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Decreased hexosamine biosynthesis in GH-deficient dwarf rat muscle. reversal with GH, but not IGF-I, therapy. 1999

K A Robinson, and S M Willi, and S Bingel, and M G Buse
Division of Endocrinology, Diabetes, and Medical Genetics, Department of Medicine, Medical University of South Carolina, Charleston, South Carolina 29425-2222, USA.

Enhanced glucose flux via the hexosamine biosynthesis pathway (HNSP) has been implicated in insulin resistance. We measured L-glutamine:D-fructose-6-phosphate amidotransferase activity (GFAT, a rate-limiting enzyme) and concentrations of UDP-N-acetyl hexosamines (UDP-HexNAc, major products of HNSP) in muscle and liver of growth hormone (GH)-deficient male dwarf (dw) rats. All parameters measured, except body weight, were similar in 5-wk-old control and dw rats. Muscle GFAT activity declined progressively with age in controls and dw rats but was consistently 30-60% lower in 8- to 14-wk-old dw rats vs. age-matched controls; UDP-HexNAc concentrations in muscle were concomitantly 30% lower in dw rats vs. controls (P < 0.01). Concentrations of UDP-hexoses, GDP-mannose, and UDP in muscle were similar in control and dw rats. Muscle HNSP activity was similarly diminished in fed and fasted dw rats. In liver, only a small difference in GFAT activity was evident between controls and dw rats, and no differences in UDP-HexNAc concentrations were observed. Treatment with recombinant human GH (rhGH) for 5 days restored UDP-HexNAc to control levels in dw muscles (P < 0.01) and partially restored GFAT activity. Insulin-like growth factor I treatment was ineffective. We conclude that GH participates in HNSP regulation in muscle.

UI MeSH Term Description Entries
D007334 Insulin-Like Growth Factor I A well-characterized basic peptide believed to be secreted by the liver and to circulate in the blood. It has growth-regulating, insulin-like, and mitogenic activities. This growth factor has a major, but not absolute, dependence on GROWTH HORMONE. It is believed to be mainly active in adults in contrast to INSULIN-LIKE GROWTH FACTOR II, which is a major fetal growth factor. IGF-I,Somatomedin C,IGF-1,IGF-I-SmC,Insulin Like Growth Factor I,Insulin-Like Somatomedin Peptide I,Insulin Like Somatomedin Peptide I
D008099 Liver A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances. Livers
D008297 Male Males
D011917 Rats, Inbred Lew An inbred strain of rat that is used in BIOMEDICAL RESEARCH. Rats, Inbred Lewis,Rats, Lew,Inbred Lew Rat,Inbred Lew Rats,Inbred Lewis Rats,Lew Rat,Lew Rat, Inbred,Lew Rats,Lew Rats, Inbred,Lewis Rats, Inbred,Rat, Inbred Lew,Rat, Lew
D011994 Recombinant Proteins Proteins prepared by recombinant DNA technology. Biosynthetic Protein,Biosynthetic Proteins,DNA Recombinant Proteins,Recombinant Protein,Proteins, Biosynthetic,Proteins, Recombinant DNA,DNA Proteins, Recombinant,Protein, Biosynthetic,Protein, Recombinant,Proteins, DNA Recombinant,Proteins, Recombinant,Recombinant DNA Proteins,Recombinant Proteins, DNA
D004392 Dwarfism A genetic or pathological condition that is characterized by short stature and undersize. Abnormal skeletal growth usually results in an adult who is significantly below the average height. Nanism
D004435 Eating The consumption of edible substances. Dietary Intake,Feed Intake,Food Intake,Macronutrient Intake,Micronutrient Intake,Nutrient Intake,Nutritional Intake,Ingestion,Dietary Intakes,Feed Intakes,Intake, Dietary,Intake, Feed,Intake, Food,Intake, Macronutrient,Intake, Micronutrient,Intake, Nutrient,Intake, Nutritional,Macronutrient Intakes,Micronutrient Intakes,Nutrient Intakes,Nutritional Intakes
D005215 Fasting Abstaining from FOOD. Hunger Strike,Hunger Strikes,Strike, Hunger,Strikes, Hunger
D005945 Glutamine-Fructose-6-Phosphate Transaminase (Isomerizing) An enzyme that catalyzes the synthesis of fructose-6-phosphate plus GLUTAMINE from GLUTAMATE plus glucosamine-6-phosphate. Glucosamine Synthetase,Glucosaminephosphate Isomerase (Glutamine-Forming),Hexosephosphate Aminotransferase,2-Amino-2-Deoxy-D-Glucose-6-Phosphate Ketol-Isomerase,Glucosamine 6-Phosphate Synthetase,Glucosamine-6-Phosphate Synthase,Glucosaminephosphate Isomerase (Glutamine Forming),Glutamine-Fructose-6-P Aminotransferase,Glutamine-Fructose-6-Phosphate Aminotransferase,Glutamine:Fructose-6-Phosphate-Amidotransferase,2 Amino 2 Deoxy D Glucose 6 Phosphate Ketol Isomerase,6-Phosphate Synthetase, Glucosamine,Aminotransferase, Glutamine-Fructose-6-P,Aminotransferase, Glutamine-Fructose-6-Phosphate,Aminotransferase, Hexosephosphate,Glucosamine 6 Phosphate Synthase,Glucosamine 6 Phosphate Synthetase,Glutamine Fructose 6 P Aminotransferase,Glutamine Fructose 6 Phosphate Aminotransferase,Glutamine:Fructose 6 Phosphate Amidotransferase,Ketol-Isomerase, 2-Amino-2-Deoxy-D-Glucose-6-Phosphate
D006595 Hexosamines AMINO SUGARS created by adding an amine group to a hexose sugar. Hexosamine

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