TY - BOOK

T1 - Regulation of Metabolic Signaling in Human Skeletal Muscle

T2 - Impact of Gastric Bypass, Insulin and Exercise in a Muscle Fiber Type Specific Perspective

AU - Albers, Peter Hjorth

N1 - CURIS 2014 NEXS 341

PY - 2014

Y1 - 2014

N2 - Regulation of glucose metabolism, despite intense research through decades, is still not clear. Skeletal muscle is highly important for maintaining glucose homeostasis. Regulation of skeletal muscle glucose metabolism is influenced by protein signaling and changes in the activity of metabolic enzymes. Skeletal muscle consists of thousands of muscle fibers. These fibers can roughly be classified into type I and type II muscle fibers. The overall aim of this PhD thesis was to investigate the effect of insulin and exercise on human muscle fiber type specific metabolic signaling. The importance of human type I muscle fibers is illustrated by the finding of a positive correlation between the relative distribution of type I fibers in the muscle and whole-body insulin sensitivity. This suggests, that type I muscle fibers are more insulin sensitive than type II muscle fibers. Improved insulin sensitivity in type I muscle fibers possibly reflects a superior effect of insulin on metabolic signaling compared to type II muscle fibers. This was investigated in the present thesis by examining muscle biopsies from lean and obese healthy subjects as well as patients with type 2 diabetes. From these muscle biopsies, single muscle fibers were dissected. Muscle fiber type determination was performed and fibers were pooled in groups of type I and II muscle fibers. Muscle fiber pools were investigated for regulation of signaling molecules and enzymes, involved in glucose metabolism. Irrespective of the group of subjects investigated, results suggest that the sensitivity to insulin to regulate these signaling proteins is similar in type I and II muscle fibers. On the other hand, abundance of metabolic enzymes is higher in type I compared to type II muscle fibers. This suggests, that type I muscle fibers have a higher glucose handling capacity compared to type II muscle fibers. To investigate whether regulation of proteins involved in glucose metabolism during an acute bout of exercise is muscle fiber type specific, muscle biopsies from young healthy men were taken. Subjects performed either continuous or interval exercise. Samples of type I and II muscle fibers were prepared as described above. Results indicate that the regulation of the metabolic protein AMP-activated protein kinase (AMPK) and downstream targets is similar in type I and II muscle fibers during continuous exercise. In contrasts, a decreased regulation of these proteins were evident in type I vs II muscle fibers during interval exercise. The overall conclusion is that metabolic signaling in type I and II muscle fibers in some cases are similar (during insulin stimulation or continuous exercise) and in other cases are different (during interval exercise). The abundance of signaling proteins and metabolic enzymes are in most cases different in type I and type II muscle fibers, indicating that their glucose metabolism is different.

AB - Regulation of glucose metabolism, despite intense research through decades, is still not clear. Skeletal muscle is highly important for maintaining glucose homeostasis. Regulation of skeletal muscle glucose metabolism is influenced by protein signaling and changes in the activity of metabolic enzymes. Skeletal muscle consists of thousands of muscle fibers. These fibers can roughly be classified into type I and type II muscle fibers. The overall aim of this PhD thesis was to investigate the effect of insulin and exercise on human muscle fiber type specific metabolic signaling. The importance of human type I muscle fibers is illustrated by the finding of a positive correlation between the relative distribution of type I fibers in the muscle and whole-body insulin sensitivity. This suggests, that type I muscle fibers are more insulin sensitive than type II muscle fibers. Improved insulin sensitivity in type I muscle fibers possibly reflects a superior effect of insulin on metabolic signaling compared to type II muscle fibers. This was investigated in the present thesis by examining muscle biopsies from lean and obese healthy subjects as well as patients with type 2 diabetes. From these muscle biopsies, single muscle fibers were dissected. Muscle fiber type determination was performed and fibers were pooled in groups of type I and II muscle fibers. Muscle fiber pools were investigated for regulation of signaling molecules and enzymes, involved in glucose metabolism. Irrespective of the group of subjects investigated, results suggest that the sensitivity to insulin to regulate these signaling proteins is similar in type I and II muscle fibers. On the other hand, abundance of metabolic enzymes is higher in type I compared to type II muscle fibers. This suggests, that type I muscle fibers have a higher glucose handling capacity compared to type II muscle fibers. To investigate whether regulation of proteins involved in glucose metabolism during an acute bout of exercise is muscle fiber type specific, muscle biopsies from young healthy men were taken. Subjects performed either continuous or interval exercise. Samples of type I and II muscle fibers were prepared as described above. Results indicate that the regulation of the metabolic protein AMP-activated protein kinase (AMPK) and downstream targets is similar in type I and II muscle fibers during continuous exercise. In contrasts, a decreased regulation of these proteins were evident in type I vs II muscle fibers during interval exercise. The overall conclusion is that metabolic signaling in type I and II muscle fibers in some cases are similar (during insulin stimulation or continuous exercise) and in other cases are different (during interval exercise). The abundance of signaling proteins and metabolic enzymes are in most cases different in type I and type II muscle fibers, indicating that their glucose metabolism is different.

UR - https://soeg.kb.dk/permalink/45KBDK_KGL/fbp0ps/alma99122050170605763

M3 - Ph.D. thesis

BT - Regulation of Metabolic Signaling in Human Skeletal Muscle

PB - Department of Nutrition, Exercise and Sports, Faculty of Science, University of Copenhagen

CY - Copenhagen

ER -