.001). Also, the decrease in insulin and glucose levels were more obvious in patients with normal BMI, strictly related to disease activity.Conclusion:Long-term administration of TCZ in active RA is associated with a significant reduction of disease activity and IR, especially in normal weight patients. This confirms that obesity, as a CV risk factor, represents one of the main causes of IR.References:[1]Castañeda S, Remuzgo-Martínez S, López-Mejías R et al. Rapid beneficial effect of the IL-6 receptor blockade on insulin resistance and insulin sensitivity in non-diabetic patients with rheumatoid arthritis.Clin Exp Rheumatol. 2019; 37(3):465-473.[2]Lehrskov LL, Christensen RH. The role of interleukin-6 in glucose homeostasis and lipid metabolism.Semin Immunopathol. 2019; 41(4):491-499.[3]Ursini F, Russo E, Ruscitti P, Giacomelli R, De Sarro G. The effect of non-TNF-targeted biologics and small molecules on insulin resistance in inflammatory arthritis.Autoimmun Rev. 2018 Apr;17(4):399-404.Disclosure of Interests:Alexandra Jitaru: None declared, Cristina Pomirleanu: None declared, Maria-Magdalena Leon-Constantin: None declared, Florin Mitu: None declared, CODRINA ANCUTA Consultant of: AbbVie, Pfizer, Roche, Novartis, UCB, Ewopharma, Merck Sharpe and Dohme, and Eli Lilly, Speakers bureau: AbbVie, Pfizer, Roche, Novartis, UCB, Ewopharma, Merck Sharpe and Dohme, and Eli Lilly

scholarly journals Effect of carvedilol versus nebivolol on insulin resistance among non-diabetic, non-ischemic cardiomyopathy with heart failure

2020 ◽  
Vol 72 (1) ◽  
Author(s):  
Yasser Gaber Metwally ◽  
Heba Kamal Sedrak ◽  
Inass Fahiem Shaltout
Keyword(s):  
Heart Failure ◽  
Insulin Resistance ◽  
Insulin Sensitivity ◽  
Ischemic Cardiomyopathy ◽  
Diabetic Patients ◽  
Promising Strategy ◽  
Improve Insulin Resistance ◽  
First Choice ◽  
The Difference

Abstract Background Although B-blockers provide unequivocal benefits in heart failure (HF) management, some B-blockers worsen insulin resistance. It will be a promising strategy to recruit such a B blocker that did not worsen or can even improve insulin resistance (IR). So, this study aimed to assess the effect of two of the third-generation B-blockers (carvedilol versus nebivolol) on insulin sensitivity state in non-diabetic patients with non-ischemic cardiomyopathy with heart failure. Results Out of 43 patients enrolled, 58.1% represented the carvedilol group while 41.9% represented the nebivolol group. Nebivolol improves insulin resistance-related variables (fasting glucose, fasting insulin, and HOMA-IR; P < 0.001, 0.01, and 0.01 respectively). The percentage of change at homeostasis model of assessment (HOMA-IR), indicative of insulin sensitivity status, between baseline versus at 3-months follow-up level of intra-group comparison was increased by 4.58% in the carvedilol arm whereas it was decreased by 11.67% in the nebivolol arm, and the difference on the intragroup level of comparison was significant (P < 0.001 and 0.01 respectively). Conclusion Nebivolol improves insulin resistance-related variables .Nebivolol may be recommended as the B blocker of the first choice for those with non-ischemic cardiomyopathy heart failure with evident insulin resistance; however, larger scaled prospective multicenter randomized trials are needed for confirming our favorable results.

Berberine and Ginsenoside Rb1 Ameliorate Depression-Like Behavior in Diabetic Rats

2021 ◽  
pp. 1-19
Author(s):  
Jing-Hua Zhang ◽  
Hui-Zeng Yang ◽  
Hao Su ◽  
Jun Song ◽  
Yu Bai ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Glucose Metabolism ◽  
Plasma Cortisol ◽  
Adrenocorticotropic Hormone ◽  
Morphological Changes ◽  
Diabetic Rats ◽  
Diabetic Patients ◽  
Mild Stress ◽  
Ginsenoside Rb1 ◽  
Nissl Staining

Rhizoma coptidis(Huang-lian) and Asian ginseng have been widely used in the treatment of diabetes and other concurrent diseases with apparent effects. This study investigated the effects of the active ingredients of R. coptidis and ginseng, berberine and ginsenoside Rb1, on depression-like behavior in a rat diabetes model. The animal model was established via a high-fat diet and intraperitoneal injection of streptozotocin, while the animal’s depression-like behavior was induced via chronic unpredictable mild stress. These experimental rats were divided into four groups: control, depression-like behavior (DLB), metformin plus fluoxetine hydrochloride (M+FH), and berberine plus ginsenoside Rb1 (B+GRb1) groups. Glucose metabolism and insulin resistance were evaluated by oral glucose test and glucose clamp study. Depression-like behavior was evaluated via behavioral analyses, including forced swim, sucrose preference, elevated plus maze, and open-field tests. HE and Nissl staining, plasma cortisol expression of adrenocorticotropic hormone, and brain-derived neurotrophic factor (BDNF) levels were assayed to explore the mechanisms of action. Compared with the control, rats in the DLB group had a significant increase in the levels of blood glucose and depression-like behavior. The B+GRb1 group significantly improved glucose metabolism and insulin resistance, reduced depression-like behavior, downregulated levels of plasma cortisol and adrenocorticotropic hormone under stress, and upregulated BDNF protein expression compared to the DLB rats. HE and Nissl staining data revealed that B+GRb1 protected neurons from pathological and morphological changes. Thus, berberine and ginsenoside Rb1 not only improved glucose metabolism in diabetic rats but also ameliorated their depression-like behavior under chronic unpredictable stress. Mechanistically, studied data with plasma hormonal levels and brain neuronal pathological/morphological changes supported the observed effects. The combination of berberine and ginsenoside Rb1 may have a clinical value in the management of diabetic patients with depression.

scholarly journals Insulin sensitizers prevent fine particulate matter-induced vascular insulin resistance and changes in endothelial progenitor cell homeostasis

2016 ◽  
Vol 310 (11) ◽  
pp. H1423-H1438 ◽  
Author(s):  
Petra Haberzettl ◽  
James P. McCracken ◽  
Aruni Bhatnagar ◽  
Daniel J. Conklin
Keyword(s):  
Insulin Resistance ◽  
Bone Marrow ◽  
Particulate Matter ◽  
Insulin Sensitivity ◽  
Ambient Air ◽  
Air Pollutant ◽  
Ambient Air Pollution ◽  
Endothelial Progenitor ◽  
Insulin Sensitizer ◽  
Circulating Levels

Exposure to fine particular matter (PM2.5) increases the risk of developing cardiovascular disease and Type 2 diabetes. Because blood vessels are sensitive targets of air pollutant exposure, we examined the effects of concentrated ambient PM2.5 (CAP) on vascular insulin sensitivity and circulating levels of endothelial progenitor cells (EPCs), which reflect cardiovascular health. We found that CAP exposure for 9 days decreased insulin-stimulated Akt phosphorylation in the aorta of mice maintained on control diet. This change was accompanied by the induction of IL-1β and increases in the abundance of cleaved IL-18 and p10 subunit of Casp-1, consistent with the activation of the inflammasome pathway. CAP exposure also suppressed circulating levels of EPCs (Flk-1+/Sca-1+ cells), while enhancing the bone marrow abundance of these cells. Although similar changes in vascular insulin signaling and EPC levels were observed in mice fed high-fat diet, CAP exposure did not exacerbate diet-induced changes in vascular insulin resistance or EPC homeostasis. Treatment with an insulin sensitizer, metformin or rosiglitazone, prevented CAP-induced vascular insulin resistance and NF-κB and inflammasome activation and restored peripheral blood and bone marrow EPC levels. These findings suggest that PM2.5 exposure induces diet-independent vascular insulin resistance and inflammation and prevents EPC mobilization, and that this EPC mobilization defect could be mediated by vascular insulin resistance. Impaired vascular insulin sensitivity may be an important mechanism underlying PM2.5-induced vascular injury, and pharmacological sensitization to insulin action could potentially prevent deficits in vascular repair and mitigate vascular inflammation due to exposure to elevated levels of ambient air pollution. Listen to this article's corresponding podcast at http://ajpheart.podbean.com/e/particulate-matter-induced-vascular-insulin-resistance/ .

scholarly journals Susceptibility to oxidative stress, insulin resistance, and insulin secretory response in the development of diabetes from obesity

2007 ◽  
Vol 64 (6) ◽  
pp. 391-397 ◽  
Author(s):  
Radivoj Kocic ◽  
Dusica Pavlovic ◽  
Gordana Kocic ◽  
Milica Pesic
Keyword(s):  
Oxidative Stress ◽  
Insulin Resistance ◽  
Lipid Peroxidation ◽  
Insulin Sensitivity ◽  
Healthy Subjects ◽  
Critical Role ◽  
Secretory Response ◽  
Diabetic Patients ◽  
Apparent Difference ◽  
Insulin Secretory Response

Background/Aim. Oxidative stress plays a critical role in the pathogenesis of various diseases. Recent reports indicate that obesity may induce systemic oxidative stress. The aim of the study was to potentiate oxidative stress as a factor which may aggravate peripheral insulin sensitivity and insulinsecretory response in obesity in this way to potentiate development of diabetes. The aim of the study was also to establish whether insulin-secretory response after glucagonstimulated insulin secretion is susceptible to prooxidant/ antioxidant homeostasis status, as well as to determine the extent of these changes. Methods. A mathematical model of glucose/insulin interactions and C-peptide was used to indicate the degree of insulin resistance and to assess their possible relationship with altered antioxidant/prooxidant homeostasis. The study included 24 obese healthy and 16 obese newly diagnozed non-insulin dependent diabetic patients (NIDDM) as well as 20 control healthy subjects, matched in age. Results. Total plasma antioxidative capacity, erythrocyte and plasma reduced glutathione level were significantly decreased in obese diabetic patients, but also in obese healthy subjects, compared to the values in controls. The plasma lipid peroxidation products and protein carbonyl groups were significantly higher in obese diabetics, more than in obese healthy subjects, compared to the control healthy subjects. The increase of erythrocyte lipid peroxidation at basal state was shown to be more pronounced in obese daibetics, but the apparent difference was obtained in both the obese healthy subjects and obese diabetics, compared to the control values, after exposing of erythrocytes to oxidative stress induced by H2O2. Positive correlation was found between the malondialdehyde (MDA) level and index of insulin sensitivity (FIRI). Conclusion. Increased oxidative stress together with the decreased antioxidative defence seems to contribute to decreased insulin sensitivity and impaired insulin secretory response in obese diabetics, and may be hypothesized to favour the development of diabetes during obesity.

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