Whole body insulin resistance in rat offspring of mothers consuming alcohol during pregnancy or lactation: comparing prenatal and postnatal exposure

2004 ◽  
Vol 96 (1) ◽  
pp. 167-172 ◽  
Author(s):  
Li Chen ◽  
B. L. Grégoire Nyomba
Keyword(s):  
Insulin Resistance ◽  
Birth Weight ◽  
Glucose Tolerance ◽  
The Body ◽  
Whole Body ◽  
Glucose Disposal ◽  
Tolerance Index ◽  
Sensitivity Index ◽  
Intravenous Glucose ◽  
Rat Offspring

This study examined the effects of maternal ethanol (EtOH) consumption during pregnancy or lactation on glucose homeostasis in the adult rat offspring. Glucose disposal was determined by minimal model during an intravenous glucose tolerance test in rats that had a small or normal birth weight after EtOH exposure in utero and in rats whose mothers were given EtOH during lactation only. All three EtOH groups had decreased glucose tolerance index and insulin sensitivity index, but their glucose effectiveness was not different from that of controls. In addition, EtOH rat offspring that were small at birth had elevated plasma, liver, and muscle triglyceride levels. The data show that EtOH exposure during pregnancy programs the body to insulin resistance later in life, regardless of birth weight, but that this effect also results in dyslipidemia in growth-restricted rats. In addition, insulin resistance is also evident after EtOH exposure during lactation.

scholarly journals Polycystic Ovary Syndrome Is Associated with Tissue-Specific Differences in Insulin Resistance

2009 ◽  
Vol 94 (1) ◽  
pp. 157-163 ◽  
Author(s):  
Theodore P. Ciaraldi ◽  
Vanita Aroda ◽  
Sunder Mudaliar ◽  
R. Jeffrey Chang ◽  
Robert R. Henry
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Glucose Tolerance ◽  
Polycystic Ovary ◽  
Whole Body ◽  
Glucose Disposal ◽  
Signaling Proteins ◽  
Impaired Insulin ◽  
Isolated Adipocytes ◽  
Insulin Responsiveness

Abstract Objective: The potential differential contributions of skeletal muscle and adipose tissue to whole body insulin resistance were evaluated in subjects with polycystic ovary syndrome (PCOS). Research Design and Methods: Forty-two PCOS subjects and 15 body mass index-matched control subjects were studied. Insulin action was evaluated by the hyperinsulinemic/euglycemic clamp procedure. Isolated adipocytes and cultured muscle cells were analyzed for glucose transport activity; adipocytes, muscle tissue, and myotubes were analyzed for the expression and phosphorylation of insulin-signaling proteins. Results: Fifty-seven per cent of the PCOS subjects had impaired glucose tolerance and the lowest rate of maximal insulin-stimulated whole body glucose disposal compared to controls (P < 0.01). PCOS subjects with normal glucose tolerance had intermediate reduction in glucose disposal rate (P < 0.05 vs. both control and impaired glucose tolerance subjects). However, rates of maximal insulin-stimulated glucose transport (insulin responsiveness) into isolated adipocytes were comparable between all three groups, whereas PCOS subjects displayed impaired insulin sensitivity. In contrast, myotubes from PCOS subjects displayed reduced insulin responsiveness for glucose uptake and normal sensitivity. There were no differences between groups in the expression of glucose transporter 4 or insulin-signaling proteins or maximal insulin stimulation of phosphorylation of Akt in skeletal muscle, myotubes, or adipocytes. Conclusions: Individuals with PCOS display impaired insulin responsiveness in skeletal muscle and myotubes, whereas isolated adipocytes display impaired insulin sensitivity but normal responsiveness. Skeletal muscle and adipose tissue contribute differently to insulin resistance in PCOS. Insulin resistance in PCOS cannot be accounted for by differences in the expression of selected signaling molecules or maximal phosphorylation of Akt.

scholarly journals PSVIII-40 Late-Breaking Abstract: Variability in body composition is associated with insulin sensitivity in growing-finishing pigs

2020 ◽  
Vol 98 (Supplement_4) ◽  
pp. 350-351
Author(s):  
Hector H Salgado ◽  
Aline Remus ◽  
Marie-Pierre Letourneau-Montminy ◽  
Candido Pomar
Keyword(s):  
Insulin Resistance ◽  
Body Composition ◽  
Insulin Sensitivity ◽  
Growing Pigs ◽  
The Body ◽  
Whole Body ◽  
Oral Glucose ◽  
Sensitivity Index ◽  
Model Assessment ◽  
Glucose Ingestion

Abstract Growing pigs’ body composition variation can be associated with differences in insulin sensitivity given the insulin anabolic effect on protein and lipid synthesis. The objective of this study was to elucidate this association by relating the individual insulin response to the oral glucose tolerance test (OGTT) with the body composition of growing pigs. Thirty 95 kg jugular vein catheterized pigs received an oral dose of 1.75 g of glucose/kg of BW after 18 hours of fasting. Blood samples were collected at -20, -10, 5, 10, 15, 20, 25, 30, 45, 60, 90, 120, 150, 180, 210, 240, 300 and 360 min following glucose ingestion. Insulin sensitivity indexes were calculated and analyzed. Body lipids (LB, %) and protein (PB, %) composition were estimated by dual X-ray densitometry. Association between body composition and insulin sensitivity were studied by using partial least squares and correlations. Average LB and PB were 19.7% (CV = 7.6 %) and 16.2% (CV = 2.2%), respectively. Basal insulin blood concentration and area-under-the-curve (AUC) CV (51.9 % and 26.9 %, respectively) were larger than those for basal glucose and AUC (5.52 and 5.48 %, respectively). Additionally, insulin sensitivity (%S), steady-state beta cell function (%B), and insulin resistance (HOMA-IR) estimated with the Homeostasis Model Assessment (HOMA 2) and whole-body insulin sensitivity index (ISI) were highly variable between pigs which CV ranged from 30.1 % to 54.5 %. These results can indicate an early stage of insulin resistance in an important part of the studied pig population. LB and PB were affected by insulin sensitivity indexes (P < 0.05) which accounted, respectively, for 48% and 44% of the observed variation. In conclusion, lower insulin sensitivity was associated with higher body fat in growing pigs raised under similar conditions.

Effect of diet on insulin binding and glucose transport in rat sarcolemmal vesicles

1987 ◽  
Vol 252 (3) ◽  
pp. E420-E425
Author(s):  
G. K. Grimditch ◽  
R. J. Barnard ◽  
E. Sternlicht ◽  
R. H. Whitson ◽  
S. A. Kaplan
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Glucose Tolerance ◽  
Glucose Transport ◽  
Insulin Binding ◽  
Intravenous Glucose Tolerance Test ◽  
Whole Body ◽  
Intravenous Glucose ◽  
High Affinity ◽  
Sarcolemmal Vesicles

The purpose of this study was to compare the effects of a high-fat, high-sucrose diet (HFS) and a low-fat, high-complex carbohydrate diet (LFC) on glucose tolerance, insulin binding, and glucose transport in rat skeletal muscle. During the intravenous glucose tolerance test, peak glucose values at 5 min were significantly higher in the HFS group; 0-, 20-, and 60-min values were similar. Insulin values were significantly higher in the HFS group at all time points (except 60 min), indicating whole-body insulin resistance. Skeletal muscle was responsible, in part, for this insulin resistance, because specific D-glucose transport in isolated sarcolemmal (SL) vesicles under basal conditions was similar between LFC and HFS rats (35 +/- 5 vs. 32 +/- 4 pmol/mg protein), despite the higher plasma insulin levels. Scatchard analyses of insulin binding curves to sarcolemmal vesicles revealed that the Ka of the high-affinity binding sites was significantly reduced by the HFS diet (0.63 +/- 0.09 vs. 0.35 +/- 0.05 X 10(9) M-1); no other binding changes were noted. Specific D-glucose transport in SL vesicles after maximum insulin stimulation (1 U/kg) was significantly depressed in the HFS group (87 +/- 7 vs. 58 +/- 7 pmol/mg protein), indicating that HFS feeding also caused a postbinding defect. These results indicate that the insulin resistance in skeletal muscle associated with a HFS diet is due to both a decrease in the Ka of the high-affinity insulin receptors and a postbinding defect.

scholarly journals Lipoprotein Insulin Resistance Score: Validation and Utility in African Ancestry Populations

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A291-A292
Author(s):  
Vandhna Rani Sharma ◽  
Celeste K L Cravalho ◽  
Joshua Dawson ◽  
Alfredo Villalobos-Perez ◽  
Lilian Mabundo ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Glucose Tolerance ◽  
African Ancestry ◽  
European Ancestry ◽  
Whole Body ◽  
Cardiometabolic Disease ◽  
Screening Methods ◽  
Lower Sensitivity ◽  
Sensitivity Index ◽  
Abnormal Glucose Tolerance

Abstract Lipoprotein insulin resistance (LPIR) is an emerging biomarker of insulin resistance (IR), and a score of >48 is a strong predictor of incident cardiometabolic disease disease in a predominantly European ancestry population. LPIR is derived from a composite score of nuclear magnetic resonance (NMR) lipoprotein (Lp) parameters: triglyceride-rich (TRLp), low density (LDLp), and high density (HDLp). Yet, there is a paucity of data in African ancestry population, in whom there is low-normal TRLp despite high rates of IR and diabetes. Therefore, we examined Lp profiles and LPIR in a large African ancestry cohort, stratified by sex to determine the relationship of LPIR with established markers of IR. This is a secondary analysis from 2 studies (The Africans in America and Federal Women’s Study) designed to evaluate the genetic, biological and socio-environmental factors of diabetes risk in those of African ancestry. All participants self-identified as healthy and lived in the DC metro area, n= 518: 87.7% African immigrant,12.3% African American; age 39±10 (20-65y); BMI 28.1±4.8 (18.2–45.2 kg/m2); 58% male; 31% with obesity, and 37% with abnormal glucose tolerance; mean±SD (range); median (25th-75th percentile). Fasting measures of IR (LPIR, triglyceride/HDL (TG/HDL) ratio and homeostasis model of insulin resistance (HOMA-IR)) were compared with the whole-body insulin sensitivity index (WBISI) obtained during a multi-sample 75g OGTT, using spearman correlations. Lp particle size and subclass concentrations were measured by the amplitudes of the lipid-methyl group signals (NMR LipoProfile®). Men had lower BMI (27.1±3.9 vs 29.3±5.6 kg/m2), fat mass (23.5±5.5 vs 37.9±6.8 %), insulin resistance (WBISI: 6.2 (3.7–10.1) vs 4.9 (3.2–8.6), HOMA-IR: 1.3 (0.7–2.0) vs 1.6 (0.9–2.4), TG/HDL: 1.4 (1.0–2.2) vs 1.1 (0.8–1.5)), all P<0.001. LDLp (1226 (959–1531) vs 1239 (981–1553) nmol/L) and HDLp (17.6 (16.2–19) vs 17.5 (15.9–19.7) µmol/L) were similar by sex, P>0.6, while small LDLp 734 (523–1039) vs 541 (370–805) nmol/L and TRLp 80.5 (52.2–116.4) vs 53.6 (28.7 -89.3) nmol/L were higher in men. The total mean LPIR score was 28.9±18.7 and was higher in men (34±19 vs. 23±17), P<0.001. LPIR and TG/HDL ratio correlated with WBISI (r≥-0.40) and HOMA-IR (r≥0.40), P<0.001 with no differences by sex. HOMA-IR correlated with WBISI (r=-0.95, P<0.001). Overall, African ancestry individuals had high rates of abnormal glucose tolerance, obesity and LDLp but LPIR was 20 points lower than the established score for predicting cardiometabolic disease. It’s utility for detecting IR was modest but it may be an important adjunct for early cardiometabolic risk stratification in African ancestry populations in whom traditional screening methods have lower sensitivity.

Glucose tolerance and insulin action in healthy centenarians

1996 ◽  
Vol 270 (5) ◽  
pp. E890-E894 ◽  
Author(s):  
G. Paolisso ◽  
A. Gambardella ◽  
S. Ammendola ◽  
A. D'Amore ◽  
V. Balbi ◽  
...  
Keyword(s):  
Glucose Tolerance ◽  
Plasma Glucose ◽  
Insulin Action ◽  
Glucose Tolerance Test ◽  
Tolerance Test ◽  
Fat Free Mass ◽  
Whole Body ◽  
Glucose Disposal ◽  
Oral Glucose ◽  
Aged Subjects

Advancing age has been found to be associated with a decline in insulin action. Nevertheless, no study has been conducted in healthy centenarians. Our study investigates glucose tolerance and insulin action in centenarians. Fifty-two subjects were enrolled. The subjects were divided in three groups as follows: 1) adults (< 50 yr; n = 20);2) aged subjects (> 75 yr; n = 22); and 3) centenarians (> 100 yr; n = 14). Body composition was studied by bioimpedance analysis. In all subjects, an oral glucose tolerance test and euglycemic glucose clamp were performed. Centenarians have a lower fat-free mass (FFM) than aged subjects and adults, whereas fasting plasma glucose, triglycerides, free fatty acids, urea, and creatinine were not different in the groups studies. Centenarians had a 2-h plasma glucose concentration (6.0 +/- 0.2 mmol/l) that was lower than that in aged subjects (6.6 +/- 0.5 mmol/l, P < 0.05) but not different from adults [6.4 +/- 0.4 mmol/l, P = not significant (NS)]. During the clamp, plasma glucose and insulin concentrations were similar in the three groups. In these conditions, centenarians had a whole body glucose disposal (34.1 +/- 0.6 mumol.kg FFM-1.min 1) that was greater than that in aged subjects (23.3 +/- 0.5 mumol.kg FFM-1.min-1 P < 0.01) but not different from adults (34.6 +/- 0.5 mumol/kg x min, P = NS). In conclusion, our study demonstrates that centenarians compared with aged subjects had a preserved glucose tolerance and insulin action.

scholarly journals Treatment with an SSRI antidepressant restores hippocampo-hypothalamic corticosteroid feedback and reverses insulin resistance in low-birth-weight rats

2010 ◽  
Vol 298 (5) ◽  
pp. E920-E929 ◽  
Author(s):  
Esben S. Buhl ◽  
Thomas Korgaard Jensen ◽  
Niels Jessen ◽  
Betina Elfving ◽  
Christian S. Buhl ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Birth Weight ◽  
Insulin Sensitivity ◽  
Low Birth Weight ◽  
Mrna Expression ◽  
Hpa Axis ◽  
Whole Body ◽  
Oral Glucose ◽  
Red Muscle ◽  
Hpa Axis Activity

Low birth weight (LBW) is associated with type 2 diabetes and depression, which may be related to prenatal stress and insulin resistance as a result of chronic hypothalamic-pituitary-adrenal (HPA) axis hyperactivity. We examined whether treatment with a selective serotonin reuptake inhibitor [escitalopram (ESC)] could downregulate HPA axis activity and restore insulin sensitivity in LBW rats. After 4–5 wk of treatment, ESC-exposed LBW (SSRI-LBW) and saline-treated control and LBW rats (Cx and LBW) underwent an oral glucose tolerance test or a hyperinsulinemic euglycemic clamp to assess whole body insulin sensitivity. Hepatic phospho enolpyruvate carboxykinase (PEPCK) mRNA expression and red skeletal muscle PKB Ser473phosphorylation were used to assess tissue-specific insulin sensitivity. mRNA expression of the hypothalamic mineralocorticoid receptor was fivefold upregulated in LBW ( P < 0.05 vs. Cx), accompanied by increased corticosterone release during restraint stress and total 24-h urinary excretion ( P < 0.05 vs. Cx), whole body insulin resistance ( P < 0.001 vs. Cx), and impaired insulin suppression of hepatic PEPCK mRNA expression ( P < 0.05 vs. Cx). Additionally, there was a tendency for reduced red muscle PKB Ser473phosphorylation. The ESC treatment normalized corticosterone secretion ( P < 0.05 vs. LBW), whole body insulin sensitivity ( P < 0.01) as well as postprandial suppression of hepatic mRNA PEPCK expression ( P < 0.05), and red muscle PKB Ser473phosphorylation ( P < 0.01 vs. LBW). We conclude that these data suggest that the insulin resistance and chronic HPA axis hyperactivity in LBW rats can be reversed by treatment with an ESC, which downregulates HPA axis activity, lowers glucocorticoid exposure, and restores insulin sensitivity in LBW rats.

scholarly journals Novel Insights and Mechanisms of Lipotoxicity-Driven Insulin Resistance

2020 ◽  
Vol 21 (17) ◽  
pp. 6358 ◽  
Author(s):  
Benjamin Lair ◽  
Claire Laurens ◽  
Bram Van Den Bosch ◽  
Cedric Moro
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Acyl Chain ◽  
The Body ◽  
Glucose Disposal ◽  
Tissue Lipid ◽  
Lipid Species ◽  
Chain Composition

A large number of studies reported an association between elevated circulating and tissue lipid content and metabolic disorders in obesity, type 2 diabetes (T2D) and aging. This state of uncontrolled tissue lipid accumulation has been called lipotoxicity. It was later shown that excess lipid flux is mainly neutralized within lipid droplets as triglycerides, while several bioactive lipid species such as diacylglycerols (DAGs), ceramides and their derivatives have been mechanistically linked to the pathogenesis of insulin resistance (IR) by antagonizing insulin signaling and action in metabolic organs such as the liver and skeletal muscle. Skeletal muscle and the liver are the main sites of glucose disposal in the body and IR in these tissues plays a pivotal role in the development of T2D. In this review, we critically examine recent literature supporting a causal role of DAGs and ceramides in the development of IR. A particular emphasis is placed on transgenic mouse models with modulation of total DAG and ceramide pools, as well as on modulation of specific subspecies, in relation to insulin sensitivity. Collectively, although a wide number of studies converge towards the conclusion that both DAGs and ceramides cause IR in metabolic organs, there are still some uncertainties on their mechanisms of action. Recent studies reveal that subcellular localization and acyl chain composition are determinants in the biological activity of these lipotoxic lipids and should be further examined.

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