Effects of high-fat diet and exercise training on intracellular glucose metabolism in rats

Abstract

We examined the effects of high-fat diet (HFD) and exercise training on insulin-stimulated whole body glucose fluxes and several key steps of glucose metabolism in skeletal muscle. Rats were maintained for 3 wk on either low-fat (LFD) or high-fat diet with or without exercise training (swimming for 3 h per day). After the 3-wk diet/exercise treatments, animals underwent hyperinsulinemic euglycemic clamp experiments for measurements of insulin-stimulated whole body glucose fluxes. In addition, muscle samples were taken at the end of the clamps for measurements of glucose 6-phosphate (G-6-P) and GLUT-4 protein contents, hexokinase, and glycogen synthase (GS) activities. Insulin-stimulated glucose uptake was decreased by HFD and increased by exercise training (P < 0.01 for both). The opposite effects of HFD and exercise training on insulin-stimulated glucose uptake were associated with similar increases in muscle G-6-P levels (P < 0.05 for both). However, the increase in G-6-P level was accompanied by decreased GS activity without changes in GLUT-4 protein content and hexokinase activities in the HFD group. In contrast, the increase in G-6-P level in the exercise-trained group was accompanied by increased GLUT-4 protein content and hexokinase II (cytosolic) and GS activities. These results suggest that HFD and exercise training affect insulin sensitivity by acting predominantly on different steps of intracellular glucose metabolism. High-fat feeding appears to induce insulin resistance by affecting predominantly steps distal to G-6-P (e.g., glycolysis and glycogen synthesis). Exercise training affected multiple steps of glucose metabolism both proximal and distal to G-6-P. However, increased muscle G-6-P levels in the face of increased glucose metabolic fluxes suggest that the effect of exercise training is quantitatively more prominent on the steps proximal to G-6-P (i.e., glucose transport and phosphorylation).

Assessment of the Antidiabetic Potential of an Aqueous Extract of Honeybush (Cyclopia intermedia) in Streptozotocin and Obese Insulin Resistant Wistar Rats

“…Feeding rats a high fat diet induces a state of insulin resistance associated with impaired insulin-stimulated glycolysis and glycogen synthesis (Kim et al, 2000). The STZ-induced diabetic rat model, following pancreatic -cell destruction and resulting in insulin deficiency rather than insulin resistance (OBIR model), was used to establish the optimal acute glucose lowering dose of a C. intermedia extract.…”

Peroxisome Proliferator-Activated Receptor (PPAR)-α Activation Prevents Diabetes in OLETF Rats

“…Experimental protocols. At 18 weeks of age, animals were prepared for glucose clamp experiments as previously described (18,19). Six hours before the clamps (7:00 A.M.), food was removed from the cage and catheters were placed.…”

Efeito da dieta hiperlipídica e do treinamento aeróbico na aterosclerose em camundongos apoE-/-

“…Porém, estes mesmos dois fatores atuam de maneira oposta com relação ao metabolismo de carboidratos. O treinamento físico aumenta o conteúdo de glicogênio estocado enquanto que a dieta hiperlipídica tem sido associada com diminuição na taxa de glicólise e na síntese de glicogênio 18 . Em relação ao aumento do A% nos grupos exercitados, sugere-se que o treinamento preservou a massa corporal magra (MCM), como pode ser constatada pela meta-análise realizada por Garrow e Summerbell 19 .…”