Cellular alterations in liver, skeletal muscle, and adipose tissue responsible for insulin resistance in obesity and type II diabetes

José, F.; Dohm, Lynis; Pories, Walter J.; Sinha, Madhur K.

doi:10.1002/dmr.5610050804

Cited by 163 publications

(89 citation statements)

References 73 publications

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“…We ascertained whether early and intermediate post-receptor signal events to glucose transport are altered in isolated adipocytes from obese women. We confirm earlier findings of a decrease in insulin sensitivity of glucose transport and reduced GLUT4 expression in isolated adipocytes from obese humans [3,24]. However, the maximal effect of insulin on glucose transport in isolated adipocytes was not different between lean and obese subjects.…”

Section: Discussionsupporting

confidence: 91%

“…Since many of the currently available insulin resistant and diabetic animal models arise from monogenetic lesions, molecular mechanisms leading to insulin resistance in humans are likely to be different. In obese humans, insulin resistance at the level of glucose transport is a characteristic defect in adipose tissue [3] and skeletal muscle [4,5,6]. Exercise and low calorie diet constitute the main components of therapeutic strategies to reduce obesity [7].…”

mentioning

confidence: 99%

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Insulin signal transduction and glucose transport in human adipocytes: effects of obesity and low calorie diet

et al. 2002

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Aim/hypothesis. We examined insulin signal transduction at the level of insulin receptor substrates (IRS) 1 and 2, phosphatidylinositol (PI) 3-kinase and glucose transport in isolated subcutaneous adipocytes from obese and lean women. Methods. Glucose transport and insulin signalling were investigated in isolated adipocytes from six obese women (BMI 36-43 kg/m 2 ) (before and after 11 days of very low calorie diet) and from six lean women (BMI 22-26 kg/m 2 ). Results. Insulin sensitivity of glucose transport was reduced in adipocytes from obese women (p<0.05), with further reductions in basal and maximal insulinstimulated glucose transport after a very low calorie diet (p<0.05). In obese women, IRS-1 associated PI 3-kinase activity was markedly impaired (p<0.05), whereas, IRS-2 associated PI 3-kinase activity was normal. IRS-1 associated PI 3-kinase activity remained blunted after a very low calorie diet, whereas IRS-2 associated PI 3-kinase activity was increased. GLUT4 protein was reduced by 37% in obese versus lean subjects (p<0.05), and decreased further after a very low calorie diet (from 19±4 to 14±4 arbitrary units; p<0.05). Conclusion/interpretation. IRS-1 signalling to PI 3-kinase is a site of insulin resistance in adipocytes from obese women, whereas insulin action on IRS-2 is normal. Thus, IRS-1 and IRS-2 undergo differential regulation in adipocytes from obese insulin resistant subjects. Finally, a very low calorie diet is associated with a further impairment in glucose transport in adipose tissue. The defect in glucose transport after a very low calorie diet occurs independent of further defects in insulin signalling at the level of the PI 3-kinase.

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Section: Discussionsupporting

confidence: 91%

mentioning

confidence: 99%

Insulin signal transduction and glucose transport in human adipocytes: effects of obesity and low calorie diet

et al. 2002

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“…Lipogenesis encompasses the processes of fatty acid synthesis and subsequent triglyceride synthesis and takes place in the liver and adipose tissues, while adipogenesis refers to the differentiation of preadipocytes into mature fat cells [16]. Inhibition of adipocyte differentiation presents a key strategy to control obesity since an increase in adipose mass is caused by both adipocyte hypertrophy and adipocyte hyperplasia [17]. In the present study, it had been found that M. citrifolia and herbs for weight loss (JL-TH, JL-RU, and CD-H) had anti-obesity activity related to adipogenesis in 3T3-L1 adipocytes.…”

Section: Lipid Accumulation Assaymentioning

confidence: 99%

Inhibition of Lipid Accumulation in 3t3-L1 Adipocytes by Morinda Citrifolia Linn. Leaf Extracts and Commercial Herbal Formulas for Weight Control

Saraphanchotiwitthaya

Sripalakit

2016

Int J Pharm Pharm Sci

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Objective: To determine the in vitro anti-obesity effects of Morinda citrifolia leaf extract and herbal formulas used for weight loss in Thailand on lipid accumulation in 3T3-L1 adipocytes.Methods: Differentiated 3T3-L1 adipocytes were treated with 0.1, 0.5 and 1 mg/ml M. citrifolia leaf extract, three herbal formulas (JL-RU, JL-TH, CD-H) and 1, 5 and 10 µg/ml rutin, gallic acid and caffeine. Lipid accumulation determined by measuring Oil Red O staining and triglyceride content measured by a colorimetric method in adipocytes were assayed compared to the control. The effect of test samples on the viability of preadipocytes and differentiated adipocytes were investigated.Results: Differentiated adipocytes treated with 1 mg/ml M. citrifolia extract moderately inhibited fat accumulation (45.12%) and highly reduced triglyceride content (85.09%). Among the three herbal formulas, JL-TH considerably inhibited fat accumulation (109.17%, 1 mg/ml) and decreased triglyceride content (95.00%, 1 mg/ml) in adipocytes; this was higher than that for CD-H and JL-RU, respectively. The viability of preadipocytes treated with CD-H at 1 mg/ml was slightly decreased while those treated with JL-TH at 0.05-1 mg/ml showed moderately decreased viability in a dose-response manner. For differentiated adipocytes, CD-H at 0.5-1 mg/ml moderately decreased cell viability while JL-TH at 0.05-1 mg/ml caused moderate to high reduction of cell viability in a dose-response relationship. Conclusion:M. citrifolia extract and three herbal formulas had anti-obesity effects in 3T3-L1 adipocytes, as indicated by a significant reduction in lipid accumulation, triglyceride content, and cell viability. These findings suggest a potential therapeutic approach for the prevention and treatment of obesity.

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“…The Ser/Thr phosphorylation of the receptor is of potential importance in the negative regulation of the IR tyrosine kinase activity that has been observed in the receptor from many non-insulin-dependent diabetic patients with insulin resistance [10]. It could also be involved in the desensitization of the receptor, either in response to insulin itself or through the activation of other signaling systems by various counter regulatory hormones such as tumor necrosis factor or glucagon [11][12][13].…”

Section: Introductionmentioning

confidence: 99%

Identification of serines‐1035/1037 in the kinase domain of the insulin receptor as protein kinase Cα mediated phosphorylation sites

Liu

Roth

1994

FEBS Letters

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A new site of serine phosphorylation (Ser-1035/1037) has been identified in the kinase domain of the insulin receptor. Mutant receptors missing these two serines were expressed in Chinese hamster ovary ceils overexpressing protein kinase C~t. These mutant receptors lacked a phorbol ester-stimulated phosphoserine containing tryptic peptide as demonstrated by both high percentage polyacrylamide/urea gel electrophoresis and two-dimensional tlc. Moreover, a synthetic peptide with the sequence of this tryptic peptide was phosphorylated by isolated protein kinase Cot and co-migrated with the phosphopeptide from in vivo labeled receptor. These results indicate that serine-1035 and/or 1037 in the kinase domain of the insulin receptor are phosphorylated in response to activation of protein kinase C~.

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Cellular alterations in liver, skeletal muscle, and adipose tissue responsible for insulin resistance in obesity and type II diabetes

Cited by 163 publications

References 73 publications

Insulin signal transduction and glucose transport in human adipocytes: effects of obesity and low calorie diet

Insulin signal transduction and glucose transport in human adipocytes: effects of obesity and low calorie diet

Inhibition of Lipid Accumulation in 3t3-L1 Adipocytes by Morinda Citrifolia Linn. Leaf Extracts and Commercial Herbal Formulas for Weight Control

Identification of serines‐1035/1037 in the kinase domain of the insulin receptor as protein kinase Cα mediated phosphorylation sites

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