Study: New signaling pathway increases glucose uptake in skeletal muscle
A novel protein called sucrose nonfermenting AMPK-related kinase (SNARK) involved in mediating glucose transport has been found to be activated in skeletal muscle in response to contraction and exercise in both rodents and humans, according to a study published Aug. 16 in Proceedings of the National Academy of Sciences.
The research was conducted by scientists from the department of exercise and sport sciences, University of Copenhagen, Denmark in collaboration with scientists at the Joslin Diabetes Center at Harvard Medical School in Boston and Research Center for Innovative Oncology, National Cancer Center Hospital East in Chiba, Japan.
The signaling mechanisms that mediate the important effects of contraction to increase glucose transport in skeletal muscle are not well understood, but are known to occur through an insulin-independent mechanism, according to Ho-Jin Koh, PhD, instructor in medicine at Joslin, and colleagues.
For individuals in which insulin only has little effect (insulin resistance), the contraction-induced pathway represents an alternative pathway to increase glucose uptake and an alternative signaling pathway for pharmacological intervention in regulating glucose homeostasis for pharmaceutical companies.
The researchers used transgenic animal models and showed that by over-expressing an inactive mutant of SNARK in mouse skeletal muscle, contraction-induced glucose uptake was severely blunted by 40 to 50 percent compared with control animals.
The data in this study clearly support a role for SNARK in regulating glucose transport during muscle contraction and exercise, but it also strongly suggests that multiple or redundant signals may mediate the effects of contraction on activating glucose transport, noted Koh and colleagues.
In future studies it will be important to understand the mechanism of SNARK activation in vivo, as well as explore the possibility that SNARK mediates other aspects of metabolism in skeletal muscle, concluded the authors.
The research was conducted by scientists from the department of exercise and sport sciences, University of Copenhagen, Denmark in collaboration with scientists at the Joslin Diabetes Center at Harvard Medical School in Boston and Research Center for Innovative Oncology, National Cancer Center Hospital East in Chiba, Japan.
The signaling mechanisms that mediate the important effects of contraction to increase glucose transport in skeletal muscle are not well understood, but are known to occur through an insulin-independent mechanism, according to Ho-Jin Koh, PhD, instructor in medicine at Joslin, and colleagues.
For individuals in which insulin only has little effect (insulin resistance), the contraction-induced pathway represents an alternative pathway to increase glucose uptake and an alternative signaling pathway for pharmacological intervention in regulating glucose homeostasis for pharmaceutical companies.
The researchers used transgenic animal models and showed that by over-expressing an inactive mutant of SNARK in mouse skeletal muscle, contraction-induced glucose uptake was severely blunted by 40 to 50 percent compared with control animals.
The data in this study clearly support a role for SNARK in regulating glucose transport during muscle contraction and exercise, but it also strongly suggests that multiple or redundant signals may mediate the effects of contraction on activating glucose transport, noted Koh and colleagues.
In future studies it will be important to understand the mechanism of SNARK activation in vivo, as well as explore the possibility that SNARK mediates other aspects of metabolism in skeletal muscle, concluded the authors.