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The effects of insulin and liraglutide on osteoprotegerin and vascular calcification in vitro and in patients with type 2 diabetes.
- Source :
-
European journal of endocrinology [Eur J Endocrinol] 2015 Jul; Vol. 173 (1), pp. 53-61. - Publication Year :
- 2015
-
Abstract
- Objective: Vascular calcification (VC) is inhibited by the glycoprotein osteoprotegerin (OPG). It is unclear whether treatments for type 2 diabetes are capable of promoting or inhibiting VC. The present study examined the effects of insulin and liraglutide on i) the production of OPG and ii) the emergence of VC, both in vitro in human aortic smooth muscle cells (HASMCs) and in vivo in type 2 diabetes.<br />Design/methods: HASMCs were exposed to insulin glargine or liraglutide, after which OPG production, alkaline phosphatase (ALP) activity and levels of Runx2, ALP and bone sialoprotein (BSP) mRNA were measured. A prospective, nonrandomised human subject study was also conducted, in which OPG levels and coronary artery calcification (CAC) were measured in a type 2 diabetes population before and 16 months after the commencement of either insulin or liraglutide treatment and in a control group that took oral hypoglycemics only.<br />Results: Exposure to insulin glargine, but not liraglutide, was associated with significantly decreased OPG production (11 913±1409 pg/10(4) cells vs 282±13 pg/10(4) cells, control vs 10 nmol/l insulin, P<0.0001), increased ALP activity (0.82±0.06 IU/10(4) cells vs 2.40±0.16 IU/10(4) cells, control vs 10 nmol/l insulin, P<0.0001) and increased osteogenic gene expression by HASMCs. In the clinical study (n=101), insulin treatment was associated with a significant reduction in OPG levels and, despite not achieving full statistical significance, a trend towards increased CAC in patients.<br />Conclusion: Exogenous insulin down-regulated OPG in vitro and in vivo and promoted VC in vitro. Although neither insulin nor liraglutide significantly affected CAC in the present pilot study, these data support the establishment of randomised trials to investigate medications and VC in diabetes.<br /> (© 2015 European Society of Endocrinology.)
- Subjects :
- Aged
Alkaline Phosphatase metabolism
Cells, Cultured
Core Binding Factor Alpha 1 Subunit metabolism
Coronary Vessels pathology
Endpoint Determination
Female
Glucagon-Like Peptide 1 adverse effects
Glucagon-Like Peptide 1 pharmacology
Glucagon-Like Peptide 1 therapeutic use
Humans
Hypoglycemic Agents adverse effects
In Vitro Techniques
Insulin Glargine
Insulin, Long-Acting adverse effects
Liraglutide
Male
Metformin adverse effects
Metformin pharmacology
Metformin therapeutic use
Middle Aged
Muscle, Smooth, Vascular pathology
Pilot Projects
Prospective Studies
Sialoglycoproteins biosynthesis
Sialoglycoproteins genetics
Diabetes Mellitus, Type 2 complications
Diabetes Mellitus, Type 2 drug therapy
Glucagon-Like Peptide 1 analogs & derivatives
Hypoglycemic Agents pharmacology
Hypoglycemic Agents therapeutic use
Insulin, Long-Acting pharmacology
Insulin, Long-Acting therapeutic use
Osteoprotegerin blood
Vascular Calcification chemically induced
Subjects
Details
- Language :
- English
- ISSN :
- 1479-683X
- Volume :
- 173
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- European journal of endocrinology
- Publication Type :
- Academic Journal
- Accession number :
- 26036811
- Full Text :
- https://doi.org/10.1530/EJE-14-1137