Lalic 2109 MiP2019
Lalic NM, Krako Jakovljevic N, Pavlovic K, Zujovic T, Lukic LJ, Milicic T, Lalic K, Jotic A (2019)
Pathogenesis and future natural course of type 2 diabetes mellitus (T2DM) is a result of an interplay between many mechanisms, which affect many target organs. Among these mechanisms, the impairment of β-cell function and a decrease of insulin sensitivity on the level of liver and muscle cells appear to play a major role. Insulin resistance (IR) is one of the basic pathophysiological mechanisms in T2DM, which accounts for 90-95% of all diabetes cases. In the state of insulin resistance, insulin sensitivity is lowered, which leads to an inadequate response of peripheral tissues to insulin (skeletal muscle, adipose tissue and liver).
Mitochondrial dysfunction is a characteristic metabolic defect in people with T2DM and nondiabetic obese individuals. There is a certain controversy in whether mitochondrial dysfunction is a cause or a consequence of insulin resistance.In eather case, whether this is a primary or an acquired defect it is present and needs to be confronted. We need drugs that will improve mitochondrial dysfunction in multiple organs, and in this way have the potential to improve insulin sensitivity in both muscle and liver and improve β-cell function.
Our group investigates different aspects of insulin resistance. In human studies we use the clamp technique and minimal model approaches. More recently, we established in vitro IR models on muscle and liver cell lines in which we induce IR ether by chronic insulin or chronic palmitate treatments, to study both aspects of IR pathogenesis (disturbed insulin pathway and lipotoxicity). In those models we study mitochondrial function in depth by using high resolution respirometry. Our in vitro IR models will allow us to test potential therapeutics and how they affect mitochondrial function. We believe, that a promising therapeutic strategy in treating T2DM would be to target defects in mitochondrial function aiming to simultaneously improve both insulin secretion and insulin sensitivity at various levels.
• Bioblast editor: Plangger M, Tindle-Solomon L • O2k-Network Lab: RS Belgrade Lalic NM
Labels: MiParea: Respiration Pathology: Diabetes
Tissue;cell: Skeletal muscle, Liver
- Clinic Endocrinology, Diabetes Metabolic Diseases, CCS, Fac Medicine, Univ Belgrade. – [email protected]