GLUT11, but not GLUT8 or GLUT12, is expressed in human skeletal muscle in a fibre type-specific pattern

Abstract

Nine novel sugar transporter-like proteins have been discovered in the past 5 years. The mRNA for three of these, the glucose transporters (GLUT) GLUT8, GLUT11 and GLUT12, have been detected in human skeletal muscle. In the present study, we examined the pattern of expression and localization of the GLUT isoforms 8, 11 and 12 in human skeletal muscle using an immunohistochemical approach. Biopsies of human skeletal muscle from sedentary or trained healthy adults, from fetal muscle (24 weeks of gestation), from obese type-2 diabetic subjects, and from patients suffering from polymyositis or amyotrophic lateral sclerosis (ALS) were studied. GLUT8 and 12 immunoreactivity was below detection level in both developing and adult muscle fibres. GLUT11 immunoreactivity, however, was present in slow-twitch muscle fibres, but not in fast twitch fibres. Since, in contrast, GLUT4 was expressed in all investigated muscle fibres, the pattern of expression of GLUT11 differs from that of GLUT4, suggesting a specialized function for GLUT11 with a regulation independent from that of GLUT4. Obesity, type-2 diabetes, training, conditions of de- and reinnervation (ALS) and regeneration (polymyositis) failed to induce GLUT8 or -12 expression. Likewise, the fibre type-dependent pattern of GLUT11 immunoreactivity was unaltered. However, some slow muscle fibres lose their GLUT11 immunoreactivity under regeneration. Our results indicate that GLUT11 immunoreactivity, in contrast to that of GLUT4, is expressed exclusively in slow-twitch muscle fibres and is unaffected by physiological and pathophysiological conditions except in primary myopathy. GLUT8 and GLUT12 do not appear to be of importance in human muscle under physiological and pathophysiological conditions.

The protein family of glucose transport facilitators: It's not only about glucose after all

“…Endogenous GLUT11 protein was localized in heart and skeletal muscle with an antibody raised against the C-terminus of GLUT11 that does not distinguish between the different variants (117). Human GLUT11 is expressed exclusively in slow-twitch muscle fibers and is unaffected by physiological and pathophysiological conditions except in primary myopathy (117). Surprisingly, the human SLC2A11 gene has not orthologue in the rat and mouse genome (101).…”

“…Mutational analysis of the DSV motif in GLUT11 that corresponds to the ''fructose'' transporter motif ''NAI'' showed that also in GLUT11 this particular region of helix 7 determines substrate selectivity of the transporter (13). Endogenous GLUT11 protein was localized in heart and skeletal muscle with an antibody raised against the C-terminus of GLUT11 that does not distinguish between the different variants (117). Human GLUT11 is expressed exclusively in slow-twitch muscle fibers and is unaffected by physiological and pathophysiological conditions except in primary myopathy (117).…”

Fiber Types in Mammalian Skeletal Muscles

“…While the insulin-dependent transporter GLUT4 is continuously expressed from fetal life through mature adult muscle, GLUT1 and GLUT3 are found in fetal muscle but disappear around birth and are reexpressed only in regenerating fibers (256,257). Recently, expression of GLUT11 has been demonstrated in slow-twitch fibers, where it seems to be associated more with intracellular structures than to sarcolemma (258). This pattern of localization is strikingly different from that of GLUT4, which is associated almost exclusively with the plasma membrane in all fiber types (520).…”

Training-induced changes in membrane transport proteins of human skeletal muscle

“…GLUT5, also a member of the same transporter family, is a fructose transporter that seems to be insensitive to training (Hundal et al 1998). The less-frequently studied GLUT11 is unaffected by training (Gaster et al 2004). …”