Increasing glucagon secretion could antagonize the action of exogenous insulin for glycemic control in streptozocin-induced diabetic rhesus monkeys. (April 2013)

• Record Type: Journal Article
• Authors: He, Sirong; Wang, Dan; Lu, Yanrong; Chen, Younan; Jin, Xi; Wang, Chengsi; Zhao, Jingming; Ren, Yan; Wang, Li; Li, Hongxia; Cheng, Jingqiu
• Is Part Of: Experimental biology and medicine. Volume 238:Number 4(2013)
• Page Start: 385
• Page End: 391
• Publication Date: 2013-04
• Subjects: α-cell dysfunction -- diabetic rhesus monkeys -- exogenous insulin -- glycemic control -- insulin sensitivity; Physiology -- Periodicals; Biology, Experimental -- Periodicals; Medicine, Experimental -- Periodicals; 610.72
• DOI: 10.1177/1535370213477974
• Languages: English
• ISSNs: 1535-3702

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 α -cell function under the absence β -cells and to assess whether increasing glucagon secretion antagonizes the action of exogenous insulin for glycemic control. We found that although the α -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 α -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 β -cells, the inhibitory effect on α -cell activity is profoundly attenuated, leading to an increase in glucagon secretion and the amount of α -cells and even α -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.