Non-Insulin and Non-Exercise Related Increase of Glucose Utilization in Rats and Mice.

Abstract

The effects of high-energy phosphate contents in muscles on glucose tolerance and glucose uptake into tissues were studied in rats and mice. Enhanced glucose tolerance associated with depleted high-energy phosphates and elevated glycogen content in muscles and liver was observed in animals fed creatine analogue beta-guanidinopropionic acid (beta-GPA). Distribution of infused 2-[1-14C]deoxy-D-glucose in tissues especially in the soleus muscle, kidney, and brain was greater in mice fed beta-GPA than controls. The glucose uptake was decreased when the contents of ATP and glycogen were normalized following creatine supplementation. Plasma insulin in animals at rest was lower and its concentration after intraperitoneal glucose infusion tended to be less in animals fed beta-GPA than controls (p > 0.05), although the pattern of insulin response to glucose loading was similar to the control. The daily voluntary activity in beta-GPA fed mice was also less than controls. These results suggest that improved glucose tolerance is not related to elevated insulin concentration and/or decreased glycogen following exercise. Such improvement may be due to an increased mitochondrial energy metabolism caused by depletion of high-energy phosphates.

Metabolic Modulation of Muscle Fiber Properties Unrelated to Mechanical Stimuli

“…This tendency for an increase in the mitochondrial enzyme activity of single muscle fibers, combined with an increase in the percentage of slow fibers, is consistent with the enzymatic adaptations seen in whole homogenates of both predominantly fast and predominantly slow muscles [11,14,16,18,21]. Although the activities of most of the glycolytic enzymes are reduced in these muscles [18,21], resting glucose uptake [34] and GLUT-4 glucose transporter expression [18] are increased. Hexokinase activity also is elevated in ␤-GPA-fed rats [21].…”

The Effect of the Creatine Analogue Beta-guanidinopropionic Acid on Energy Metabolism: A Systematic Review

“…Included studies showed decreased creatine, phosphocreatine, total creatine (creatine+phosphocreatine), and ATP levels of respectively 66.1% (SD 19.2), 79.7% (SD 21.6), 86.7% (SD 10.0), and 38.8% (SD 13.6) after ßGPA (Figure 3 and Figure S1) [11], [12], [20], [22], [25], [31]–[33], [36], [37], [40], [43], [44], [48]–[51], [53], [54], [56], [57], [62]–[73]. We excluded one study with conflicting results (unchanged creatine, as well as a 56% increase) [71].…”

Decreasing intramuscular phosphagen content simultaneously increases plasma membrane FAT/CD36 and GLUT4 transporter abundance

“…Body mass was monitored two times weekly. ␤-GPA was supplemented daily to the diet as described in previous studies (11,21,26,27). Animals were fasted overnight and anaesthetized with an intraperitoneal injection of pentobarbital sodium (5 mg/100 g body mass) before all experimental procedures.…”

“…Increased muscle GLUT4 mRNA and total protein content have been reported in response to ␤-GPA feeding (23,36), and improved insulin-stimulated glucose uptake/clearance in rodent skeletal muscle following ␤-GPA feeding has also been observed (20,21,23). However, there has been no specific assessment of changes in plasma membrane GLUT4 content, which is physiologically more relevant to the process of glucose transport.…”