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    Increasing glucagon secretion could antagonize the action of exogenous insulin for glycemic control in streptozocin-induced diabetic rhesus monkeys

    Access Status
    Fulltext not available
    Authors
    He, S.
    Wang, D.
    Lu, Y.
    Chen, Younan
    Jin, X.
    Wang, C.
    Zhao, J.
    Ren, Y.
    Wang, L.
    Li, H.
    Cheng, J.
    Date
    2013
    Type
    Journal Article
    
    Metadata
    Show full item record
    Citation
    He, S. and Wang, D. and Lu, Y. and Chen, Y. and Jin, X. and Wang, C. and Zhao, J. et al. 2013. Increasing glucagon secretion could antagonize the action of exogenous insulin for glycemic control in streptozocin-induced diabetic rhesus monkeys. Experimental Biology and Medicine. 238 (4): pp. 385-391.
    Source Title
    Experimental Biology and Medicine
    DOI
    10.1177/1535370213477974
    ISSN
    1535-3702
    School
    School of Biomedical Sciences
    URI
    http://hdl.handle.net/20.500.11937/24235
    Collection
    • Curtin Research Publications
    Abstract

    Although intraislet insulin signaling is known to play a critical role in regulating glucagon secretion, it is unknown whether abnormal glucagon secretion influences the hypoglycemic effect of exogenous insulin with intraislet insulin deletion. We performed a longitudinal study using 16 streptozocin (STZ)-induced diabetic rhesus monkeys to explore a-cell function under the absence ß-cells and to assess whether increasing glucagon secretion antagonizes the action of exogenous insulin for glycemic control. We found that although the a-cells were impaired and the basal secretion levels of glucagon decreased rapidly after STZ (80-90 mg/kg) administration, as based on long-term observation post-STZ injection, glucagon secretion and the number of a-cells were increased. Glycemic control was increasingly difficult, the insulin resistance (HOMA-IR) index was significantly higher, and the triglycerides (TG) levels were gradually decreased. Moreover, a significant correlation between the levels of glucagon and HOMA-IR was found. Under the long-term absence of ß-cells, the inhibitory effect on a-cell activity is profoundly attenuated, leading to an increase in glucagon secretion and the amount of a-cells and even a-cell dysfunction. Increased glucagon levels have a serious impact on the insulin sensitivity in vivo and result in an antagonization of the hypoglycemic effect of exogenous insulin. © 2013 by the Society for Experimental Biology and Medicine.

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