Age-dependent onset of liver-specific IGF-I gene deficiency and its persistence in old age: implications for postnatal growth and insulin resistance in LID mice

2005 ◽  
Vol 289 (2) ◽  
pp. E288-E295 ◽  
Author(s):  
Zhengyi Tang ◽  
Rong Yu ◽  
Yarong Lu ◽  
A. F. Parlow ◽  
Jun-Li Liu
Keyword(s):  
Insulin Resistance ◽  
Insulin Sensitivity ◽  
Old Age ◽  
Pancreatic Islet ◽  
Postnatal Growth ◽  
Gene Deficiency ◽  
Igf I ◽  
Age Dependent ◽  
I Gene

To explore the limitations of the liver-specific IGF-I gene-deficient (LID) model and to further evaluate the role of endocrine IGF-I in early postnatal life and old age, we have studied these mice during the prepubertal period (from birth to 3 wk of age) and when they are 2 yr old. During the first 2 wk of life, IGF-I gene deficiency and the resulting reduction in serum IGF-I levels in LID mice did not reach sufficiently low levels when mice experience the most rapid and growth hormone (GH)-independent growth. It suggests that the role of liver-derived IGF-I in prepubertal, GH-independent postnatal growth cannot be established. From our previous studies, liver IGF-I mRNA level was abolished in adult LID mice, which causes elevated GH level, insulin resistance, pancreatic islet enlargement, and hyperinsulinemia. Interestingly in 2-yr-old LID mice, although liver IGF-I mRNA and serum IGF-I levels were still suppressed, serum insulin and GH levels had returned to normal. Compared with same-sex control littermates, aged male LID mice had significantly reduced body weight and fat mass and exhibited normal insulin sensitivity. On the other hand, aged female LID mice exhibited normal weight and marginal resistance to insulin actions. The pancreatic islet percentage (reflecting islet cell mass) was also restored to normal levels in aged LID mice. Thus, although the IGF-I gene deficiency is well maintained into old age, the insulin sensitivity, islet enlargement, and hyperinsulinemia that occurred in young adult mice have been mostly restored to normal levels, further supporting the age-dependent and sexual dimorphic features of the LID mice.

Role of nutrition in preventing insulin resistance in children

2016 ◽  
Vol 29 (3) ◽  
Author(s):  
Annalisa Blasetti ◽  
Simone Franchini ◽  
Laura Comegna ◽  
Giovanni Prezioso ◽  
Francesco Chiarelli
Keyword(s):  
Insulin Resistance ◽  
Insulin Sensitivity ◽  
Fetal Development ◽  
Maternal Nutrition ◽  
Dietary Habits ◽  
Prenatal Period ◽  
Dietary Carbohydrates ◽  
Macro And Micronutrients

AbstractNutrition during prenatal, early postnatal and pubertal period is crucial for the development of insulin resistance and its consequences. During prenatal period fetal environment and nutrition seems to interfere with metabolism programming later in life. The type of dietary carbohydrates, glycemic index, protein, fat and micronutrient content in maternal nutrition could influence insulin sensitivity in the newborn. The effects of lactation on metabolism and nutritional behavior later in life have been studied. Dietary habits and quality of diet during puberty could prevent the onset of a pathological insulin resistance through an adequate distribution of macro- and micronutrients, a diet rich in fibers and vegetables and poor in saturated fats, proteins and sugars. We want to overview the latest evidences on the risk of insulin resistance later in life due to both nutritional behaviors and components during the aforementioned periods of life, following a chronological outline from fetal development to adolescence.

scholarly journals Relationship between the indexes of insulin resistance and metabolic status in dairy cows during early lactation

2017 ◽  
Vol 67 (1) ◽  
pp. 57-70 ◽  
Author(s):  
Marko Cincović ◽  
Danijela Kirovski ◽  
Ivan Vujanac ◽  
Branislava Belić ◽  
Radojica Djoković
Keyword(s):  
Insulin Resistance ◽  
Insulin Sensitivity ◽  
Body Condition ◽  
Negative Correlation ◽  
Body Condition Score ◽  
Metabolic Status ◽  
Early Lactation ◽  
Igf I ◽  
Condition Score ◽  
Linear Correlations

AbstractInsulin resistance is a phenomenon which accompanies the ongoing metabolic adaptation in cows during early lactation. The aim of our study was to determine the linear correlations of HOMA (Homeostatic Model Assessment), QUICKI (Quantitative Insulin Sensitivity Check Index) and RQUICKI (Revised Quantitative Insulin Sensitivity Check Index) indexes of insulin resistance with the metabolic status of cows (concentration of hormones, metabolites and body condition score). The experiment included 40 Holstein-Frisian cows in the first week after calving. Indexes of insulin resistance valued: 18.68±5.43 (HOMA), 0.39±0.06 (QUICKI) and 0.45±0.06 (RQUICKI). Linear correlations were examined by testing the coefficient of correlation (r), determination (r2,%) and regression parameter beta (b) in linear equation. A negative correlation was found between HOMA and IGF-I (insulin growth factor I) (r=−0.51, r2=25.0, b=−1.1257, p<0.01). HOMA showed a positive correlation with BHB (betahidroxybutyrate) (r=0.48, r2=23.2, b=0.0234, p<0.01). A positive correlation was found between QUICKI and IGF-I (r=0.30, r2=10.0 b=46.7900, p<0.05) and cholesterol (r=0.44, r2=18.3, b=1.9021, p<0.01). In contrast, QUICKI and BHB (r=0.51, r2=27.1, b=−1.7241, p<0.01), just like QUICKI and BCS (r=0.46, r2=20.9, b=−2.424, p<0.01), showed a negative correlation. RQUICKI showed positive correlations with IGF-I (r=0.48, r2=22.8, b=28.1230, p<0.01), T4 (r=0.47, r2=22.1, b=87.142, p<0.01) and triglycerides (r=0.36, r2=13, b=0.0407, p<0.05) but negative correlations with cortisol (r=−0.36, r2=13.0, b=−9.0332, p<0.05), STH (somatotropic hormone) (r=−0.42, r2=17.3, b=−5.4976, p<0.01), BHB (r=−0.62, r2=38.3, b=−1.1872, p<0.01), total bilirubin (r=−0.58, r2=33.7, b=−7.131, p<0.01) and BCS (body condition score) (r=−0.6, r2=36.4, b=−1.8347, p<0.01). In conclusion, indexes of insulin resistance may be used to evaluate the metabolic status of cows in early lactation. RQUICKI might be the most appropriate predictor of metabolic status due to its linear relationship with most of the parameters included in homeorhetic process.

scholarly journals Duration of rise in free fatty acids determines salicylate's effect on hepatic insulin sensitivity

2013 ◽  
Vol 217 (1) ◽  
pp. 31-43 ◽  
Author(s):  
Sandra Pereira ◽  
Wen Qin Yu ◽  
María E Frigolet ◽  
Jacqueline L Beaudry ◽  
Yaniv Shpilberg ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Insulin Sensitivity ◽  
Muscle Protein ◽  
Hepatic Insulin Resistance ◽  
Skeletal Muscle Protein ◽  
Protein Levels ◽  
Peripheral Insulin Resistance ◽  
Plasma Ffa ◽  
A Site

We have shown in rats that sodium salicylate (SS), which inhibits IkBa kinase B (IKKB), prevents hepatic and peripheral insulin resistance caused by short-term (7 h) i.v. administration of Intralipid and heparin (IH). We wished to further determine whether this beneficial effect of SS persisted after prolonged (48 h) IH infusion, which better mimics the chronic free fatty acid (FFA) elevation of obesity. Hence, we performed hyperinsulinemic euglycemic clamps with tritiated glucose methodology to determine hepatic and peripheral insulin sensitivity in rats infused with saline, IH, IH and SS, or SS alone. SS prevented peripheral insulin resistance (P<0.05) caused by prolonged plasma FFA elevation; however, it did not prevent hepatic insulin resistance. In skeletal muscle, protein levels of phospho-IkBa were augmented by prolonged IH administration and this was prevented by SS, suggesting that IH activates while SS prevents the activation of IKKB. Markers of IKKB activation, namely protein levels of phospho-IkBa and IkBa, indicated that IKKB is not activated in the liver after prolonged FFA elevation. Phosphorylation of serine 307 at insulin receptor substrate (IRS)-1, which is a marker of proximal insulin resistance, was not altered by IH administration in the liver, suggesting that this is not a site of hepatic insulin resistance in the prolonged lipid infusion model. Our results suggest that the role of IKKB in fat-induced insulin resistance is time and tissue dependent and that hepatic insulin resistance induced by prolonged lipid elevation is not due to an IRS-1 serine 307 kinase.

Impact of PPAR-α induction on glucose homoeostasis in alcohol-fed mice

2013 ◽  
Vol 125 (11) ◽  
pp. 501-511 ◽  
Author(s):  
Valérie Lebrun ◽  
Olivier Molendi-Coste ◽  
Nicolas Lanthier ◽  
Christine Sempoux ◽  
Patrice D. Cani ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Liver Disease ◽  
Insulin Sensitivity ◽  
Alcohol Consumption ◽  
Insulin Signalling ◽  
Liver Steatosis ◽  
Hepatic Insulin Resistance ◽  
Alcoholic Fatty Liver ◽  
Glucose Homoeostasis

Alcohol consumption is a major cause of liver disease. It also associates with increased cardiovascular risk and Type 2 diabetes. ALD (alcoholic liver disease) and NAFLD (non-alcoholic fatty liver disease) share pathological features, pathogenic mechanisms and pattern of disease progression. In NAFLD, steatosis, lipotoxicity and liver inflammation participate to hepatic insulin resistance. The aim of the present study was to verify the effect of alcohol on hepatic insulin sensitivity and to evaluate the role of alcohol-induced steatosis and inflammation on glucose homoeostasis. C57BL/6J mice were fed for 20 days a modified Lieber–DeCarli diet in which the alcohol concentration was gradually increased up to 35% of daily caloric intake. OH (alcohol liquid diet)-fed mice had liver steatosis and inflammatory infiltration. In addition, these mice developed insulin resistance in the liver, but not in muscles, as demonstrated by euglycaemic–hyperinsulinaemic clamp and analysis of the insulin signalling cascade. Treatment with the PPAR-α (peroxisome-proliferator-activated receptor-α) agonist Wy14,643 protected against OH-induced steatosis and KC (Kupffer cell) activation and almost abolished OH-induced insulin resistance. As KC activation may modulate insulin sensitivity, we repeated the clamp studies in mice depleted in KC to decipher the role of macrophages. Depletion of KC using liposomes-encapsuled clodronate in OH-fed mice failed both to improve hepatic steatosis and to restore insulin sensitivity as assessed by clamp. Our study shows that chronic alcohol consumption induces steatosis, KC activation and hepatic insulin resistance in mice. PPAR-α agonist treatment that prevents steatosis and dampens hepatic inflammation also prevents alcohol-induced hepatic insulin resistance. However, KC depletion has little impact on OH-induced metabolic disturbances.

scholarly journals Prevalence and Clinical Characteristics of Children and Adolescents with Metabolically Healthy Obesity: Role of Insulin Sensitivity

Life ◽  
2020 ◽  
Vol 10 (8) ◽  
pp. 127 ◽  
Author(s):  
Federica Vinciguerra ◽  
Andrea Tumminia ◽  
Roberto Baratta ◽  
Alfredo Ferro ◽  
Salvatore Alaimo ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Insulin Sensitivity ◽  
Children And Adolescents ◽  
Metabolic Phenotype ◽  
Sensitivity Index ◽  
Insulinogenic Index ◽  
Model Assessment ◽  
Insulin Resistant ◽  
Metabolically Healthy

Obesity represents a major risk factor for metabolic disorders, but some individuals, “metabolically healthy” (MHO), show less clinical evidence of these complications, in contrast to “metabolically unhealthy” (MUO) individuals. The aim of this cross-sectional study is to assess the prevalence of the MHO phenotype in a cohort of 246 overweight/obese Italian children and adolescents, and to evaluate their characteristics and the role of insulin resistance. Homeostasis model assessment–insulin resistance (HOMA-IR), insulin sensitivity index (ISI), insulinogenic index (IGI) and disposition index (DI) were all calculated from the Oral Glucose Tolerance Test (OGTT). MHO was defined by either: (1) HOMA-IR < 2.5 (MHO-IRes), or (2) absence of the criteria for metabolic syndrome (MHO-MetS). The MHO prevalence, according to MHO-MetS or MHO-IRes criteria, was 37.4% and 15.8%, respectively. ISI was the strongest predictor of the MHO phenotype, independently associated with both MHO-IRes and MHO-MetS. The MHO-MetS group was further subdivided into insulin sensitive or insulin resistant on the basis of HOMA-IR (either < or ≥ 2.5). Insulin sensitive MHO-MetS patients had a better metabolic profile compared to both insulin resistant MHO-MetS and MUO-MetS individuals. These data underscore the relevance of insulin sensitivity to identifying, among young individuals with overweight/obesity, the ones who have a more favorable metabolic phenotype.

scholarly journals Adipocyte PU.1 knockout promotes insulin sensitivity in HFD-fed obese mice

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Denise E. Lackey ◽  
Felipe C. G. Reis ◽  
Roi Isaac ◽  
Rizaldy C. Zapata ◽  
Dalila El Ouarrat ◽  
...  
Keyword(s):  
Gene Expression ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Insulin Sensitivity ◽  
Glucose Tolerance ◽  
Target Genes ◽  
Obese Mice ◽  
Tissue Macrophage

Abstract Insulin resistance is a key feature of obesity and type 2 diabetes. PU.1 is a master transcription factor predominantly expressed in macrophages but after HFD feeding PU.1 expression is also significantly increased in adipocytes. We generated adipocyte specific PU.1 knockout mice using adiponectin cre to investigate the role of PU.1 in adipocyte biology, insulin and glucose homeostasis. In HFD-fed obese mice systemic glucose tolerance and insulin sensitivity were improved in PU.1 AKO mice and clamp studies indicated improvements in both adipose and liver insulin sensitivity. At the level of adipose tissue, macrophage infiltration and inflammation was decreased and glucose uptake was increased in PU.1 AKO mice compared with controls. While PU.1 deletion in adipocytes did not affect the gene expression of PPARg itself, we observed increased expression of PPARg target genes in eWAT from HFD fed PU.1 AKO mice compared with controls. Furthermore, we observed decreased phosphorylation at serine 273 in PU.1 AKO mice compared with fl/fl controls, indicating that PPARg is more active when PU.1 expression is reduced in adipocytes. Therefore, in obesity the increased expression of PU.1 in adipocytes modifies the adipocyte PPARg cistrome resulting in impaired glucose tolerance and insulin sensitivity.

159 EFFECTS OF EMBRYO TRANSFER IN A LARGER BREED ON POSTNATAL GROWTH AND GLUCOSE METABOLISM IN HORSES

2013 ◽  
Vol 25 (1) ◽  
pp. 228
Author(s):  
P. Peugnet ◽  
A. Tarrade ◽  
C. Sandersen ◽  
M. Dahirel ◽  
D. Guillaume ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Insulin Sensitivity ◽  
Embryo Transfer ◽  
Fetal Growth ◽  
Fasting Glucose ◽  
Plasma Concentrations ◽  
Postnatal Growth ◽  
Glucose Regulation ◽  
Intravenous Glucose ◽  
Glucose Clearance

In equids, the size of the uterus determines fetal intrauterine development, which in turn affects postnatal insulin sensitivity and growth rate. We induced intrauterine growth enhancement through embryo transfer using Pony (P), Saddlebred (S), and Draft (D) horses and studied growth and insulin sensitivity in foals from birth to one year of age. Control pregnancies of S-in-S (n = 14) and P-in-P (n = 10) were obtained by AI. Enhanced fetal growth was obtained by transferring S (S-in-D, n = 7) and P embryos (P-in-D, n = 5) into D mares. From birth to weaning (180 days), each foal was kept with its surrogate P, S, or D dam. At 3, 140, and 380 days, glucose clearance and pancreatic beta cell response to exogenous glucose were assessed with an intravenous glucose tolerance test (IVGTT). At 200 days, the euglycemic-hyperinsulinemic clamp method was used to determine the sensitivity and responsiveness of tissues to exogenous insulin. Plasma T3, T4, and IGF1 were assayed at 3 and 180 days. Data were analysed using one-way ANOVA and Tukey post hoc tests. S-in-S were heavier and taller than P-in-P from birth to 380 days (P < 0.001). Before weaning, plasma concentrations of several hormones involved in growth were lower in S-in-S than P-in-P (at 3 and 180 days, respectively, T3: P = 0.08 and P = 0.02, T4: P < 0.001 and P = 0.06, IGF1: P = 0.04 and P < 0.001). No difference was found in glucose regulation between these groups. In contrast, post-weaning insulin resistance was observed in P-in-P at 200 days (P < 0.001) and confirmed at 380 days where they exhibited slower glucose clearance (P = 0.03) associated with higher fasting glucose (P < 0.001) than S-in-S. Fetal growth was not enhanced in S-in-D with no difference in height and weight at birth. Although S-in-D grew faster from 30 to 140 days, growth rates were not different from S-in-S after weaning, weaning coinciding with lower T3 (P < 0.001) in S-in-D than in S-in-S. Glucose regulation was not different between the two groups, but insulin remains to be assayed at 140 and 380 days. Fetal growth was enhanced in P-in-D: at birth, they were heavier (P = 0.01) and taller (P < 0.001) than P-in-P. Growth of P-in-D was faster until weaning. No more difference, however, was observed between P-in-D and P-in-P at 380 days. Plasma concentrations of T3 (P = 0.03) and those of T4 (P < 0.001) were lower at 3 days and T3 was still lower at 180 days (P < 0.001) in P-in-D compared with P-in-P. Moreover, P-in-D developed early insulin resistance: insulin secretion was higher in P-in-D compared with P-in-P (P = 0.002) after IVGTT at 3 days. At 200 days, however, P-in-D and P-in-P had the same sensitivity to insulin. There was no difference in glucose clearance rates at 380 days, but P-in-D had lower fasting glucose (P < 0.001) than P-in-P. Insulin assays at 140 and 380 days are pending. In conclusion, these data indicate that transfer of a small breed embryo into a large breed mare and subsequent suckling by the recipient mare can enhance fetal and postnatal growth and affect the foal’s glycaemia and sensitivity to insulin at birth and in subsequent months. Ongoing work includes analyses of milk samples and effects on general health.

scholarly journals Role of Cannabinoid Receptor Type 1 in Insulin Resistance and Its Biological Implications

2019 ◽  
Vol 20 (9) ◽  
pp. 2109 ◽  
Author(s):  
Arulkumar Nagappan ◽  
Jooyeon Shin ◽  
Myeong Ho Jung
Keyword(s):  
Insulin Resistance ◽  
Body Weight ◽  
Insulin Sensitivity ◽  
Hepatic Steatosis ◽  
Cannabinoid Receptor ◽  
Inflammatory Responses ◽  
Hepatic Insulin Resistance ◽  
Leptin Resistance ◽  
Peripheral Tissues

Endogenous cannabinoids (ECs) are lipid-signaling molecules that specifically bind to cannabinoid receptor types 1 and 2 (CB1R and CB2R) and are highly expressed in central and many peripheral tissues under pathological conditions. Activation of hepatic CB1R is associated with obesity, insulin resistance, and impaired metabolic function, owing to increased energy intake and storage, impaired glucose and lipid metabolism, and enhanced oxidative stress and inflammatory responses. Additionally, blocking peripheral CB1R improves insulin sensitivity and glucose metabolism and also reduces hepatic steatosis and body weight in obese mice. Thus, targeting EC receptors, especially CB1R, may provide a potential therapeutic strategy against obesity and insulin resistance. There are many CB1R antagonists, including inverse agonists and natural compounds that target CB1R and can reduce body weight, adiposity, and hepatic steatosis, and those that improve insulin sensitivity and reverse leptin resistance. Recently, the use of CB1R antagonists was suspended due to adverse central effects, and this caused a major setback in the development of CB1R antagonists. Recent studies, however, have focused on development of antagonists lacking adverse effects. In this review, we detail the important role of CB1R in hepatic insulin resistance and the possible underlying mechanisms, and the therapeutic potential of CB1R targeting is also discussed.

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