Insulin therapy may help repair atherosclerotic lesions in diabetic patients

New research reveals that insulin applied in therapeutic doses selectively stimulates the formation of new elastic fibers in cultures of human aortic smooth muscle cells. These results advance the understanding of the molecular and cellular mechanisms of diabetic vascular disease. The study is published in the February issue of the American Journal of Pathology.

"Our results particularly endorse the use of for the treatment of in patients with type I diabetes, in which the induction of new would mechanically stabilize the developing plaques and prevent arterial occlusions," explained lead investigator Aleksander Hinek, MD, PhD, DSc, Professor, Division of Cardiovascular Research, The Hospital for Sick Children and the Department of Laboratory Medicine and Pathobiology, University of Toronto.

Primary and decreased cellular sensitivity to insulin have been implicated in the pathogenesis of impaired healing processes, atherosclerosis and hypertension, all frequently observed in patients with both type I and type II diabetes. However, the possibility of a direct contribution of insulin to the cellular and that control the production of elastic fibers (elastogenesis) has not been explored. The researchers conducted a series of experiments to determine whether low therapeutic concentrations of insulin would promote the production of elastic fibers in cultures of human aortic .

Investigators found that insulin does in fact stimulate the deposition of elastic fibers in cultures of human aortic smooth muscle cells. The data demonstrated, for the first time, that low doses of insulin induce the elastogenic effect solely through the activation of and trigger the downstream activation of the P13K signaling pathway. 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.

Importantly, the experimental data suggest that insulin-dependent initiation of the elastin gene transcription occurs after dissociation of the FoxO1 transcription factor from the specific domain identified within the elastin gene promoter. The researchers also demonstrated that insulin may facilitate the transportation of tropoelastin into the secretory endosomes, where it can associate with S-GAL/EBP, the "chaperone" protein that enhances secretion.

"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 I, or insulin resistance, in diabetes type II, contribute to the development of hypertension and the rapid progression of atherosclerosis," concluded Dr. Hinek.

Dr. Hinek further elaborated on the far-reaching effects these data provide: "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."

More information: The article is "Insulin Induces Production of New Elastin in Cultures of Human Aortic Smooth Muscle Cells," by J. Shi, A. Wang, S. Sen, Y. Wang, J. Kim, T.J. Mitts, and A. Hinek (DOI: 10.1016/j.ajpath.2011.10.022). It will appear in The American Journal of Pathology, Volume 180, Issue 2 (February 2012)

add to favorites email to friend print save as pdf

Related Stories

How does insulin influence resistin?

Jan 16, 2008

Obesity is a worldwide health problem directly linked to several diseases such as hypertension and type 2 diabetes. Resistin is a cysteine-rich hormone mainly secreted by adipose tissues and may form a biochemical link between ...

Impaired fat-burning gene worsens diabetes

Feb 07, 2008

Researchers at the Swedish medical university Karolinska Institutet have in collaboration with researchers from Finland, China, Japan and the US discovered new cellular mechanisms that lead to in insulin resistance in people ...

From managing sugar to managing healing

Dec 10, 2006

Insulin is a hormone known primarily for regulating sugar levels in the blood, yet researchers at the University of California, Riverside, recently found that applying insulin directly to skin wounds significantly enhanced ...

Exercise pivotal in preventing and fighting type II diabetes

Feb 07, 2007

One in three American children born in 2000 will develop type II diabetes, according to the U.S. Centers for Disease Control and Prevention (CDC). A new study at the University of Missouri-Columbia says that acute exercise ...

Recommended for you

NY and NJ say they will require Ebola quarantines

4 hours ago

The governors of New Jersey and New York on Friday ordered a mandatory, 21-day quarantine for all doctors and other arriving travelers who have had contact with Ebola victims in West Africa.

WHO: Mali case may have infected many people

8 hours ago

The World Health Organization says a toddler who brought Ebola to Mali was bleeding from her nose during her journey on public transport and may have infected many people.

Two US nurses are declared cured of Ebola

9 hours ago

Two American nurses were declared cured of Ebola on Friday, and one was healthy enough to leave the hospital and meet President Barack Obama for a hug.

User comments