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Pathogenesis and consequent natural course of type 2 diabetes (T2D) is a result of interplay between many mechanisms, which affect many target organs. Among these mechanisms,the impairment of β-cell function and a decrease of insulin sensitivity, i.e. insulin resistance (IR) on the level of liver and muscle cells appear to play a major role. Mitochondrial dysfunction (MD) is a metabolic defect detected both in people with T2D and nondiabetic obese individuals. Recent studies have shown that MD might be a predisposing factor for ectopic lipid deposition and IR. Other data have shown a strong relationship between MD and IR, especially in insulin-responsive tissues, e.g skeletal muscle and liver, but also on the whole body level. In order to try to elucidate more this relationship, we compared the changes of mitochondrial function both in muscle and liver cell lines, evaluated by using high resolution respirometry, in two different models, palmitate-induced and hyperinsulinemia-induced models of IR (inhibition of Akt phosphorylation), the latter being more similar to the IR in human settings. We found that chronic hyperinsulinemia was able to decrease respiratory acceptor control ratio only in the muscle and not in the hepatic cell line, while there was no effect on mitochondrial respiration comparable to the palmitate treatment. Altogether, the relationship between impaired MD, IR and T2D might be both disease and tissue specific. Based on the findings from the studies of MD, some agents are under investigation which might modulate the course of IR and T2D targeting mitochondrial function. The data from previous studies, including ours, suggest that these therapeutic agents should be not only MD but also tissue-specific.
Nebojša M. Lalić (1958), MD, PhD, FRCP, is currently Professor of Internal Medicine at the Faculty of Medicine, University of Belgrade as well as Director and Head of the Department for Metabolic Disorders, Intensive Treatment and Cell Therapy in Diabetes, Clinic for Endocrinology, Diabetes and Metabolic Diseases, Clinical Center of Serbia in Belgrade.
Nebojsa Lalic graduated in 1982 at Faculty of Medicine in Belgrade where he completed residency in Internal medicine in 1990, as well as his PhD thesis in 1993. In 1991, he was a visiting scientist at the Clinical Research Section and Immunology Section, Joslin Diabetes Center, Boston, USA. The principal interest of Dr Lalic scientific work in diabetology/endocrinology has been concentrated on the relationship between insulin secretion and insulin sensitivity impairments in Type 2 diabetes, their relevance for the pathogenesis of diabetes and its late complications and the possibilities of their therapeutic modulation (especially insulin pump treatment). In this context, he is also intensively involved in the metabolic studies of the possibilities of early detection and prevention of Type 2 diabetes, as well as of the late diabetic complications and comorbidities, especially coronary heart disease, ischemic stroke and neurodegenerative disorders. Dr Lalic has been involved in more than 200 papers in extenso in international journals, chapters, monographies and textbooks. He has been an investigator in several national and international projects, reviewer at many international meetings or journals.
From 1994 Dr Lalic has actively participated in the work of EGIR Study group, he has been involved in EGIR RISC project and he served twice in the Board of the EGIR Study group.
Dr Lalic has been Chair of the national expert committee for diabetes from 2002. Moreover, he is member in several national and international medical associations and societies. Until now he chaired organizing committee of three EASD Postgraduate Courses in Belgrade. Also, he is Chair Elect of the IDF Europe.
From 2012 he is the Dean of the Faculty of Medicine University of Belgrade. In addition, he has been elected for corresponding member in 2006 and for the full member of the Serbian Academy of Sciences and Arts in 2012.