title: Non-oxidative glucose disposal is reduced in type 2 diabetes, but can be restored by aerobic exercise.
abstract: Whole-body glucose utilization consists of mitochondrial glucose oxidation and non-oxidative glycogen synthesis. We examined whether reduction of both non-oxidative glucose disposal and glucose oxidation contributes to insulin resistance in type 2 diabetes. We also examined the effects of exercise on these two components. Whole-body glucose disposal rate (GDR, mg/kg/min) was evaluated in 37 type 2 diabetic (T2DM) and 17 non-diabetic (non-DM) subjects as the mean of glucose infusion rate during steady state in the euglycaemic-hyperinsulinaemic clamp study. Glucose oxidation rates were assessed by indirect calorimetry, and non-oxidative GDR was calculated by subtracting glucose oxidation rate from GDR. Intramyocellular lipid (IMCL) content of the soleus muscle was measured using (1)H-magnetic resonance spectroscopy. In 10 T2DM subjects, the changes in oxidative and non-oxidative glucose disposal during clamp were examined after 3-month exercise intervention. GDR (2.93 +/- 1.55 vs. 4.55 +/- 1.83, p = 0.001) and non-oxidative GDR (1.45 +/- 1.52 vs. 3.01 +/- 1.87, p = 0.002) were significantly lower in T2DM than in non-DM subjects. Glucose oxidation rate was comparable in the two groups, and inversely correlated with IMCL (n = 15, r =-0.565, p = 0.028). GDR (2.28 +/- 1.67 to 4.63 +/- 2.42, p = 0.021) and non-oxidative GDR (0.72 +/- 1.27 to 2.26 +/- 1.91, p = 0.047) were increased after exercise intervention, although the change in glucose oxidation rate was not significant. In summary, reduction of non-oxidative glucose disposal may contribute to decreased whole-body glucose utilization. In addition, exercise improves insulin resistance mainly by increasing non-oxidative glucose disposal in type 2 diabetes.
authors.affiliation: Department of Metabolism, Endocrinology, and Molecular Medicine, Osaka City University Graduate School of Medicine, Osaka, Japan. yock@med.osaka-cu.ac.jp
authors.forename: H
authors.initials: H
authors.lastname: Yokoyama
authors.forename: K
authors.initials: K
authors.lastname: Mori
authors.forename: M
authors.initials: M
authors.lastname: Emoto
authors.forename: T
authors.initials: T
authors.lastname: Araki
authors.forename: M
authors.initials: M
authors.lastname: Teramura
authors.forename: K
authors.initials: K
authors.lastname: Mochizuki
authors.forename: T
authors.initials: T
authors.lastname: Tashiro
authors.forename: K
authors.initials: K
authors.lastname: Motozuka
authors.forename: Y
authors.initials: Y
authors.lastname: Inoue
authors.forename: Y
authors.initials: Y
authors.lastname: Nishizawa
mesh_terms: D000328:Adult; D000368:Aged; D000886:Anthropometry / Q000379:methods; D001786:Blood Glucose / Q000378:metabolism; D002153:Calorimetry, Indirect / Q000379:methods; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000378:metabolism* / Q000534:rehabilitation*; D015444:Exercise; D005260:Female; D015309:Glucose Clamp Technique; D006801:Humans; D007333:Insulin Resistance; D050356:Lipid Metabolism; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000378:metabolism; D010084:Oxidation-Reduction
chemical_list: D001786:Blood Glucose