Lai 2014 Abstract2 MiP2014

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Bioenergetic differences between permeabilized red and white fibers of a non-obese model of type II diabetes.
Lai N
Mitochondr Physiol Network 19.13 - MiP2014

Lai N, Kummitha C, Cabras S, Martis A, Hoppel CL (2014)

Event: MiP2014

The cause and effect relationship between mitochondrial dysfunction and insulin resistance (IR) is still under debate. It appears that lipid accumulation is the principal cause of IR, while the mechanisms leading to fat accumulation in skeletal muscle are not clear yet [4]. The reduced mitochondrial content, β-oxidation impairment or fat overload could contribute to the lipid imbalance in the obese population [1,2,4]. Furthermore, evidence has been provided for metabolic alterations in the skeletal muscle of insulin resistant non-obese patients. In particular, in vivo ATP synthesis in the skeletal muscle of young, lean, insulin resistant offspring of type 2 diabetes mellitus (T2DM) patients was 30% lower than that in control subjects [5]. Both T2DM and physical inactivity cause functional adaptations in skeletal muscle, in which IR is reflected in higher ratios of glycolytic to oxidative capacities [7]. Thus, a study on fructose-induced insulin resistant rats revealed differences in energy metabolism between oxidative and glycolytic fibers; mitochondrial function is preserved in oxidative fibers (e.g. Type I) whereas β-oxidation is impaired in glycolytic fibers (e.g. Type II) [8].

We used a spontaneous non-obese model of T2DM, the Goto Kakizaki (GK) rat, to study the relationship between IR and mitochondrial bioenergetics. Age-matched (18 weeks) Wistar (W) rats were used as control. We investigated skeletal muscle mitochondrial bioenergetics using permeabilized fibers of soleus and white gastrocnemius muscle. The permeabilization and respirometric measurements of the fiber were performed on fresh muscle samples according to the previously developed protocol [3]. Mitochondria content was determined by citrate synthase (CS) and succinate dehydrogenase (SDH) activities [6].

Respiration of soleus muscle fibers was similar in both W and GK rats for Complex I- and Complex II-linked substrates (Fig. 1). In contrast, respiration of white gastrocnemius fibers was lower in GK rats than in W rats, in the presence of Complex II substrate (Succinate, S). In both fiber types respiration in the presence of Complex IV substrate was lower in GK rats than in W rats. In soleus muscle, CS and SDH activities of GK rats (CS: 42.5±3.6, SDH 3.5±0.4 mU∙mg-1) tended to be lower than in W rats (CS: 46.3±1.9, SDH 4.3±0.4 mU∙mg-1, P<0.1). Similarly, in white gastrocnemius muscle, CS and SDH activities of GK rats (CS: 14.2±0.6, SDH 0.9±0.2 mU∙mg-1) were lower than those in W rats (CS: 17±1.9, SDH 1.3±0.3 mU∙mg-1, P<0.05).

Our results indicate that in absence of obesity, insulin resistance in skeletal muscle is related to a reduced mitochondrial content in both fibers types and to metabolic alterations only in type II fibers. Further studies are needed to investigate the relationship between IR and mitochondria biogenesis as well as the fibers contribution to substrate utilization during the progression of T2DM.

O2k-Network Lab: US OH Cleveland Hoppel CL, US OH Cleveland Lai N, US VA Norfolk Lai N

Labels: MiParea: Respiration, mt-Biogenesis;mt-density, Exercise physiology;nutrition;life style  Pathology: Diabetes, Obesity 

Organism: Rat  Tissue;cell: Skeletal muscle  Preparation: Permeabilized cells 

Regulation: Aerobic glycolysis, ATP production 

Pathway: N, S, CIV 

Event: C2, Poster  MiP2014 


1-Dep Biomed Engineering; 2-Dep Pediatrics; 3-Dep Pharmacology; 4-Center Mitochondrial Disease; 5-Dep Medicine, School Medicine; Case Western Reserve Univ Cleveland, Ohio, USA; 6-Dep Mechanical, Chem Material Engineering, Univ Cagliari, Sardinia, Italy. –

Figure 1

MiP2014 Lai Figure2.jpg


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