Insulin therapy may help repair atherosclerotic lesions in diabetic patients

New research published in the American Journal of Pathology

 

Philadelphia, PA, USA (January 9, 2012) – 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 insulin therapy for the treatment of atherosclerotic lesions in patients with type I diabetes, in which the induction of new elastic fibers 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 insulin deficiency 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 molecular mechanisms 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 smooth muscle cells.

 

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 insulin receptor 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."

 

 

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) published by Elsevier.

 

 


Elsevier Health Sciences, 09.01.2012 (tB).

MEDICAL NEWS

IU School of Medicine researchers develop blood test for anxiety
COVID-19 pandemic increased rates and severity of depression, whether people…
COVID-19: Bacterial co-infection is a major risk factor for death,…
Regenstrief-led study shows enhanced spiritual care improves well-being of ICU…
Hidden bacteria presents a substantial risk of antimicrobial resistance in…

SCHMERZ PAINCARE

Hydromorphon Aristo® long ist das führende Präferenzpräparat bei Tumorschmerz
Sorgen und Versorgen – Schmerzmedizin konkret: „Sorge als identitätsstiftendes Element…
Problem Schmerzmittelkonsum
Post-Covid und Muskelschmerz
Kopfschmerz bei Übergebrauch von Schmerz- oder Migränemitteln

DIABETES

Wie das Dexom G7 abstrakte Zahlen mit Farben greifbar macht…
Diabetes mellitus: eine der großen Volkskrankheiten im Blickpunkt der Schmerzmedizin
Suliqua®: Einfacher hin zu einer guten glykämischen Kontrolle
Menschen mit Diabetes während der Corona-Pandemie unterversorgt? Studie zeigt auffällige…
Suliqua® zur Therapieoptimierung bei unzureichender BOT

ERNÄHRUNG

Positiver Effekt der grünen Mittelmeerdiät auf die Aorta
Natriumaufnahme und Herz-Kreislaufrisiko
Tierwohl-Fleisch aus Deutschland nur mäßig attraktiv in anderen Ländern
Diät: Gehirn verstärkt Signal an Hungersynapsen
Süßigkeiten verändern unser Gehirn

ONKOLOGIE

Strahlentherapie ist oft ebenso effizient wie die OP: Neues vom…
Zanubrutinib bei chronischer lymphatischer Leukämie: Zusatznutzen für bestimmte Betroffene
Eileiter-Entfernung als Vorbeugung gegen Eierstockkrebs akzeptiert
Antibiotika als Störfaktor bei CAR-T-Zell-Therapie
Bauchspeicheldrüsenkrebs: Spezielle Diät kann Erfolg der Chemotherapie beeinflussen

MULTIPLE SKLEROSE

Multiple Sklerose: Aktuelle Immunmodulatoren im Vergleich
Neuer Biomarker für Verlauf von Multipler Sklerose
Multiple Sklerose: Analysen aus Münster erhärten Verdacht gegen das Epstein-Barr-Virus
Aktuelle Daten zu Novartis Ofatumumab und Siponimod bestätigen Vorteil des…
Multiple Sklerose durch das Epstein-Barr-Virus – kommt die MS-Impfung?

PARKINSON

Meilenstein in der Parkinson-Forschung: Neuer Alpha-Synuclein-Test entdeckt die Nervenerkrankung vor…
Neue Erkenntnisse für die Parkinson-Therapie
Cochrane Review: Bewegung hilft, die Schwere von Bewegungssymptomen bei Parkinson…
Technische Innovationen für eine maßgeschneiderte Parkinson-Diagnostik und Therapie
Biomarker und Gene: neue Chancen und Herausforderungen für die Parkinson-Diagnose…