Compensatory alterations for insulin signal transduction and glucose transport in insulin-resistant diabetes

Bonini, James A.; Colca, Jerry R.; Dailey, Catherine; White, Morris F.; Hofmann, Cecilia

doi:10.1152/ajpendo.1995.269.4.e759

Cited by 28 publications

(22 citation statements)

References 2 publications

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“…Low IRS-1 expression has been observed to be associated with low GLUT-4 expression and a marked impairment in maximally insulin-stimulated glucose transport in adipocytes from nonobese subjects with a genetic predisposition for type 2 diabetes (Carvalho et al 2001). Changes in the expression of insulin signal transduction components, including PI3K, associated with altered glucose metabolism has also been described in the fat of obese insulin-resistant diabetic mice (Bonini et al 1995). In addition, depletion of GLUT-4 transporters and suppression of encoding mRNA were observed in adipocytes from obese subjects accompanied by a decrease in maximally stimulated glucose transport rate (Garvey et al 1991).…”

Section: Discussionmentioning

confidence: 99%

Low expression of insulin signaling molecules impairs glucose uptake in adipocytes after early overnutrition

Rodrigues¹,

Souza²,

Silva³

et al. 2007

Journal of Endocrinology

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Experimental and clinical studies have demonstrated that early postnatal overnutrition represents a risk factor for later obesity and associated metabolic and cardiovascular disturbance. In the present study, we assessed the levels of glucose transporter 4 (GLUT-4), GLUT-1, insulin receptor (IR), IR substrate 1 (IRS-1), phosphatidylinositol 3-kinase (PI3K) and Akt expression, as well as insulin-stimulated glucose transport and Akt activity in adipocytes from adult rats previously raised in small litters (SL). The normal litter (NL) served as control group. We also investigated glycemia, insulinemia, plasma lipid levels, and glucose tolerance. Our data demonstrated that early postnatal overfeeding induced a persistent hyperphagia accompanied by a significant increase in body weight until 90 days of age. The SL group also presented a significant increase (w42%) in epidydimal fat weight. Blood glucose, plasma insulin, and lipid levels were similar among the animals from the SL and NL groups. While insulin-stimulated glucose uptake was approximately twofold higher in adipocytes from the NL group, no stimulatory effect was observed in the SL group. The impaired insulin-stimulated glucose transport in adipose cells from the SL rats was associated with a significant decrease in GLUT-4, IRS-1 and PI3K expression, and Akt activity. In contrast, IR and Akt expression in adipocytes was not different between the SL and NL groups. Despite these alterations, our results showed no differences in glucose tolerance test in rats raised under different feeding conditions. Our findings reinforce a potent and long-term effect of neonatal overfeeding, which can program major changes in the metabolic regulatory mechanisms.

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Section: Discussionmentioning

confidence: 99%

Low expression of insulin signaling molecules impairs glucose uptake in adipocytes after early overnutrition

Rodrigues¹,

Souza²,

Silva³

et al. 2007

Journal of Endocrinology

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“…33 Expression of GRB2 protein in obese insulin-resistant diabetic KKAy mice was dramatically decreased compared to nondiabetic mice. 34 A third positional candidate is SSTR2, a G protein-coupled receptor, inhibits the action of gastrointestinal hormones, specifically gastrin and gastric acid, and reduces the rate of nutrient absorption. 35 Moreover, SSTR2 inhibits the release of insulin, glucagon, and growth hormone secretion.…”

Section: Discussionmentioning

confidence: 99%

Genetic mapping of a 17q chromosomal region linked to obesity phenotypes in the IRAS family study

et al. 2006

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Objective: Obesity is widely accepted to be influenced by both environmental and genetic factors. Several recent studies have used the positional cloning approach in an attempt to discover genes contributing to obesity. In the IRAS Family Study a genomewide scan was performed on 1425 individuals of Hispanic descent (90 extended pedigree families) to identify regions of the genome linked to obesity phenotypes. Methods: Nonparametric QTL linkage analysis was performed using a variance components approach. The genome scan was performed in two phases: an initial genome scan in 45 families and a replication scan in 45 families. Fine mapping and candidate gene analyses were also performed. General estimating equations (GEE1) and quantitative pedigree disequilibrium tests (QPDT) were used for association analysis of single SNP and haplotype data. Results: Evidence for linkage to obesity traits was observed in each scan on the long arm of chromosome 17. When data from both scans was combined, a region on chromosome 17q was identified with evidence of linkage to visceral adipose tissue (VAT; LOD 3.11), waist circumference (WAIST) (LOD 2.5) and body mass index (BMI) (LOD 2.81). Nine additional microsatellite markers were identified and genotyped on all Hispanic individuals, with a mean marker density of approximately 1 marker/3 cM. Evidence of linkage remained significant with LOD 3.05 for VAT, LOD 2.44 for BMI and LOD 1.92 for WAIST. Fine mapping analyses suggest the possibility of two different obesity loci. In addition, the LOD -1 interval of the major VAT peak decreased from 83-108 to 95-111 cM. Three positional candidate genes under the peak: somatostatin receptor 2 (SSTR2), galanin receptor 2 (GALR2), and growth hormone bound protein receptor 2 (GRB2) were chosen for detailed evaluation. Multiple polymorphisms within each candidate were genotyped and tested for association with the obesity phenotypes. Little evidence of association was detected between polymorphisms and obesity traits. Conclusion: In conclusion, replication of linkage and fine mapping suggest that a region on chromosome 17q contains a gene (or genes) that contributes to the genetic etiology of obesity with the strongest evidence for linkage to VAT. Candidate genes in the region do not appear to account for the evidence of linkage. Additional studies are necessary to identify the obesity-related polymorphisms.

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“…Although HMG-CoA reductase inhibitors are known to exert pleiotropic effects in inhibiting inflammation and enhancing restoration of endothelial function, the effects of statins on glucose metabolism and insulin resistance remain to be clarified. In the present study, we investigated the effects of atorvastatin on glucose metabolism and insulin resistance in KK/Ay mice, an animal model of insulin resistance and type 2 diabetes mellitus (15,16).…”

Section: Introductionmentioning

confidence: 99%

Effects of Atorvastatin on Glucose Metabolism and Insulin Resistance in KK/Ay Mice

Suzuki

Kakuta²,

Takahashi

et al. 2005

JAT

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Compensatory alterations for insulin signal transduction and glucose transport in insulin-resistant diabetes

Cited by 28 publications

References 2 publications

Low expression of insulin signaling molecules impairs glucose uptake in adipocytes after early overnutrition

Low expression of insulin signaling molecules impairs glucose uptake in adipocytes after early overnutrition

Genetic mapping of a 17q chromosomal region linked to obesity phenotypes in the IRAS family study

Effects of Atorvastatin on Glucose Metabolism and Insulin Resistance in KK/Ay Mice

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