Effect of intraperitoneal injection of glucose on glucose oxidation and energy expenditure in the mdx mouse model of Duchenne muscular dystrophy

Abstract

Previous studies suggesting that glucose metabolism could be impaired in the skeletal muscles of the mdx mouse led us to study the metabolic response to i.p. injection of either glucose or glucose and insulin in the free-moving mdx mouse. In the first study, changes in blood glucose and plasma insulin levels were measured in mice with chronic venous cannulae. In the second study, the thermogenic response to glucose and the changes induced on glucose oxidation (Gox) and lipid oxidation (Lox) were assessed by indirect calorimetry. The experiments showed that insulin response, as well as whole body glucose uptake, were normal in mdx mice. Addition of exogenous insulin abolished the increase in blood glucose level similarly in mdx and control mice. The thermogenic response to glucose was identical in mdx and control mice but, when insulin was injected with glucose, it increased significantly in mdx mice. Exogenous glucose increased Gox less and decreased Lox less in mdx than in control mice. Addition of exogenous insulin reduced the difference between mdx and control mice but affected Gox and Lox less in mdx than in control mice. Key words Duchenne muscular dystrophy middle dot mdx Mouse middle dot Glucose tolerance test middle dot Respiratory quotient middle dot Energy metabolism middle dot Indirect calorimetry

DOCK3 is a dosage-sensitive regulator of skeletal muscle and Duchenne muscular dystrophy-associated pathologies

“…Dock3 KO mice demonstrated significantly decreased distance traveled and average velocity compared to WT mice, indicating an overall reduction in basal locomotor function (Figures 5E, 5F, Supplemental Figure 2). This demonstrates an overall decrease in locomotor ability in Dock3 KO mice at 6 months of age similar to that reported for the mdx mouse model and consistent with our findings that Dock3 KO mice have significant muscle weakness and myofiber atrophy 33,34 , [35][36][37][38][39][40] . Additionally, we assessed cardiac function in WT and Dock3 KO mice and found no significant differences in functional parameters (Supplemental Figure 3).…”

Hypoxia on Hippocampal Slices from Mice Deficient in Dystrophin (mdx) and Isoforms (mdx3cv)

“…A curious feature was the higher incidence of tEPSP recoveries in slices from mdx mutants than in slices from control and mdx3cv mice. This suggests that mdx slices may be more resistant to damage by repeated energy deprivation-in other words, that protection by precon ditoning is more effective-perhaps because of disturbed metabolism in mdx mice (Vignos and Lefkowitz, 1959;Mokhtarian and Even, 1996;Tracey et aI., 1996). If this compensating mechanism operates at the linkage be tween membrane cytoskeleton and extracellular glyco proteins, for which the C-terminal 70-kDa isoform is crucial (Lederfein et aI., 1992;Cox et aI., 1993;Ohlen dieck, 1996), it may be absent in slices from mdx3cv mice that lack the 70-kDa and other isoforms.…”

“…Hip pocampal slices were taken at random from one of the three groups, wild-type C57 (control) mice, mdx mutants, or mdx3cv mutants (Table 1). Because dystrophy is asso ciated with impaired brain metabolism (Tracey et aI., 1996)-possibly including disturbed glycolysis (Vignos and Lefkowitz, 1959;Lilling and Beitner, 1991;Even et aI., 1994;Mokhtarian and Even, 1996)-experiments were done on slices maintained in standard medium (containing 10 mmollL glucose) and in medium contain ing only 4 mmollL glucose, in which synaptic responses are more susceptible to irreversible effects of hypoxia (Schurr et aI., 1987;Roberts and Sick, 1992;Zhu and Kmjevic, 1998). A preliminary report of these results has appeared as an abstract (Godfraind et aI., 1998).…”

Regeneration and myogenic cell proliferation correlate with taurine levels in dystrophin- and MyoD-Deficient muscles

“…Additional metabolites were altered in mdx diaphragm but not in the TA muscle, and this likely was due to the greater involvement of the diaphragm in dystrophy. Lower levels of alanine, glutamate, and succinate in mdx compared with normal diaphragm extracts may be further demonstration of decreased oxidative use of glucose and free fatty acids during damage (Decrouy et al, 1993;Even et al, 1994;Mokhatarian and Even, 1996) or secondary to the decreased muscle:nonmuscle mass in the mdx diaphragm (Stedman et al, 1991;.…”