Mitochondrial Utilization of Competing Fuels Is Altered in Insulin Resistant Skeletal Muscle of Non-obese Rats (Goto-Kakizaki).

摘要: Aim: Insulin-resistant skeletal muscle is characterized by metabolic inflexibility with associated alterations in substrate selection, mediated peroxisome-proliferator activated receptor delta (PPARdelta. Although it established that PPARdelta contributes to the alteration of energy metabolism, not clear whether plays a role mitochondrial fuel competition. While nutrient overload may impair flexibility congestion within mitochondria, absence obesity defects at level have yet been excluded. We sought determine reduced PPAR content insulin-resistant rat non-obese model T2DM (Goto-Kakizaki, GK) ameliorate inhibitory effect fatty acid (i.e. palmitoylcarnitine) on carbohydrate oxidization pyruvate) fibers. Methods: Bioenergetic function was oxidative soleus (S) and glycolytic white gastrocnemius (WG) muscles measurement respiration rates permeabilized fibers presence complex I, II, IV substrates. Mitochondrial measured citrate synthase (CS) succinate dehydrogenase activity (SDH). Western blot used protein expression PPARdelta, PDK isoform 2 4. Results: CS SDH activity, key markers content, were ~10-30% diabetic vs control, evident both muscles. PPARdelta(p<0.01), PDK2 (p<0.01), PDK4 (p=0.06) GK animals compared Wistar rats (N=6 per group). Ex vivo determined substrates, suggested unaltered bioenergetic muscle. Respiration pyruvate higher palmitoylcarnitine animal groups fiber types. Moreover, 25±6% (S), 37±6% 63±6% 57±8% for controls GK, respectively. The significantly greater than (p<10-3). Conclusion: With competing fuels, acids diminishes mitochondria ability utilize derived substrates despite content.