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insulin resistance/пролин

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A leucine-to-proline mutation in the insulin receptor in a family with insulin resistance.

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We have determined the primary structure of a mutant insulin receptor of a leprechaun patient born from a consanguineous marriage. A characteristic feature of leprechaunism is an extreme resistance to insulin. In this patient the insulin resistance seems to result from an observed lack of insulin

Selective Enhancement of Insulin Sensitivity in the Endothelium In Vivo Reveals a Novel Proatherosclerotic Signaling Loop.

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BACKGROUND In the endothelium, insulin stimulates endothelial NO synthase (eNOS) to generate the antiatherosclerotic signaling radical NO. Insulin-resistant type 2 diabetes mellitus is associated with reduced NO availability and accelerated atherosclerosis. The effect of enhancing endothelial

Over-expression of PRAS40 enhances insulin sensitivity in skeletal muscle.

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BACKGROUND Silencing proline-rich Akt substrate of 40-kDa (PRAS40) impairs insulin signalling in skeletal muscle. OBJECTIVE This study assessed the effects of over-expressing wild type or mutant AAA-PRAS40, in which the major phosphorylation sites and mTORC1-binding site were mutated, on insulin

Inactivation of SPAK kinase reduces body weight gain in mice fed a High-fat diet by improving energy expenditure and insulin sensitivity.

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The STE20/SPS1-related proline-alanine-rich protein kinase (SPAK) controls the activity of the electroneutral cation-chloride cotransporters (SLC12 family) and thus physiological processes such as modulation of cell volume, intracellular chloride concentration [Cl-]i, and transepithelial salt

A leucine to proline mutation at position 233 in the insulin receptor inhibits cleavage of the proreceptor and transport to the cell surface.

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We have previously shown that a homozygous mutation encoding a substitution of proline for leucine at position 233 in the insulin receptor is linked with the syndrome of leprechaunism, being a lethal form of insulin resistance in newborn children. Specific binding of insulin and insulin-stimulated

Proline-rich Akt substrate of 40-kDa contains a nuclear export signal.

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The proline-rich Akt substrate of 40-kDa (PRAS40) has been linked to the regulation of the activity of the mammalian target of rapamycin complex 1 as well as insulin action. Despite these cytosolic functions, PRAS40 was originally identified as nuclear phosphoprotein in Hela cells. This study aimed

The PPARgamma2 amino acid polymorphism Pro 12 Ala is prevalent in offspring of Type II diabetic patients and is associated to increased insulin sensitivity in a subgroup of obese subjects.

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OBJECTIVE Recently a mutation in the coding sequence of the adipocyte specific isoform peroxisome proliferator-activated receptor gamma2 (PPARgamma2) was described, leading to the substitution of Proline to Alanine at codon 12. Mutations in PPARgamma2 could have a role in people who are at increased

Metabolomics of Dynamic Changes in Insulin Resistance Before and After Exercise in PCOS.

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Background: Plasma elevated levels of branched chain amino acids (BCAA) and aromatic amino acids (AAA) have been associated with obesity and insulin resistance, but their relationship to stimulated insulin resistance (IR) in PCOS and in response to exercise is unknown. Indeed, it is unknown

The Pro12Ala PPARgamma2 gene missense mutation is associated with obesity and insulin resistance in Swedish middle-aged men.

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BACKGROUND A missense mutation in exon B of the adipocyte-specific isoform peroxisome proliferator-activated receptor-gamma2 (PPARgamma2) has recently been described, leading to the substitution of proline to alanine at codon 12, which causes a reduction in the transcriptional activity of

Role of PYK2 in the development of obesity and insulin resistance.

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Non-receptor proline-rich tyrosine kinase-2 (PYK2), which is activated by phosphorylation of one or more of its tyrosine residues, has been implicated in the regulation of GLUT4 glucose transporter translocation and glucose transport. Some data favor a positive role of PYK2 in stimulating glucose

Insulin resistance, ceramide accumulation and endoplasmic reticulum stress in experimental chronic alcohol-induced steatohepatitis.

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OBJECTIVE Chronic alcohol abuse causes steatohepatitis with insulin resistance, which impairs hepatocellular growth, survival and metabolism. However, growing evidence supports the concept that progressive alcohol-related liver injury may be mediated by concurrent mal-signaling through other

Proline-rich AKT substrate of 40-kDa (PRAS40) in the pathophysiology of cancer.

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Dysregulation of PI3K-AKT-mTOR pathway has been reported in various pathologies, such as cancer and insulin resistance. The proline-rich AKT substrate of 40-kDa (PRAS40), also known as AKT substrate 1 (AKT1S1), lies at the crossroads of these cascades and inhibits the activity of the mTOR complex 1

Chronic Exposure to Proline Causes Aminoacidotoxicity and Impaired Beta-Cell Function: Studies In Vitro.

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BACKGROUND Pancreatic islet-cell dysfunction is a hallmark in the development of diabetes, but the reasons for the primary β-cell defect are still elusive. Elevated circulating proline levels have been found in subjects with insulin resistance, obesity, and type 2 diabetes. Therefore, we assessed

Metabolic profiling of tissue-specific insulin resistance in human obesity: results from the Diogenes study and the Maastricht Study.

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Recent evidence indicates that insulin resistance (IR) in obesity may develop independently in different organs, representing different etiologies toward type 2 diabetes and other cardiometabolic diseases. The aim of this study was to investigate whether IR in the liver and IR in

Insulin resistance is associated with a metabolic profile of altered protein metabolism in Chinese and Asian-Indian men.

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OBJECTIVE Insulin resistance (IR) is associated with obesity, but can also develop in individuals with normal body weight. We employed comprehensive profiling methods to identify metabolic events associated with IR, while controlling for obesity. METHODS We selected 263 non-obese (BMI approximately
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