Insulin Therapy May Help Repair Atherosclerotic Lesions In Diabetic Patients

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Academic Journal
Main Category: Diabetes
Article Date: 11 Jan 2012 - 9:00 PST


According to a study published in the February issue of the The American Journal of Pathology, insulin applied in low doses activates the development of new elastic fibers in cultures of human aortic smooth muscle cells. The study results provide better insights into cellular and molecular mechanisms of diabetic vascular disease.

Lead researcher, Aleksander Hinek, MD, Ph.D, DSc, Professor, Division of Cardiovascular Research, The Hospital for Sick Children and the Department of Laboratory Medicine and Pathobiology, University of Toronto, explains:

"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."

Decreased cellular sensitivity to insulin and primary insulin deficiency have been involved in the pathogenesis of impaired healing processes, hypertension and atherosclerosis, all of which are frequently seen in individuals suffering with type 1 and type 2 diabetes.

Although, researchers have not investigated the possibility of a direct contribution of insulin to the molecular and cellular mechanisms that manage the development of elastogenesis (elastic fibers).

A series of investigations were conducted by the researchers in order to find out if low doses of insulin would trigger the development of elastogenesis in cultures of human aortic smooth muscle cells.

They discovered that insulin activates the degradation of elastic fibers in cultures of human aortic smooth muscle cells. For the first time, data showed that low therapeutic concentrations of insulin trigger the elastogenic effect singularly via the activation of the insulin receptor and induce the downstream activation of the P13K signaling pathway.

The researchers discovered that the ultimate up-regulation of elastogenesis deposition by insulin is accomplished via two parallel mechanisms, the first being the start of elastin gene expression and the second enhancing the tropoelastin secretion.

Significantly, experimental data from the investigation indicate that insulin-dependent activation of the elastin gene transcription happens after separation of the FoxO1 transcription factor from the specific domain detected within the elastin gene promoter.

In addition, the findings also demonstrate that insulin might help tropoelastin travel into the secretory endosomes, where it can be linked to S-GAL/EBP, the protein that improves 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.

Importantly, our newest results indicate that the discovered elastogenic effect of low concentrations (0.5-10nM) 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) systematic 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."

Written by Grace Rattue
Copyright: Medical News Today
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