Isoleucine, a Blood Glucose-Lowering Amino Acid, Increases Glucose Uptake in Rat Skeletal Muscle in the Absence of Increases in AMP-Activated Protein Kinase Activity

• Published in: The Journal of nutrition Vol. 135; no. 9; pp. 2103 - 2108
• Main Authors: Doi, Masako, Yamaoka, Ippei, Nakayama, Mitsuo, Mochizuki, Shinji, Sugahara, Kunio, Yoshizawa, Fumiaki
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Elsevier Inc 01.09.2005; American Society for Nutritional Sciences; American Institute of Nutrition
• Subjects: Adenosine Diphosphate - metabolism; adenosine monophosphate; Adenosine Monophosphate - metabolism; Adenosine Triphosphate - metabolism; Amino acids; AMP-activated protein kinase; AMP-Activated Protein Kinases; Animals; Biochemistry; Biological and medical sciences; blood glucose; Blood Glucose - metabolism; carbohydrate metabolism; enzyme activity; Enzymes; Fatty Acids, Nonesterified - blood; Feeding. Feeding behavior; Fundamental and applied biological sciences. Psychology; Glucose; Glucose - metabolism; glycogen; Glycogen - biosynthesis; Hypoglycemic Agents - blood; Hypoglycemic Agents - pharmacology; insulin; Insulin - blood; insulin-independent glucose uptake; isoleucine; Isoleucine - blood; Isoleucine - pharmacology; leucine; Leucine - blood; Leucine - pharmacology; Male; Metabolism; Multienzyme Complexes - metabolism; muscle; Muscle, Skeletal - enzymology; Muscle, Skeletal - metabolism; Muscular system; oral administration; Osmolar Concentration; Protein Serine-Threonine Kinases - metabolism; Rats; Rats, Wistar; Rodents; skeletal muscle; Striated muscle. Tendons; tissue culture; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Vertebrates: osteoarticular system, musculoskeletal system; leucine; glucose; 2-[3H]DG; PKC; AMP-activated protein kinase; isoleucine; PI3K; 2DG; NEFA; muscle; 2-[3H]DGP; mTOR; AMPK; wt; Nutrition; Rat; Enzyme; Transferases; Rodentia; Glucose; Leucine; Striated muscle; Uptake; Blood; Vertebrata; Mammalia; Protein kinase; Aminoacid; Animal; Carbohydrate; Isoleucine
• ISSN: 0022-3166; 1541-6100
• DOI: 10.1093/jn/135.9.2103

Leucine and isoleucine were shown to stimulate insulin-independent glucose uptake in skeletal muscle cells in vitro. In this study, we examined the effects of leucine and isoleucine on blood glucose in food-deprived rats and on glucose metabolism in skeletal muscle in vivo. Furthermore, we investigated the possible involvement of the energy sensor, 5′-AMP-activated protein kinase (AMPK), in the modulation of glucose uptake in skeletal muscle, which is independent of insulin, and also in leucine- or isoleucine-stimulated glucose uptake. Oral administration of isoleucine, but not leucine, significantly decreased the plasma glucose concentration. An i.v. bolus of 2-[1,2-3H]-deoxyglucose (2-[3H]DG) was administered to calculate glucose uptake. Glucose uptake in the skeletal muscle did not differ after leucine administration, but glucose uptake in the muscles of rats administered isoleucine was 73% greater than in controls, suggesting that isoleucine increases skeletal muscle glucose uptake in vivo. On the contrary, in the skeletal muscles, administration of leucine but not isoleucine significantly increased [U-14C]-glucose incorporation into glycogen compared with controls. AMPK α1 activity in skeletal muscle was not affected by leucine or isoleucine administration. However, isoleucine, but not leucine, significantly decreased AMPK α2 activity. The decrease in AMPK α2 activity was thought to be due to decreases in AMP content and the AMP:ATP ratio, which were related to the isoleucine administration. This is the first report of isoleucine stimulating glucose uptake in rat skeletal muscle in vivo, and these results indicate that there might be a relation between the reduction in blood glucose and the increase in skeletal muscle glucose uptake that occur with isoleucine administration in rats. The alterations in glucose metabolism caused by isoleucine may result in an improvement of the availability of ATP in the absence of increases in AMP-activated protein kinase activity in skeletal muscle.