Forgot your Password

If you have forgotten your password, please enter your account email below and we will reset your password and email you the new password.


Login to SciCrunch


Register an Account

Delete Saved Search

Are you sure you want to delete this saved search?


NIF LinkOut Portal


Hepatic muscarinic acetylcholine receptors are not critically involved in maintaining glucose homeostasis in mice.

Li JH, Gautam D, Han SJ, Guettier JM, Cui Y, Lu H, Deng C, O'Hare J, Jou W, Gavrilova O, Buettner C, Wess J


OBJECTIVE: An increase in the rate of hepatic glucose production is the major determinant of fasting hyperglycemia in type 2 diabetes. A better understanding of the signaling pathways and molecules that regulate hepatic glucose metabolism is therefore of great clinical importance. Recent studies suggest that an increase in vagal outflow to the liver leads to decreased hepatic glucose production and reduced blood glucose levels. Since acetylcholine (ACh) is the major neurotransmitter of the vagus nerve and exerts its parasympathetic actions via activation of muscarinic ACh receptors (mAChRs), we examined the potential metabolic relevance of hepatocyte mAChRs. RESEARCH DESIGN AND METHODS: We initially demonstrated that the M(3) mAChR is the only mAChR subtype expressed by mouse liver/hepatocytes. To assess the physiological role of this receptor subtype in regulating hepatic glucose fluxes and glucose homeostasis in vivo, we used gene targeting and transgenic techniques to generate mutant mice lacking or overexpressing M(3) receptors in hepatocytes only. RESULTS: Strikingly, detailed in vivo phenotyping studies failed to reveal any significant metabolic differences between the M(3) receptor mutant mice and their control littermates, independent of whether the mice were fed regular or a high-fat diet. Moreover, the expression levels of genes for various key transcription factors, signaling molecules, and enzymes regulating hepatic glucose fluxes were not significantly altered in the M(3) receptor mutant mice. CONCLUSIONS: This rather surprising finding suggests that the pronounced metabolic effects mediated by activation of hepatic vagal nerves are mediated by noncholinergic signaling pathways.

  1. Welcome

    Welcome to NIF. Explore available research resources: data, tools and materials, from across the web

  2. Community Resources

    Search for resources specially selected for NIF community

  3. More Resources

    Search across hundreds of additional biomedical databases

  4. Literature

    Search Pub Med abstracts and full text from PubMed Central

  5. Insert your Query

    Enter your search terms here and hit return. Search results for the selected tab will be returned.

  6. Join the Community

    Click here to login or register and join this community.

  7. Categories

    Narrow your search by selecting a category. For additional help in searching, view our tutorials.

  8. Query Info

    Displays the total number of search results. Provides additional information on search terms, e.g., automated query expansions, and any included categories or facets. Expansions, filters and facets can be removed by clicking on the X. Clicking on the + restores them.

  9. Search Results

    Displays individual records and a brief description. Click on the icons below each record to explore additional display options.