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  • obesity
  • Huang X, Liu G, Guo J, Su Z. The PI3K/AKT pathway in obesity and type 2 diabetes. (ijbs.com)
  • Obesity and type 2 diabetes mellitus are complicated metabolic diseases that affect multiple organs and are characterized by hyperglycaemia. (ijbs.com)
  • Currently, stable and effective treatments for obesity and type 2 diabetes mellitus are not available. (ijbs.com)
  • Based on accumulated evidences, the PI3K/AKT signalling pathway is required for normal metabolism due to its characteristics, and its imbalance leads to the development of obesity and type 2 diabetes mellitus. (ijbs.com)
  • We also summarize evidences for recently identified therapeutic targets of the PI3K/AKT pathway as treatments for obesity and type 2 diabetes mellitus. (ijbs.com)
  • The prevalence of obesity has grown at an alarming rate although specific public health policies and treatment efforts have been developed to resist the obesity epidemic [ 1 ], potentially leading to increased numbers of patients affected by complications of obesity, such as the most devastating type 2 diabetes mellitus (T2DM) [ 2 ]. (ijbs.com)
  • WHO defines normal weight, overweight, and obesity as a body mass index (BMI, calculated as ratio of weight in kg/height in m 2 ) of 18.5-24.9, 25-29.9, and 30 or greater, respectively. (hindawi.com)
  • As in humans, obesity during pregnancy in mice results in elevated maternal insulin levels and metabolic programming of offspring. (physiology.org)
  • Obesity is characterized by a body mass index (BMI) of over 30 kg/m 2 . (hindawi.com)
  • Furthermore, midlife overweight and obesity might increase the risk for dementia during aging [ 2 - 4 ]. (hindawi.com)
  • It seems to be difficult to estimate the exact role of obesity itself for the initiation or progress of cognitive impairment. (hindawi.com)
  • Furthermore, obesity is associated with a variety of cardiovascular risk factors influencing long-term cognitive performance. (hindawi.com)
  • Moreover, lower cognitive abilities are a risk factor for obesity, but on the other hand, dementia in later life might be associated with lower BMI. (hindawi.com)
  • Thus, it might well be that obesity in younger or midlife is a risk factor for dementia, and dementia is causing weight loss and cachexia on the long run. (hindawi.com)
  • However, there is growing evidence that disturbed metabolic signals in obesity or type 2 diabetes feedback to the central nervous system (CNS) influencing brain function and possibly the pathogenesis of dementia or cognitive decline. (hindawi.com)
  • Recently, insulin and insulin-like growth factors (IGFs) have been suggested as important modifiers for the pathogenesis of neurodegenerative diseases, providing a link between obesity, type 2 diabetes (T2D), and cognitive impairment or even the pathogenesis of Alzheimer's disease. (hindawi.com)
  • Obesity is a well-known risk factor for the development of T2DM. (springer.com)
  • PI3K
  • PI3K/AKT signalling plays a central role in cellular physiology by mediating growth factor signals during organismal growth and critical cellular processes, such as glucose homeostasis, lipid metabolism, protein synthesis and cell proliferationand survival[ 9 ]. (ijbs.com)
  • Growth factors such as insulin and IGF-1 can also induce PI3K activation independently of leucine. (anabolicminds.com)
  • S2 cell size, protein synthesis, and glucose import were largely insensitive to manipulations of insulin signaling components, suggesting that cellular energy levels and TOR activity can be maintained through insulin/PI3K-independent mechanisms in S2 cell culture. (biomedcentral.com)
  • gene
  • Comprehensive studies on gene expression, therefore, will need to include posttranscriptional events such as mRNA translation, posttranslational modification such as phosphorylation, and degradation. (asnjournals.org)
  • Nuclear factor of kappa light polypeptide gene enhancer in B-cells ( NF-kB ) is an activator of Androgen receptor gene transcription in Sertoli cells and may be an important determinant of androgen activity during spermatogenesis [ 14 ]. (bio-rad.com)
  • This gene encodes a component of a signaling pathway that regulates cell growth in response to nutrient and insulin levels. (cancer.gov)
  • There are multiple binding domains on the promoter region of the peroxisome proliferator activator receptor gamma (γ) coactivator-1 α (PGC-1α) gene, including a trio of insulin responsive elements that are activated by the Forkhead box class-O (FoxO1) winged helix transcription factor, which is known to be regulated by acute transforming retrovirus thymoma (Akt). (edu.au)
  • Two severe, progressive neurological disorders characterized by intellectual disability, autism, and developmental regression, Rett syndrome and MECP2 duplication syndrome, result from loss and gain of function, respectively, of the same critical gene, methyl-CpG-binding protein 2 ( MECP2 ). (jci.org)
  • Regulated translation initiation controls stress-induced gene expression in mammalian cells," Molecular Cell , vol. 6, no. 5, pp. 1099-1108, 2000. (hindawi.com)
  • adipose tissue
  • Of particular interest are those in vivo and in vitro studies demonstrating that the PI indinavir markedly alters the ability of insulin to stimulate glucose uptake in adipose tissue and muscle via alterations in GLUT-4 activity ( 33 , 34 ). (physiology.org)
  • glucose
  • Mice fed normal chow or HFD were fasted overnight before receiving an intraperitoneal injection of 2 g/kg glucose, and blood samples were taken at the indicated times ( n = 7-14). (nih.gov)
  • In the postprandial state, glucose uptake occurs mainly in skeletal muscle [ 1 ] through the insulin responsive glucose transporter GLUT4. (springer.com)
  • apoptosis
  • Considering that mRNA translation plays an important role in cell growth, development, malignancy, apoptosis, and response to stress, its study should provide novel insights in renal physiology and pathology. (asnjournals.org)
  • Endoplasmic reticulum stress contributes to beta cell apoptosis in type 2 diabetes," Diabetologia , vol. 50, no. 4, pp. 752-763, 2007. (hindawi.com)
  • ribosome
  • They function in forming a complex with the 40S ribosomal subunit and Met-tRNAi called the 43S preinitiation complex (PIC), recognizing the 5' cap structure of mRNA and recruiting the 43S PIC to mRNA, promoting ribosomal scanning of mRNA and regulating recognition of the AUG initiation codon, and joining of the 60S ribosomal subunit to create the 80S ribosome. (acris-antibodies.com)
  • AZD8055 inhibited mTORC1 and mTORC2 signalling and caused a switch from cap-dependent to internal ribosome entry site (IRES)-dependent translation in parental SW620 cells. (biologists.org)
  • Activated mTORC1 up-regulates protein synthesis by phosphorylating key regulators of mRNA translation and ribosome synthesis. (cancer.gov)
  • regulate
  • In vivo in Drosophila larvae, however, we found that insulin signaling can regulate protein synthesis, and thus may affect TOR activity. (biomedcentral.com)
  • We also delve into the relationship between insulin signaling and TOR, and conclude that the ability of insulin signaling to regulate TOR is dependent on cell type, and may vary within a given cell type as nutritional conditions change. (biomedcentral.com)
  • responsive
  • 21536732 ). In tissues responsive to insulin, controls fatty acid synthesis and glycolysis by exerting translational control of adipogenic transcription factors such as CEBPB, CEBPD and ATF4 that have G/C rich or uORF in their 5'UTR. (uniprot.org)
  • type 2 diabet
  • Type 1 and type 2 diabetes each have similarities in that both types of diabetes involve insulin from the pancreas not working properly as it should. (amazonaws.com)
  • Many people with type 2 diabetes start out by diet and exercise, trying to lower their weight to improve their sugars before trying any oral anti-diabetic medications. (amazonaws.com)
  • Understanding the Effects of Roux-en-Y Gastric Bypass (RYGB) Surgery on Type 2 Diabetes MellitusRaymond G. Why there is this discordant finding between HOMA-IR measures and insulin clamp studies is unclear. (amazonaws.com)
  • M. Prentki and C. J. Nolan, "Islet β cell failure in type 2 diabetes," Journal of Clinical Investigation , vol. 116, no. 7, pp. 1802-1812, 2006. (hindawi.com)
  • V. Poitout and R. P. Robertson, "Minireview: secondary β -cell failure in type 2 diabetes-a convergence of glucotoxicity and lipotoxicity," Endocrinology , vol. 143, no. 2, pp. 339-342, 2002. (hindawi.com)
  • The endoplasmic reticulum in pancreatic beta cells of type 2 diabetes patients," Diabetologia , vol. 50, no. 12, pp. 2486-2494, 2007. (hindawi.com)
  • biosynthesis
  • Taken together, these results demonstrate that regulation of lipid composition by SREBP is essential to maintain the balance between protein and lipid biosynthesis downstream of Akt and to prevent resultant ER-stress and cell death. (biomedcentral.com)
  • transcription
  • Signaling by mTORC1 caused accumulation of the transcription factor ATF4, which enhances production of the enzyme methylenetetrahydrofolate dehydrogenase 2, thus leading to increased production of the purine nucleotides needed for cell growth. (sciencemag.org)
  • Data obtained in C. elegans indicate that the beneficial effect mediated via reduced IR/IGF-1R signaling might partially be induced via the forkhead-box O transcription factors (FoxO). (hindawi.com)
  • Ambient protein levels are under coordinated control of transcription, mRNA translation, and degradation. (asnjournals.org)
  • Whereas transcription and degradation mechanisms have been studied in depth in renal science, the role of mRNA translation, the process by which peptide synthesis occurs according to the genetic code that is present in the mRNA, has not received much attention. (asnjournals.org)
  • Although synthesis of a protein involves transcription and mRNA translation, until recently, the majority of investigations have addressed transcription. (asnjournals.org)
  • Biological activity of androgens such as Testosterone and DHT is predominantly meditated by its binding to the Androgen receptor , a member of the nuclear receptor superfamily that functions as a ligand-activated transcription factor [ 3 ], [ 4 ]. (bio-rad.com)
  • These effects are considered non-genomic, as they occur in cells in the presence of inhibitors of transcription and translation and occur too rapidly to involve transcription [ 5 ], [ 6 ]. (bio-rad.com)
  • Moreover, transcription factor Forkhead box O3 ( FOXO3A ) can induce Androgen receptor expression [ 13 ]. (bio-rad.com)
  • In mammalian skeletal muscle, the Forkhead-O1 transcription factor (FoxO1) promotes protein catabolism by activating ubiquitin-protein ligases. (edu.au)
  • Protein synthesis is a complex process that includes transcription, translation, and signal transduction events. (physiology.org)
  • Thus
  • This implies that BCAAs can penetrate cells and initiate translation, independent of insulin, thus further underlining the key significance of BCAAs, especially leucine, in anabolic-anticatabolic processes. (anabolicminds.com)
  • Thus, chronically high insulin levels have been identified as risk factor for dementia. (hindawi.com)
  • TSC1
  • Genetic studies show that TSC is caused by mutations within the TSC1 or TSC2 genes that encode the protein products hamartin (≈130 kDa) and tuberin (≈200 kDa), respectively, resulting in their inability to function as a tumor suppressor ( 2 , 3 ). (pnas.org)
  • Signaling
  • mTORC1 had transcriptional effects on multiple enzymes contributing to purine synthesis, with expression of the mitochondrial tetrahydrofolate (mTHF) cycle enzyme methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) being closely associated with mTORC1 signaling in both normal and cancer cells. (sciencemag.org)
  • Multiple mechanisms of insulin signaling pathway impairment have been described in obese individuals, involving complex interactions of chronically elevated inflammatory mediators, adipokines, and the critical role of the endoplasmic reticulum (ER) stress-dependent unfolded protein response (UPR). (hindawi.com)
  • Furthermore, insulin and IGF-1-induced signaling is reduced in the brains of patients suffering from Alzheimer's disease (AD). (hindawi.com)
  • Interestingly, studies in rodents suggest that reduced insulin receptor (IR) and insulin-like growth factor-1 receptor (IGF-1R) signaling decrease AD pathology, that is, β -amyloid toxicity. (hindawi.com)
  • The effect of insulin signaling upon TOR activity varies according to cellular type and context. (biomedcentral.com)
  • Insulin-like growth factor 1 receptor (IGF1R) signaling is a complicated and regulated network essential for cells to proliferate and survive. (spandidos-publications.com)
  • IGF-1 and IGF-2 possess autocrine, paracrine and endocrine functions, and activate IGF1R signaling ( 2 ). (spandidos-publications.com)
  • K. Zhang and R. J. Kaufman, "The unfolded protein response: a stress signaling pathway critical for health and disease," Neurology , vol. 66, no. 2, pp. (hindawi.com)
  • obese
  • Epidemiological studies suggest that being obese in midlife is a risk factor for cognitive decline and dementia in later life. (hindawi.com)
  • expression of ge
  • In conclusion, insulin decreases the expression of genes involved in oxidative metabolism in healthy but not insulin resistant muscle, due to a decrease in FoxO1 phosphorylation and nuclear exclusion secondary to reduced Akt activity. (edu.au)
  • repress
  • In contrast, in muscle taken from insulin resistant humans or in palmitate treated insulin resistant myotubes, neither Akt nor FoxO1 was phosphorylated by insulin resulting in a failure for nuclear exclusion of FoxO1 total protein, and an inability for insulin to repress the mRNA expression of PGC-1α and downstream genes. (edu.au)
  • mTORC1
  • mTORC1 also acutely stimulates the de novo synthesis of pyrimidine nucleotides through a posttranslational mechanism leading to increased intracellular pools of pyrimidines available for RNA and DNA synthesis ( 2 , 3 ). (sciencemag.org)