Format

Send to

Choose Destination
  • Showing results for effect of the long-acting insulin analogues glargine AND degludec on cardiomyocyte cell signalling AND function. Your search for TEFFECT OF THE LONG-ACTING INSULIN ANALOGUES GLARGINE AND DEGLUDEC ON CARDIOMYOCYTE CELL SIGNALLING AND FUNCTION retrieved no results.
Cardiovasc Diabetol. 2016 Jul 15;15:96. doi: 10.1186/s12933-016-0410-9.

Effect of the long-acting insulin analogues glargine and degludec on cardiomyocyte cell signalling and function.

Author information

1
German Diabetes Center, Paul-Langerhans-Group for Integrative Physiology, Auf'm Hennekamp 65, 40225, Düsseldorf, Germany.
2
Institute for Clinical Biochemistry and Pathobiochemistry, German Diabetes Center, 40225, Düsseldorf, Germany.
3
German Center for Diabetes Research (DZD), Neuherberg, 85764, Munich, Germany.
4
Department of Endocrinology, Ghent University Hospital, 9000, Ghent, Belgium.
5
R&D Diabetes Division, Sanofi-Aventis Deutschland GmbH, 65929, Frankfurt, Germany.
6
German Diabetes Center, Paul-Langerhans-Group for Integrative Physiology, Auf'm Hennekamp 65, 40225, Düsseldorf, Germany. eckel@uni-duesseldorf.de.
7
German Center for Diabetes Research (DZD), Neuherberg, 85764, Munich, Germany. eckel@uni-duesseldorf.de.

Abstract

BACKGROUND:

The effects of insulin on cardiomyocytes, such as positive inotropic action and glucose uptake are well described. However, in vitro studies comparing long-acting insulin analogues with regard to cardiomyocyte signalling and function have not been systematically conducted.

METHODS:

Insulin receptor (IR) binding was assessed using membrane embedded and solubilised IR preparations. Insulin signalling was analysed in adult rat ventricular myocytes (ARVM) and HL-1 cardiac cells. Inotropic effects were examined in ARVM and the contribution of Akt to this effect was assessed by specific inhibition with triciribine. Furthermore, beating-rate in Cor.4U(®) human cardiomyocytes, glucose uptake in HL-1 cells, and prevention from H2O2 induced caspase 3/7 activation in cardiac cells overexpressing the human insulin receptor (H9c2-E2) were analysed. One-way ANOVA was performed to determine significance between conditions.

RESULTS:

Insulin degludec showed significant lower IR affinity in membrane embedded IR preparations. In HL-1 cardiomyocytes, stimulation with insulin degludec resulted in a lower Akt(Ser(473)) and Akt(Thr(308)) phosphorylation compared to insulin, insulin glargine and its active metabolite M1 after 5- and 10-min incubation. After 60-min treatment, phosphorylation of Akt was comparable for all insulin analogues. Stimulation of glucose uptake in HL-1 cells was increased by 40-60 %, with a similar result for all analogues. Incubation of electrically paced ARVM resulted for all insulins in a significantly increased sarcomere shortening, contractility- and relaxation-velocity. This positive inotropic effect of all insulins was Akt dependent. Additionally, in Cor.4U(®) cardiomyocytes a 10-20 % increased beating-rate was detected for all insulins, with slower onset of action in cells treated with insulin degludec. H9c2-E2 cells challenged with H2O2 showed a fivefold increase in caspase 3/7 activation, which could be abrogated by all insulins used.

CONCLUSIONS:

In conclusion, we compared for the first time the signalling and functional impact of the long-acting insulin analogues insulin glargine and insulin degludec in cardiomyocyte cell models. We demonstrated similar efficacy under steady-state conditions relative to regular insulin in functional endpoint experiments. However, it remains to be shown how these results translate to the in vivo situation.

KEYWORDS:

Cardiac action; Insulin analogues; Insulin degludec; Insulin glargine

PMID:
27422524
PMCID:
PMC4946153
DOI:
10.1186/s12933-016-0410-9
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for BioMed Central Icon for PubMed Central
Loading ...
Support Center