Loading...
  • metabolic
  • Mice with targeted disruption of the IRS-1 or IRS-2 gene show either insulin resistance ( 11 , 12 ) or type 2 diabetes ( 13 ), respectively, whereas IRS-3 and IRS-4 knockout mice have only minimal metabolic abnormalities ( 14 , 15 ). (diabetesjournals.org)
  • and (3) introduce collaborative nutritional and metabolic strategies to conserve lean body mass and improve surgical outcome. (asahq.org)
  • To maintain its high energy demands, the heart is capable of using many metabolic substrates. (ahajournals.org)
  • The tumor suppressor kinase LKB1 has been identified as a physiologic activator of the key metabolic regulator 5'-AMP-activated protein kinase, establishing a possible molecular link between the regulation of metabolism and cell proliferation. (springer.com)
  • T2DM is also a metabolic disease characterized by chronic hyperglycaemia, along with various comorbidities, such as cardiovascular disease, obesity, microangiopathy and renal failure [ 3 ]. (ijbs.com)
  • insulin resistance
  • 3 , 4 There are many molecular mechanisms that contribute to the association between insulin resistance and increased cardiovascular disease. (ahajournals.org)
  • For example, the insulin-induced vasodilation is impaired due to defects in PI3-kinase signaling in insulin resistance [ 8 , 9 ]. (hindawi.com)
  • The results demonstrate that the causes of insulin resistance in denervated muscles are dependent on time after surgery. (physiology.org)
  • The signs of insulin resistance in the denervated rat muscles in vivo can be observed as early as 3 h after sectioning the nerve (the earliest time tested) ( 16 ). (physiology.org)
  • We have previously demonstrated that both slow-twitch and fast-twitch muscles exhibit a progressive lowering of insulin-induced glucose uptake in vivo during the first 24 h after sectioning the sciatic nerve but that the two kinds of muscles differ in the manifestations of insulin resistance at 3-17 days after denervation ( 16 ). (physiology.org)
  • A variety of agents and conditions that induce insulin resistance, such as TNFα and free fatty acids, activate a number of protein kinases that target elements along the insulin-signaling pathway. (physiology.org)
  • We outline the relations between inflammation, stress responses, the activation of IRS kinases, and the induction of insulin resistance, and we propose a few directions for future studies in this field. (physiology.org)
  • intracellular
  • To identify the intracellular signals which increase the adhesiveness of leukocyte function-associated antigen 1 (LFA-1), we established an assay system for activation-dependent adhesion through LFA-1/intercellular adhesion molecule 1 ICAM-1 using mouse lymphoid cells reconstituted with human LFA-1 and then introduced constitutively active forms of signaling molecules. (asm.org)
  • These stimuli are thought to generate intracellular second messengers through cell surface receptors, leading to alteration of the adhesive state of LFA-1 ( 3 , 49 , 70 ). (asm.org)
  • inhibits
  • AKT is a major kinase that potently inhibits the activity of FoxOs by phosphorylating the well-conserved sites in FoxOs: FoxO1-T24/S256/S319, FoxO3-T32/S253/S315, FoxO4-T32/S197/S262, and FoxO6-T26/S184 ( 5 ). (diabetesjournals.org)
  • cellular
  • Protein interactions are essential for most cellular functions. (biomedcentral.com)
  • Selective protein-protein interactions are important for many cellular functions and are often mediated by short regions, but such regions are difficult to identify because of their short lengths and degenerate sequences. (biomedcentral.com)
  • AMPK (AMP-activated protein kinase) is a key regulator of cellular and whole-body energy balance. (clinsci.org)
  • Second messengers can be derived from phospholipids in the membrane by the action of the enzymes phospholipase C or phosphoinositide-3-OH kinase (PI(3)K). PI(3)K is a key player in many cellular responses, including the movement of organelle membranes, shape alteration through rearrangement of cytoskeletal actin, transformation and chemotaxis. (embl-heidelberg.de)
  • Autophagic activity affects the pathogenesis of diverse diseases, such as cancer, neurodegenerative and infectious diseases [ 5 ], as it degrades toxic intracytoplasmic contents (such as aggregate-prone proteins and various bacteria), but also serves as a buffer against cellular starvation by generating amino acids and other macromolecules. (biochemsoctrans.org)
  • Phosphoinositides are membrane-bound signalling molecules that regulate cell proliferation and survival, cytoskeletal reorganization and vesicular trafficking by recruiting effector proteins to cellular membranes. (biochemj.org)
  • Therefore the 5-ptases are a significant family of signal-modulating enzymes that govern a plethora of cellular functions by regulating the levels of specific phosphoinositides. (biochemj.org)
  • N-cadherin cooperates with the FGF receptor, leading to overexpression of MMP-9 and cellular invasion (3). (cellsignal.com)
  • The association of PCTAIRE-like proteins with cyclins has not been widely studied, although PFTAIRE-1 has been shown to function as a CDK which is regulated by cyclin D3 as well as the membrane-associated cyclin Y. PCTAIRE-like proteins show unusual expression patterns with high levels in post-mitotic tissues, suggesting that they may be involved in regulating post-mitotic cellular events. (umbc.edu)
  • A particular PKC isotype has been shown to regulate a specific cellular function that reflects its cellular localization and substrate preferences ( 16 , 40 , 68 ). (asm.org)
  • MAPK
  • The p44/42 MAPK (Erk1/2) signaling pathway can be activated in response to a diverse range of extracellular stimuli including mitogens, growth factors, and cytokines (1-3), and research investigators consider it an important target in the diagnosis and treatment of cancer (4). (cellsignal.com)
  • small-molecule
  • That said, the recent development of small molecule inhibitors of GSK-3 has provided new tools for visualizing the cell from the perspective of GSK-3. (biologists.org)
  • synthesis
  • A facile base-promoted sulfur-centered radical generation mode and a single-step protocol for the synthesis of thiophene derivatives using 1,3-diynes via the interaction between elemental sulfur and NaOtBu has been reported. (jove.com)
  • This PtdIns3P is also the substrate for the synthesis by PIPkin-IIIs of PtdIns(3,5)P 2 . (sigmaaldrich.com)
  • mutants
  • Serial in vitro and in vivo experiments verified that FoxO1/3a are bona fide substrates of SCP4, including in vitro dephosphorylation assays using purified enzymes, substrates, and phosphatase-inactive mutants. (diabetesjournals.org)
  • molecules
  • 2 Using Connectivity Map, 3 which combines the resistance gene expression signature with a database of expression profiles of bioactive small molecules, we identified several molecules as agents potentially able to reverse resistance to PUVA with or without interferon-α therapy. (haematologica.org)
  • The biogenesis of mammalian (and yeast) autophagosomes also involves two ubiquitin-like molecules, Atg12 and LC3 (light chain 3)/Atg8 [ 2 , 4 ]. (biochemsoctrans.org)
  • CD11a/CD18) is one of the integrins (β2 integrins) exclusively expressed on leukocytes, and its counterligands are the intercellular adhesion molecules 1, 2, and 3 (ICAM-1, -2, and -3) ( 13 , 35 , 59 ). (asm.org)
  • motifs
  • Short linear motifs (SLiMs) are also identified as specific sequence patterns that are over-represented in proteins that bind to a common partner, but the algorithms used to discover SLiMs employ filters to remove homologous proteins whereas the ELM-discovery algorithms do not. (biomedcentral.com)
  • Akt1
  • a and d ) Akt kinase activity was measured in muscle lysates (500 μg) that were subjected to immunoprecipitation with either an antibody that recognizes both Akt1 and Akt2, or an Akt3 antibody. (nih.gov)
  • Basal and insulin-stimulated activity of Akt1 kinase and uptake of 2-deoxy- d -glucose (2-DG) were measured in soleus (slow-twitch) and plantaris (fast-twitch) muscles of rats at 1 and 3 days after sectioning the sciatic nerve in one hindlimb of the animals. (physiology.org)
  • At 1 day after surgery, the insulin-stimulated activity of Akt1 kinase in denervated soleus and plantaris muscles remained unchanged, but the insulin-stimulated 2-DG uptake by these muscles was reduced by 71 and 61%, respectively, compared with the corresponding muscles of the contralateral sham (control) hindlimb. (physiology.org)
  • At 3 days, the insulin-stimulated activity of Akt1 kinase in the denervated soleus and plantaris muscles was 86 and 71% lower, respectively, than in their sham counterparts. (physiology.org)
  • None of the denervated muscles showed a decrease in the abundance of Akt1 kinase. (physiology.org)