A study led by the University of Barcelona proved that low-density proteins (VLDL) can worsen insulin resistance, a disease that favours the development of type 2 diabetes. According to the researchers, these results, obtained in mice, point that the increase of VLDL, the particles that carry lipids such as triglycerides in the blood, can benefit insulin resistance, and therefore, increase the risk of suffering from this type of diabetes.
The study, published in the scientific journal Diabetologia , has been carried out by the research group led by Manuel Vázquez Carrera, researcher from the Department of Pharmacology, Toxicology and Therapeutic Chemistry and the Institute of Biomedicine of the UB (IBUB), and member of the Diabetes and Associated Metabolic Diseases Networking Biomedical Research Center (CIBERdem). Researchers from the Department of Biochemistry and Molecular Biology of the UB, the Research Institute of the Hospital de la Santa Creu i Sant Pau (HSCSP-IR) and the University of Connecticut have also participated in the study.
Insulin is a hormone created by the pancreas which helps glucose to enter the cells and get energy. Insulin resistance is the condition in which normal amounts of this hormone are not enough to fulfil their role. This situation can cause type 2 diabetes, a chronic disease which, if not properly controlled, can cause problems in blood circulation, heart, eyes, kidneys and other organs.
Study with mice muscular cells
The study was conducted with mice muscular cells, which are part of the tissue that uses more glucose as a response to insulin, willing to check the impact of the VLDL increase on insulin resistance. “So far, we knew insulin resistance causes atherogenic dyslipidaemia, which starts due an increase of VLDL, and therefore triglycerides, which ends up causing a decrease of HDL cholesterol and of the smallest and most dense LDL cholesterol particles which are related to an increase of the risk of suffering from a cardiovascular disease. However, the effect of VLDL on insulin resistance was unknown”, says Manuel Vázquez Carrera.
Results show that VLDL can cause an increase of insulin resistance, which precedes and predicts the development of type 2 diabetes. “These lipoproteins induce the process known as the endoplasmic reticulum stress, which favours inflammation and insulin resistance. We proved that the VLDL compound which favours these processes would be an apolipoprotein part of the VLDLs, the apo CIII”, says the researcher.
According to the researchers, this study shows the need to pay more attention to the increase of triglycerides in patients with diabetes, and it opens the door to designing more aggressive treatments in order to reduce those. “Given the situation that these results seem to pinpoint that triglycerides are another factor leading to insulin resistance and type 2 diabetes, a better control of VLDL-triglycerides could be a proper therapy to reduce the risk of suffering from this disease” says Manuel Vázquez.
“The next goal for the group is to prove in patients that this strategy which aims to reduce aggressively the triglycerides can delay or prevent the development of insulin resistance and type 2 diabetes” concludes the researcher.
G. Botteri, M. Montori, A. Gumà, J. Pizarro, L. Cedó, J.C. Escolà-Gil, D. Li, E. Barroso, X. Palomer, A.B. Kohan, M. Vázquez-Carrera. “VLDL and apolipoprotein CIII induce ER stress and inflammation and attenuate insulin signalling via Toll-like receptor 2 in mouse skeletal muscle cells”. Diabetologia, August 2017. Doi: https://doi.org/10.1007/s00125-017-4401-5
Universitat de Barcelona