Related Experiment Video
Updated: Apr 25, 2026

Glucose Uptake Measurement and Response to Insulin Stimulation in In Vitro Cultured Human Primary Myotubes
Published on: June 25, 2017
Metabolic effect and receptor signalling profile of a non-metabolisable insulin glargine analogue
Ulrich Werner1, Marcus Korn, Ronald Schmidt
1R&D Diabetes Division .
Context:
Insulin glargine (GLA) is rapidly metabolized in vivo to metabolite M1, which has in vitro metabolic and mitogenic profiles comparable with human insulin (HI).
Objective:
To investigate the pharmacologic and signalling profiles of a non-metabolizable analogue (A21Gly,DiD-Arg) insulin (D-GLA).
Methods:
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.
Results:
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.
Conclusions:
Suprapharmacological doses of D-GLA did not activate IGF1R in vivo. Mitogenic effects of insulin and insulin analogues might be solely based on IR growth-promoting activity.
Related Concept Videos
Insulin: The Receptor and Signaling Pathways
Glucagon-like Receptor Agonists
GLP-1, when administered in high doses intravenously, triggers insulin secretion, inhibits glucagon release, slows gastric emptying, reduces food intake, and restores normal insulin secretion. However, its rapid inactivation by...
Oral Hypoglycemic Agents: Glinides
Insulin: Dosing Regimen and Adverse Effects
The basal dose constitutes about 40%-50% of the total daily dose, with the rest as premeal insulin. The mealtime insulin dose should mirror...
Hormones Regulating Blood Glucose
In addition to accelerating glucose uptake and utilization, insulin has...
Oral Hypoglycemic Agents: Biguanides and Glitazones

