title: Insulin and its analogue glargine do not affect viability and proliferation of human coronary artery endothelial and smooth muscle cells.
abstract: OBJECTIVE
  Present guidelines for the treatment of type 2 diabetes recommend HbA1c 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 [3H]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
  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.
authors.affiliation: Internal Medicine IV, University of Tübingen, Otfried-Muller-Str. 10, 72076 Tübingen, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Staiger
authors.forename: H
authors.initials: H
authors.lastname: Staiger
authors.forename: M A
authors.initials: MA
authors.lastname: Schweitzer
authors.forename: E
authors.initials: E
authors.lastname: Metzinger
authors.forename: B
authors.initials: B
authors.lastname: Balletshofer
authors.forename: H-U
authors.initials: HU
authors.lastname: Häring
authors.forename: M
authors.initials: M
authors.lastname: Kellerer
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects*; D002478:Cells, Cultured; D003331:Coronary Vessels / Q000166:cytology* / Q000187:drug effects; D004247:DNA / Q000096:biosynthesis; D004730:Endothelium, Vascular / Q000166:cytology* / Q000187:drug effects; D005434:Flow Cytometry; D006801:Humans; D007328:Insulin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000069036:Insulin Glargine; D049528:Insulin, Long-Acting; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000187:drug effects; D019308:Palmitic Acid / Q000494:pharmacology; D013229:Stearic Acids / Q000494:pharmacology
chemical_list: D007328:Insulin; D049528:Insulin, Long-Acting; D013229:Stearic Acids; D019308:Palmitic Acid; D000069036:Insulin Glargine; C031183:stearic acid; D004247:DNA