Diabetes patients are more susceptible to the development of atherosclerosis than non-diabetics and insulin therapy might help repair atherosclerotic lesions in diabetic patients….
Researchers at the Hospital for Sick Children and the Department of Laboratory Medicine and Pathobiology, University of Toronto reported that insulin applied in therapeutic doses selectively stimulates the formation of new elastic fibers in cultures of human aortic smooth muscle cells.
The researchers noted that their results advance the understanding of the molecular and cellular mechanisms of diabetic vascular disease.
Lead investigator Aleksander Hinek, MD, PhD, DSc, Professor, Division of Cardiovascular Research stated that, “Our results particularly endorse the use of insulin therapy for the treatment of atherosclerotic lesions in patients with type 1 diabetes, in which the induction of new elastic fibers would mechanically stabilize the developing plaques and prevent arterial occlusions.”
Primary insulin deficiency and decreased cellular sensitivity to insulin (insulin resistance) have been associated with the development of atherosclerosis, impaired healing, and hypertension. Arterial damage increases the risk of myocardial infarctions (heart attacks) and strokes. The investigators set out to determine whether low therapeutic concentrations of insulin would promote the production of elastic fibers in tissue cultures of human aortic smooth muscle cells.
The researchers found that insulin did indeed stimulate the deposition of elastic fibers in the tissue cultures. They noted that their results demonstrated, for the first time, that low doses of insulin induce the elastogenic effect solely through the activation of insulin receptor and trigger the downstream activation of the P13K signaling pathway. In addition, they explained, the ultimate up-regulation of elastic fiber deposition by insulin is executed through two parallel mechanisms: the initiation of elastin gene expression and the enhancement of tropoelastin secretion.
Dr. Hinek concluded, “We believe that our discovery of the elastogenic action of insulin allows for better understanding of the pathologic mechanisms in which the lack of insulin, in diabetes type 1, or insulin resistance, in diabetes type 2, contribute to the development of hypertension and the rapid progression of atherosclerosis.” He added, “Importantly, our newest results indicate that the discovered elastogenic effect of low concentrations (0.5-10 nM) of insulin is not restricted to the arterial smooth muscle cells. Thus, insulin also stimulates formation of elastic fibers by human skin fibroblasts and by myofibroblasts isolated from human hearts. These observations constitute a real novelty in the field of regenerative medicine and endorse 1) local application of small doses of insulin for ameliorating difficult healing of dermal wounds in diabetic patients and 2) systemic administration of insulin in patients after heart infarctions, in hope that insulin-induced elastic fiber deposition may alleviate formation of maladaptive collagenous scars in the myocardium.”
The American Journal of Pathology, Jan. 2012