Tissue-specific differences in the development of insulin resistance in a mouse model for type 1 diabetes

T Jelenik, G Séquaris, K Kaul, DM Ouwens, E Phielix… - Diabetes, 2014 - Am Diabetes Assoc
T Jelenik, G Séquaris, K Kaul, DM Ouwens, E Phielix, J Kotzka, B Knebel, J Weiß…
Diabetes, 2014Am Diabetes Assoc
Although insulin resistance is known to underlie type 2 diabetes, its role in the development
of type 1 diabetes has been gaining increasing interest. In a model of type 1 diabetes, the
nonobese diabetic (NOD) mouse, we found that insulin resistance driven by lipid-and
glucose-independent mechanisms is already present in the liver of prediabetic 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 activity. At …
Although insulin resistance is known to underlie type 2 diabetes, its role in the development of type 1 diabetes has been gaining increasing interest. In a model of type 1 diabetes, the nonobese diabetic (NOD) mouse, we found that insulin resistance driven by lipid- and glucose-independent mechanisms is already present in the liver of prediabetic 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 activity. At the onset of diabetes, increased adipose tissue lipolysis promotes myocellular diacylglycerol accumulation. This is paralleled by increased myocellular protein kinase C θ 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.
Am Diabetes Assoc