title: Increasing glucagon secretion could antagonize the action of exogenous insulin for glycemic control in streptozocin-induced diabetic rhesus monkeys.
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.
authors.affiliation: Laboratory of Transplant Engineering and Immunology, Regenerative Medicine Research Center, West China Hospital, Sichuan University.
authors.forename: Sirong
authors.initials: S
authors.lastname: He
authors.forename: Dan
authors.initials: D
authors.lastname: Wang
authors.forename: Yanrong
authors.initials: Y
authors.lastname: Lu
authors.forename: Younan
authors.initials: Y
authors.lastname: Chen
authors.forename: Xi
authors.initials: X
authors.lastname: Jin
authors.forename: Chengsi
authors.initials: C
authors.lastname: Wang
authors.forename: Jingming
authors.initials: J
authors.lastname: Zhao
authors.forename: Yan
authors.initials: Y
authors.lastname: Ren
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.forename: Hongxia
authors.initials: H
authors.lastname: Li
authors.forename: Jingqiu
authors.initials: J
authors.lastname: Cheng
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced* / Q000188:drug therapy* / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005934:Glucagon / Q000097:blood*; D050416:Glucagon-Secreting Cells / Q000378:metabolism / Q000473:pathology; D007004:Hypoglycemic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D007328:Insulin / Q000494:pharmacology / Q000627:therapeutic use*; D007333:Insulin Resistance / Q000502:physiology; D008137:Longitudinal Studies; D008253:Macaca mulatta; D013311:Streptozocin / Q000009:adverse effects*; D013997:Time Factors; D016896:Treatment Outcome; D014280:Triglycerides / Q000378:metabolism
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D014280:Triglycerides; D013311:Streptozocin; D005934:Glucagon
keywords: diabetic rhesus monkeys; exogenous insulin; glycemic control; insulin sensitivity; α-cell dysfunction