Germline manipulation of glucose homeostasis via alteration of glucose transporter levels in skeletal muscle

• Published in: The Journal of biological chemistry Vol. 268; no. 25; pp. 18442 - 18445
• Main Authors: Marshall, B.A., Ren, J.M., Johnson, D.W., Gibbs, E.M., Lillquist, J.S., Soeller, W.C., Holloszy, J.O., Mueckler, M.
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Elsevier Inc 05.09.1993; American Society for Biochemistry and Molecular Biology
• Subjects: 3-Hydroxybutyric Acid; Animals; azucar en sangre; Base Sequence; Biological and medical sciences; Biological Transport; Blood Glucose - metabolism; blood sugar; Blotting, Southern; carbohydrate metabolism; Carbohydrates; chemoreceptors; chimiorecepteur; expresion genica; expression des genes; Fundamental and applied biological sciences. Psychology; Gene Expression; gene transfer; genero humano; genetic transformation; genre humain; glucosa; glucose; Glucose Transporter Type 1; homeostasie; Homeostasis; hormonas; hormone; hormones; Humans; Hydroxybutyrates - blood; insulin; insulina; insuline; Lactates - blood; Lactic Acid; Mammalia; mankind; metabolisme des glucides; metabolismo de carbohidratos; Metabolisms and neurohumoral controls; Mice; Mice, Inbred C57BL; Mice, Transgenic; Molecular Sequence Data; Monosaccharide Transport Proteins - genetics; Monosaccharide Transport Proteins - metabolism; muscle; muscles; Muscles - metabolism; musculos; proteinas; proteine; proteins; quimioreceptors; raton; Rats; Sarcolemma - metabolism; souris; sucre du sang; transferencia de genes; transfert de gene; transformacion genetica; transformation genetique; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Vertebrata; Regulation(control); Mammalia; Mouse; Biological transport; Rodentia; Transgenic animal; Homeostasis; Glucose; Striated muscle; Carrier protein
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1016/S0021-9258(17)46645-2

Transgenic mice were constructed that overexpress the human Glut1 glucose transporter in skeletal muscle. Transcription of the human Glut1 cDNA was driven by the rat myosin light chain 2 promoter. Soleus and quadriceps muscles from transgenic mice expressed increased levels of Glut1 protein relative to muscles obtained from nontransgenic littermates, but there was no difference in the level of Glut4 protein between the two groups. Skeletal muscles isolated from the transgenic animals exhibited 3-4-fold increases in basal glucose uptake relative to muscles obtained from nontransgenic littermates. Muscles isolated from nontransgenic littermates exhibited 2-3-fold increases in glucose transport after incubation in the presence of insulin, but no insulin-stimulated increase in transport was observed in the muscles of transgenic mice. Plasma glucose levels were reduced by 18 and 30%, respectively, in fed and fasted transgenic mice relative to their nontransgenic siblings, but insulin and glucagon levels were not significantly different between the two groups. Glucose disposal following an oral glucose load was markedly enhanced in the transgenic animals, and plasma lactate and beta-OH-butyrate levels were elevated in both fed and fasted transgenic mice. These data strongly support the hypothesis that glucose transport plays a key role in whole body glucose homeostasis. They also demonstrate that the level of a glucose transporter in skeletal muscle can significantly influence the blood glucose set point and alter the levels of other fuel metabolites in the blood.