Glucose, exercise and insulin: emerging concepts

Abstract

Physical exercise induces a rapid increase in the rate of glucose uptake in the contracting skeletal muscles. The enhanced membrane glucose transport capacity is caused by a recruitment of glucose transporters (GLUT4) to the sarcolemma and t-tubules. This review summarises the recent progress in the understanding of signals that trigger GLUT4 translocation in contracting muscle. The possible involvement of calcium, protein kinase C (PKC), nitric oxide (NO), glycogen and AMP-activated protein kinase (AMPK) are discussed. Furthermore, the possible mechanisms behind the well-described improvement of insulin action on glucose uptake and glycogen synthase activity in the post-exercise period is discussed. It is concluded that both during and following muscle contractions, glycogen emerges as an important modulator of signalling events in glucose metabolism.

Figure 1. Glycogen content (A) and GLUT4 cell surface content (B) in plantaris muscles at rest (▪) and after contractions (□)

Rats were pre-treated by swimming and diet to obtain muscles with high (HG), normal (NG) or low (LG) glycogen content. Hindlimbs were perfused and the calf muscles of one leg were electrically stimulated (100 ms trains with 2 s intervals) for 10 min. Plantaris muscles were dissected out of the rested and electrically stimulated leg and were incubated in 2-N-4-(1-azi-2,2,2,-trifluoroethyl)benzoyl-1,3-bis(d-mannose-4-yloxy)-2-propylamide (ATB-BMPA) to label cell surface GLUT4. Data are presented as means ±s.e.m. (n = 5-8). * Different from HG (P < 0.05). ‡ Different from NG (P < 0.05). Figure is adapted from Derave et al. (1999) with permission.

Figure 2. Additive effect of contractions and hypoxia on glucose uptake in perfused rat hindquarters

Glucose uptake was measured at rest and after 60 min of hypoxia (n = 17). Thereafter, hypoxic perfusion was either continued for another 30 min (continuous line and filled symbol, n = 3) or a 5 min electrical stimulation was started (dotted line and open symbol, n = 14). Values are means ±s.e.m.* P < 0.05 compared with 60 min of hypoxia. Data are reproduced from Derave & Hespel (1999) with permission.

Figure 3. Correlation between the degree of glycogen depletion and the insulin-stimulated glucose uptake in thigh muscles of healthy men

Subjects performed 60 min one-legged knee-extensor exercise and glycogen depletion was measured as the difference in glycogen content between the rested and exercised leg 3-4 h following exercise. The insulin-stimulated glucose uptake was measured as the area under the curve (AUC) after baseline subtraction for glucose uptake (A-V difference × flow) in the exercised leg during a 120 min hyperinsulinaemic (∼100 μu ml⁻¹) euglycaemic clamp starting 3-4 h post-exercise. n = 14 and r²= 0.53. Data are combined from Wojtaszewski et al. (1997) and Wojtaszewski et al. (2000a).

Figure 4. Correlations between the post-exercise glycogen content and the increase in muscle glycogen content (A) and muscle glycogen synthase activity (B) in response to food intake in healthy men

Subjects performed either a high (75 % ) or a low (50 % ) intensity exercise bout on a bicycle ergometer. After 3 h of rest a carbohydrate rich meal was taken, and the subjects rested for another 3 h. Biopsies from vastus lateralis 3 h after exercise (before food intake) and 3 h after food intake were analysed for glycogen content and glycogen synthase activity (n = 13). Data are reproduced from Wojtaszewski et al. (2001) with permission.