Jelenik 2014 Diabetes
|Jelenik T, Séquaris G, Kaul K, Ouwens DM, Phielix E, Kotzka J, Knebel B, Weiß J, Reinbeck AL, Janke L, Nowotny P, Partke HJ, Zhang D, Shulman GI, Szendroedi J, Roden M (2014) Tissue-specific differences in the development of insulin resistance in a mouse model for type 1 diabetes. Diabetes 63:3856-67.|
Abstract: While insulin resistance is known to underlie type 2 diabetes, its role in the development of type 1 diabetes is gaining increasing interest more recently. In a model of type 1 diabetes, the non-obese diabetic (NOD) mouse, we found that insulin resistance driven by lipid- and glucose-independent mechanisms is already present in liver of pre-diabetic mice. Hepatic insulin resistance is associated with a transient rise in mitochondrial respiration, followed by increased production of lipid peroxides and c-jun N-terminal kinase (JNK) activity. At the onset of diabetes, increased adipose tissue lipolysis promotes myocellular diacylglycerol accumulation. This is paralleled by increased myocellular protein kinase C theta (PKCθ) activity and serum fetuin A levels. Muscle mitochondrial oxidative capacity is unchanged at the onset, but decreases at later stages of diabetes. In conclusion, hepatic and muscle insulin resistance manifest at different stages and involve distinct cellular mechanisms during the development of diabetes in the NOD mouse.
• Keywords: DE Duesseldorf Roden M
• O2k-Network Lab: DE Duesseldorf Roden M
Labels: MiParea: Respiration Pathology: Diabetes
Organism: Mouse Tissue;cell: Skeletal muscle, Liver Preparation: Permeabilized tissue, Isolated mitochondria
Coupling state: OXPHOS, ET Pathway: N, NS, ROX HRR: Oxygraph-2k