Metabolic effect and receptor signalling profile of a non-metabolisable insulin glargine analogue. (October 2014)

• Record Type: Journal Article
• Authors: Werner, Ulrich; Korn, Marcus; Schmidt, Ronald; Wendrich, Thomas M.; Tennagels, Norbert
• Is Part Of: Archives of physiology and biochemistry. Volume 120:Number 4(2014)
• Page Start: 158
• Page End: 165
• Publication Date: 2014-10
• Subjects: Physiology -- Periodicals; Biochemistry -- Periodicals; Biophysics -- Periodicals; Biochemistry; Physiology; 571
• DOI: 10.3109/13813455.2014.950589
• Languages: English
• ISSNs: 1381-3455

Abstract

<abstract> <title>Abstract</title> <p> <italic>Context</italic>: Insulin glargine (GLA) is rapidly metabolized <italic>in vivo</italic> to metabolite M1, which has <italic>in vitro</italic> metabolic and mitogenic profiles comparable with human insulin (HI).</p> <p> <italic>Objective</italic>: To investigate the pharmacologic and signalling profiles of a non-metabolizable analogue (A21Gly, DiD-Arg) insulin (D-GLA).</p> <p> <italic>Methods</italic>: Rats were injected s.c. with 1, 12.5 or 200 U/kg of GLA or D-GLA; blood glucose and phosphorylation status of the insulin receptor (IR), Akt and IGF-1 receptor (IGF1R) in tissue samples were investigated after 1 h. Plasma samples were analysed for insulin by LC-MS/MS.</p> <p> <italic>Results</italic>: Blood glucose lowering was prolonged with D-GLA. D-GLA comprised ≥98% of insulin after D-GLA injection; M1 comprised 76–92% after GLA injection. IR and Akt phosphorylation were comparable with GLA and D-GLA. Neither analogue stimulated IGF1R phosphorylation.</p> <p> <italic>Conclusions</italic>: Suprapharmacological doses of D-GLA did not activate IGF1R <italic>in vivo</italic>. Mitogenic effects of insulin and insulin analogues might be solely based on IR growth-promoting activity.</p> </abstract>