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  • 1
    Digitale Medien
    Digitale Medien
    Oxford, UK : Blackwell Science Ltd
    Journal of neurochemistry 93 (2005), S. 0 
    ISSN: 1471-4159
    Quelle: Blackwell Publishing Journal Backfiles 1879-2005
    Thema: Medizin
    Notizen: While considerable research has examined diminished insulin responses within peripheral tissues, comparatively little has been done to examine the effects of this metabolic disruption upon the CNS. The present study employed biochemical and electrophysiological assays of acutely prepared brain slices to determine whether neural insulin resistance is a component of the metabolic syndrome observed within the fructose-fed (FF) hamster. The tyrosine phosphorylation levels of the insulin receptor (IR) and insulin receptor substrate 1 (IRS-1) in response to insulin were significantly reduced within FF hamsters. Also, insulin-mediated phosphorylation of both residues necessary for activation of the serine-threonine kinase Akt/PKB, a key effector of insulin signaling, was markedly decreased. Elevated levels of the protein tyrosine phosphatase 1B, which dephosphorylates the IR and IRS-1, were also observed within the cerebral cortex and hippocampus of FF hamsters. Examination of whether a nutritionally induced compromise of neural insulin signaling altered synaptic function revealed a significant attenuation of insulin-induced long-term depression, but no effect upon either paired-pulse facilitation or electrically induced long-term potentiation. Collectively, our results demonstrate, for the first time, that nutritionally induced insulin resistance significantly affects the neural insulin signaling pathway, and suggest that brain insulin resistance may contribute to cognitive impairment.
    Materialart: Digitale Medien
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 2
    facet.materialart.
    Unbekannt
    American Physiological Society
    In:  American Journal of Physiology-Endocrinology and Metabolism, 317 (4). E559-E572.
    Publikationsdatum: 2020-01-02
    Beschreibung: Nutrient sensing plays an important role in ensuring that appropriate digestive or hormonal responses are elicited following the ingestion of fuel substrates. Mechanisms of nutrient sensing in the oral cavity have been fairly well characterized and involve lingual taste receptors. These include heterodimers of G protein-coupled receptors (GPCRs) of the taste receptor type 1 (T1R) family for sensing sweet (T1R2-T1R3) and umami (T1R1-T1R3) stimuli, the T2R family for sensing bitter stimuli, and ion channels for conferring sour and salty tastes. In recent years, several studies have revealed the existence of additional nutrient-sensing mechanisms along the gastrointestinal tract. Glucose sensing is achieved by the T1R2-T1R3 heterodimer on enteroendocrine cells, which plays a role in triggering the secretion of incretin hormones for improved glycemic and lipemic control. Protein hydrolysates are detected by Ca2+-sensing receptor, the T1R1-T1R3 heterodimer, and G protein-coupled receptor 92/93 (GPR92/93), which leads to the release of the gut-derived satiety factor cholecystokinin. Furthermore, several GPCRs have been implicated in fatty acid sensing: GPR40 and GPR120 respond to medium- and long-chain fatty acids, GPR41 and GPR43 to short-chain fatty acids, and GPR119 to endogenous lipid derivatives. Aside from the recognition of fuel substrates, both the oral cavity and the gastrointestinal tract also possess T2R-mediated mechanisms of recognizing nonnutrients such as environmental contaminants, bacterial toxins, and secondary plant metabolites that evoke a bitter taste. These gastrointestinal sensing mechanisms result in the transmission of neuronal signals to the brain through the release of gastrointestinal hormones that act on vagal and enteric afferents to modulate the physiological response to nutrients, particularly satiety and energy homeostasis. Modulating these orally accessible nutrient-sensing pathways using particular foods, dietary supplements, or pharmaceutical compounds may have therapeutic potential for treating obesity and metabolic diseases.
    Materialart: Article , PeerReviewed
    Format: text
    Standort Signatur Einschränkungen Verfügbarkeit
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