scholarly journals Impaired Central Insulin Response in Aged Wistar Rats: Role of Adiposity

Endocrinology ◽  
2007 ◽  
Vol 148 (11) ◽  
pp. 5238-5247 ◽  
Author(s):  
Miriam García-San Frutos ◽  
Teresa Fernández-Agulló ◽  
Alain J. De Solís ◽  
Antonio Andrés ◽  
Carmen Arribas ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Signal Transduction ◽  
Body Weight ◽  
Food Intake ◽  
Insulin Receptor ◽  
Food Restriction ◽  
Wistar Rats ◽  
Insulin Response ◽  
Old Rats

Insulin, like leptin, is considered as a lipostatic signal acting at a central level. Aging and age-associated adiposity have been related to the development of leptin resistance in Wistar rats. In the present article, hypothalamic insulin response during aging has been studied in Wistar rats. Thus, the effects of intracerebroventricular infusion of insulin during a week on food intake and body weight as well as insulin signal transduction after acute intracerebroventricular insulin administration have been studied in 3-, 8-, and 24-month-old rats. To explore the possible role of age-associated adiposity, these experiments were also performed in 8- and 24-month-old rats after 3 months of food restriction to reduce visceral adiposity index to values below those of young animals. Intracerebroventricular administration of insulin during a week was more efficient at reducing food intake and body weight in 3-month-old rats than in 8- and 24-month-old rats. Hypothalamic insulin-stimulated insulin receptor, GSK3, AKT, and p70S6K phosphorylation decreased with aging. Insulin receptor and IRS-2 phosphoserine was increased in 24-month-old rats. Food restriction improved both insulin responsiveness and insulin signaling. These data suggest that Wistar rats develop hypothalamic insulin resistance with aging. This can be explained by alterations of the signal transduction pathway. The fact that food restriction improves central insulin response and signal transduction points to the age-associated adiposity as a key player in the development of central insulin resistance.

scholarly journals Effect of age and moderate food restriction on insulin sensitivity in Wistar rats: role of adiposity

2007 ◽  
Vol 194 (1) ◽  
pp. 131-141 ◽  
Author(s):  
Fernando Escrivá ◽  
M Lucía Gavete ◽  
Yasmín Fermín ◽  
Coralia Pérez ◽  
Nilda Gallardo ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Insulin Sensitivity ◽  
Calorie Restriction ◽  
Food Restriction ◽  
Glucose Utilization ◽  
Oral Glucose ◽  
Old Rats ◽  
Total Fat ◽  
Total Body

Insulin resistance develops with ageing in humans and rodents. Here, we have studied the evolution of insulin sensitivity with ageing trying to discriminate the role of adiposity from that of ageing in this process. We performed oral glucose tolerance tests and determined overall and tissue-specific glucose utilization under euglycemic-hyper-insulinemic conditions in 3-, 8-, and 24-month-old rats fed ad libitum, and in 8- and 24-month-old rats after 3 months of calorie restriction. Body composition and adipocyte-derived cytokines such as leptin, resistin, and adiponectin were analyzed. Overall insulin sensitivity decreases with ageing. Calorie restriction improves global insulin sensitivity in 8- but not in 24-month-old rats. Insulin-stimulated glucose utilization in adipose tissues decreases in 8 months, while in oxidative muscles it reaches significance only in older rats. Calorie restriction restores adipose tissue insulin sensitivity only in 8-month-old rats and no changes are observed in muscles of 24-month-old rats. Resistin and leptin increase with ageing. Food restriction lowers resistin and increases adiponectin in 8-month-old rats and decreases leptin in both ages. Visceral and total fat increase with ageing and decrease after calorie restriction. We conclude that accretion of visceral fat plays a key role in the development of insulin resistance after sexual maturity, which is reversible by calorie restriction. With aging, accumulation of retroperitoneal and total body fat leads to impaired muscle glucose uptake and to a state of insulin resistance that is difficult to reverse.

scholarly journals Role of neonatal hyperleptinaemia on serum adiponectin and suppressor of cytokine signalling-3 expression in young rats

2008 ◽  
Vol 101 (2) ◽  
pp. 250-256 ◽  
Author(s):  
Magna Cottini Fonseca Passos ◽  
Fabiane Pereira Toste ◽  
Sheila Cristina Potente Dutra ◽  
Paula Affonso Trotta ◽  
Fernanda Pereira Toste ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Body Weight ◽  
Food Intake ◽  
Leptin Receptor ◽  
Serum Insulin ◽  
Leptin Resistance ◽  
Serum Adiponectin ◽  
Lower Serum ◽  
Serum Adiponectin Concentration

Previously we had shown that neonatal leptin treatment programmes for both hyperleptinaemia and hyperinsulinaemia, which lead to leptin resistance and low expression of the hypothalamic leptin receptor (OB-Rb) of rats aged 150 d. Here we investigated in young post-weaned rats (age 30 d) if leptin treatment during lactation induces leptin and insulin resistance and if those changes are accompanied by changes in the suppressor of cytokine signalling-3 (SOCS-3) expression and serum adiponectin concentration. After delivery, the pups were divided into two groups: (1) a leptin group (Lep) that were injected with leptin daily (8 μg/100 g body weight subcutaneously) for the first 10 d of lactation; (2) a control (C) group, receiving saline. After weaning (day 21), body weight was monitored until the animals were age 30 d. They were tested for food intake in response to either leptin (0·5 mg/kg body weight intraperitoneally) (CL, LepL) or saline (CSal, LepSal) when they were aged 30 d. The CL group showed lower food intake, but no response was observed in the LepL group, suggesting leptin resistance. The Lep group had hyperleptinaemia (five-fold), hyperinsulinaemia (+42·5 %) and lower levels of serum adiponectin ( − 43·2 %). The hypothalamic expression of OB-Rb was lower ( − 22 %) and SOCS-3 was higher (+52·8 %) in the Lep group. We conclude that neonatal leptin treatment programmes for leptin resistance as soon as 30 d and suggests that SOCS-3 appears to be of particular importance in this event. In the Lep group, the lower serum adiponectin levels were accompanied by higher serum insulin, indicating a probable insulin resistance.

Insulin receptor mRNA splicing and altered metabolic control in aged and mildly insulin-deficient rats

1997 ◽  
Vol 272 (4) ◽  
pp. E607-E615
Author(s):  
M. M. Wiersma ◽  
D. Auboeuf ◽  
I. M. Nieuwenhuizen-Bakker ◽  
J. K. Radder ◽  
J. P. Riou ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Insulin Receptor ◽  
Insulin Response ◽  
Whole Body ◽  
Absolute Level ◽  
Peripheral Insulin Resistance ◽  
Tibialis Muscle ◽  
Old Rats ◽  
Exon 11

Using reverse transcription-competitive polymerase chain reaction, we measured the abundance of the mRNAs encoding the two spliced isoforms of insulin receptor in aged and mildly insulin-deficient rats. Twelve-month-old rats were characterized by peripheral insulin resistance and decreased glucose tolerance. Mild insulin deficiency, obtained by neonatal streptozotocin treatment, was associated with glucose intolerance due to reduced glucose-stimulated insulin response. Both models were associated with a decrease in the relative abundance of the mRNA with exon 11 in liver, heart, adipose tissue, and tibialis muscle, whereas a slight increase was seen in the extensor digitorum longus and no change in the soleus muscle. In the three muscles, the expression of the form without exon 11 largely predominated (>90%). In heart and adipose tissue, the two isoforms were expressed at a similar level in control rats. In both tissues, the form without exon 11 increased in streptozotocin-treated rats, whereas the absolute level of the form with exon 11 decreased in old rats. Although a decreased level of the variant with exon 11 correlated with insulin resistance of whole body glucose uptake, our results indicated that changes in the expression of the insulin receptor variants were secondary events and thus not the cause of the insulin resistance in old and mildly insulin-deficient rats.

Dose-dependent and time-dependent metabolic, hemodynamic, and redox disturbances in dexamethasone-treated Wistar rats

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Elvine P. Nguelefack-Mbuyo ◽  
Fernande P. Peyembouo ◽  
Christian K. Fofié ◽  
Télesphore B. Nguelefack
Keyword(s):  
Insulin Resistance ◽  
Body Weight ◽  
Catalase Activity ◽  
Wistar Rats ◽  
Chronic Treatment ◽  
Body Weight Loss ◽  
Redox Status ◽  
Duration Of Treatment ◽  
Renal Hypertrophy ◽  
Subchronic Treatment

Abstract Objectives Dexamethasone is used experimentally to induce insulin resistance and type 2 diabetes. However, data concerning the dose, the duration of treatment, and the associated comorbidities are inconsistent. The aim of this study was to compare the effects of different doses of dexamethasone and the duration of treatment necessary for the development of a model of insulin resistance that mimics the clinical condition with the associated comorbidities. Methods Dexamethasone was administered intramuscularly to male Wistar rats, at doses of 500 and 1,000 µg/kg/day for the subchronic treatment (eight consecutive days) and at doses of 5, 25, 50, and 100 µg/kg/day in chronic treatment (28 consecutive days). Effects on body weight, metabolism, hemodynamics, renal function, and redox status were evaluated. Results Both treatments induced a progressive body weight loss that was drastic in subchronic treatment, improved glucose tolerance without affecting fasting glycemia. Doses of 1,000 and 100 µg/kg were associated with hypertriglyceridemia, hypertension, and increased heart rate, cardiac and renal hypertrophy. Increased creatinemia associated with reduced creatinuria were observed in sub-chronic treatment while increased proteinuria and reduced creatinuria were noticed in chronic treatment. 1,000 µg/kg dexamethasone caused an increase in hepatic, and renal malondialdehyde (MDA) and glutathione (GSH) coupled with a reduction in catalase activity. The dose of 100 µg/kg induced a rise in GSH and catalase activity but reduced MDA levels in the kidney. Conclusions Doses of 1,000 µg/kg for subchronic and 100 µg/kg for chronic treatment exhibited similar effects and are the best doses to respective time frames to induce the model.

scholarly journals Role of Ventromedial Hypothalamus in Sucrose-Induced Obesity on Metabolic Parameters

2021 ◽  
pp. 097275312110057
Author(s):  
Archana Gaur ◽  
G.K. Pal ◽  
Pravati Pal
Keyword(s):  
Insulin Resistance ◽  
Weight Gain ◽  
Food Intake ◽  
Ventromedial Hypothalamus ◽  
Female Rats ◽  
Metabolic Parameters ◽  
Male Rats ◽  
Significant Weight Gain ◽  
The Metabolic Syndrome

Background: Obesity is because of excessive fat accumulation that affects health adversely in the form of various diseases such as diabetes, hypertension, cardiovascular diseases, and many other disorders. Our Indian diet is rich in carbohydrates, and hence the sucrose-induced obesity is an apt model to mimic this. Ventromedial hypothalamus (VMH) is linked to the regulation of food intake in animals as well as humans. Purpose: To understand the role of VMHin sucrose-induced obesity on metabolic parameters. Methods: A total of 24 adult rats were made obese by feeding them on a 32% sucrose solution for 10 weeks. The VMH nucleus was ablated in the experimental group and sham lesions were made in the control group. Food intake, body weight, and biochemical parameters were compared before and after the lesion. Results: Male rats had a significant weight gain along with hyperphagia, whereas female rats did not have a significant weight gain inspite of hyperphagia. Insulin resistance and dyslipidemia were seen in both the experimental and control groups. Conclusion: A sucrose diet produces obesity which is similar to the metabolic syndrome with insulin resistance and dyslipidemia, and a VMH lesion further exaggerates it. Males are more prone to this exaggeration.

The role of pulses in satiety, food intake and body weight management

2017 ◽  
Vol 38 ◽  
pp. 612-623 ◽  
Author(s):  
Sandra Clark ◽  
Alison M. Duncan
Keyword(s):  
Body Weight ◽  
Food Intake ◽  
Weight Management

scholarly journals The influence of food restriction versus ad libitum feeding of chow and purified diets on variation in body weight, growth and physiology of female Wistar rats

2012 ◽  
Vol 46 (2) ◽  
pp. 101-107 ◽  
Author(s):  
M Moraal ◽  
P P A M Leenaars ◽  
H Arnts ◽  
K Smeets ◽  
B S Savenije ◽  
...  
Keyword(s):  
Body Weight ◽  
Food Restriction ◽  
Wistar Rats ◽  
Statistical Significance ◽  
Blood Parameters ◽  
Calorie Intake ◽  
Restricted Feeding ◽  
Organ Weights ◽  
Female Wistar Rats ◽  
Ad Libitum

Ad libitum (AL) supply of standard chow is the feeding method most often used for rodents in animal experiments. However, AL feeding is known to result in a shorter lifespan and decreased health as compared with restricted feeding. Restricted feeding and thus limiting calorie intake prevents many health problems, increases lifespan and can also increase group uniformity. All this leads to a reduced number of animals needed. So-called standard chows are known to be prone to variation in composition. Synthetic foods have a more standard composition, contributing to group uniformity which, like diet reduction, may decrease the number of animals necessary to obtain statistical significance. In this study, we compared the effects of AL versus restricted feeding (25% reduction in food intake) on standard chow versus synthetic food of three different suppliers on body weight (BW), growth, several blood parameters and organ weights in growing female Wistar rats over a period of 61 days. Diet restriction led to a decreased growth and significantly reduced variation in BW and growth as compared with AL feeding. AL feeding on synthetic diets caused a significantly higher BW gain than on chow diets. Due to experimental design, this same effect occurred on food restriction. Blood parameters and organ weights were affected neither by diet type nor by amount. Incidentally, variations were significantly reduced on food restriction versus AL, and on synthetic diets versus chow diets. This study demonstrates that food restriction versus AL feeding leads to a significantly reduced variation in BW and growth, thereby indicating the potential for reduction when applying this feeding schedule.

Selective in vitro reversal of the insulin resistance of glucose transport in denervated rat skeletal muscle

1989 ◽  
Vol 257 (3) ◽  
pp. E418-E425 ◽  
Author(s):  
M. O. Sowell ◽  
S. L. Dutton ◽  
M. G. Buse
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Insulin Receptor ◽  
Glucose Transport ◽  
Glycogen Synthesis ◽  
Insulin Response ◽  
Medium Composition ◽  
Insulin Resistant ◽  
Denervated Muscles

Denervation (24 h) of skeletal muscle causes severe postreceptor insulin resistance of glucose transport and glycogen synthesis that is demonstrable in isolated muscles after short (30 min) preincubations. After longer preincubations (2-4 h), the insulin response of glucose transport increased to normal, whereas glycogen synthesis remained insulin resistant. Basal and insulin-stimulated amino acid transport were significantly lower in denervated muscles than in controls after short or long incubations, although the percentage stimulation of transport by insulin was not significantly different. The development of glucose transport insulin resistance after denervation was not attributable to increased sensitivity to glucocorticoids or adenosine. The selective in vitro reversal of glucose transport insulin resistance was not dependent on medium composition, did not require protein or prostaglandin synthesis, and could not be attributed to release of a positive regulator into the medium. The data suggest 1) the insulin receptor in muscle stimulates glucose transport by a signaling pathway that is not shared by other insulin-sensitive effector systems, and 2) denervation may affect insulin receptor signal transduction at more than one site.

Role of O-GlcNAcylation and endoplasmic reticulum stress on obesity and insulin resistance

2019 ◽  
Vol 44 (5) ◽  
pp. 599-610 ◽  
Author(s):  
Benan Pelin Sermikli ◽  
Gulizar Aydogdu ◽  
Afsar Abbasi Taghidizaj ◽  
Erkan Yilmaz
Keyword(s):  
Insulin Resistance ◽  
Endoplasmic Reticulum ◽  
Western Blot ◽  
Er Stress ◽  
Insulin Receptor ◽  
Serine Phosphorylation ◽  
Wild Type ◽  
Adipose Tissues ◽  
Insulin Resistant

Abstract Background Obesity is a global public health problem. Obesity closely associated with various metabolic diseases such as; insulin resistance, hypertension, dyslipidemia and cardiovascular diseases. Endoplasmic reticulum (ER) stress is a critical factor for insulin resistance. O-linked N-acetyl-glucosamine (O-GlcNAc); is the post-translational modification which is has a vital role in biological processes; including cell signaling, in response to nutrients, stress and other extracellular stimuli. Materials and methods In this study, we aimed to investigate the role of O-GlcNAc modification in the context of obesity and obesity-associated insulin resistance in adipose tissue. For this purpose, first, the visceral and epididymal adipose tissues of obese and insulin resistant C57BL/6 Lepob/Lepob and wild-type mice were used to determine the O-GlcNAc modification pattern by western blot. Secondly, the external stimulation of O-GlcNAc modification in wild-type mice achieved by intraperitoneal 5 mg/kg/day glucosamine injection every 24 h for 5 days. The effect of increased O-GlcNAc modification on insulin resistance and ER stress investigated in adipose tissues of glucosamine challenged wild-type mice through regulation of the insulin signaling pathway and unfolded protein response (UPR) elements by western blot. In addition to that, the O-GlcNAc status of the insulin receptor substrate-1 (IRS1) investigated in epididymal and visceral adipose tissues of ob/ob, wild-type and glucosamine challenged mice by immunoprecipitation. Results We found that reduced O-GlcNAc levels in visceral and epididymal adipose tissues of obese and insulin-resistant ob/ob mice, although interestingly we observed that increased O-GlcNAc modification in glucosamine challenged wild-type mice resulted in insulin resistance and ER stress. Furthermore, we demonstrated that the IRS1 was modified with O-GlcNAc in visceral and epididymal adipose tissues in both ob/ob mice and glucosamine-injected mice, and was compatible with the serine phosphorylation of this modification. Conclusion Our results suggest that O-GlcNAcylation of proteins is a crucial factor for intracellular trafficking regulates insulin receptor signaling and UPR depending on the cellular state of insulin resistance.

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