Insulin and its analogue glargine do not affect viability and proliferation of human coronary artery endothelial and smooth muscle cells

Abstract

Aims/hypothesis: Present guidelines for the treatment of type 2 diabetes recommend HbA 1 c values of less than 7%. As beta cell function worsens during progress of the disease, insulin therapy is often necessary to achieve this ambitious goal. However, due to peripheral insulin resistance, many patients need rather high insulin dosages. In the light of the extremely high cardiovascular risk of diabetic patients, it is important to determine whether high concentrations of insulin or its frequently used analogues are harmful to the cardiovascular system. We therefore investigated the modulatory effects of regular human insulin and its analogue glargine on proliferation and apoptosis of human coronary artery endothelial cells (HCAECs) and human coronary artery smooth muscle cells (HCASMCs). Methods: Cells were treated with regular human insulin or insulin glargine. Proliferation was determined by [ 3 H]thymidine incorporation and by flow cytometric analysis of Ki-67 expression. Apoptosis was assessed by flow cytometry (cell cycle analysis and annexin V staining) and determination of caspase-3 activity. Results: HCAECs and HCASMCs treated with regular human insulin or insulin glargine did not show significant increases in DNA synthesis or Ki-67 expression. Administration of regular human insulin or insulin glargine did not modulate the extent of apoptotic events. No influence of insulin on lipoapoptotic vascular cell death could be detected.Conclusions/interpretation: Taken together, neither regular human insulin nor insulin glargine influences growth and apoptosis of human coronary artery cells in vitro. Our data do not suggest that regular human insulin or insulin glargine promote atherosclerosis through mechanisms affecting the cellularity of human coronary arteries.

Insulin analogues display IGF‐I‐like mitogenic and anti‐apoptotic activities in cultured cancer cells

“…Although an increase in mortality rate was observed in male rats at every glargine dose and in female rats in the high-dose glargine group, these results are consistent with the prevailing view that regular insulin and insulin analogues, per se, do not induce malignant transformation. Furthermore, neither regular insulin nor glargine were shown to affect viability and proliferation of non-transformed human coronary endothelial and smooth muscle cells [30].…”

Saturated, but Not Unsaturated, Fatty Acids Induce Apoptosis of Human Coronary Artery Endothelial Cells via Nuclear Factor-κB Activation

“…Since increasing evidence, mainly from histological examinations, suggests endothelial cell apoptosis to play an important role in atherogenesis, plaque erosion, and acute coronary syndromes (7,8), we studied the susceptibility of endothelial and smooth muscle cells from human coronary arteries toward NEFA-induced apoptosis (lipoapoptosis). As we recently reported, the saturated NEFAs palmitate and stearate, at high physiological concentrations, provoke substantial apoptotic events in human coronary artery endothelial cells (HCAECs) and a mixed form of apoptosis and necrosis in human coronary artery smooth muscle cells (9). To further characterize these findings, we investigated in this study the role of selected saturated versus unsaturated NEFAs in HCAEC lipoapoptosis and the underlying molecular mechanisms.…”

IGF-1 receptor signalling determines the mitogenic potency of insulin analogues in human smooth muscle cells and fibroblasts

“…Most of these studies were done in tumour cell lines or in cell systems overexpressing the human InsR and thus do not represent the normal status of primary human cells. Recently, Staiger et al [23] reported that glargine and human insulin are not different in their proliferative effects on human coronary artery endothelial and smooth muscle cells.…”