Pascale Perret1,2, Lotfi Slimani3,4, Arnaud Briat3,4, Danièle Villemain3,4, Serge Halimi5, Jacques Demongeot4,6, Daniel Fagret3,4, Catherine Ghezzi3,4. 1. INSERM, E340, 38000 Grenoble,, France. pascale.perret@ujf-grenoble.fr. 2. Univ Grenoble, 38000 Grenoble,, France. pascale.perret@ujf-grenoble.fr. 3. INSERM, E340, 38000 Grenoble,, France. 4. Univ Grenoble, 38000 Grenoble,, France. 5. CHRU Grenoble, Hôpital Michallon, Service de Diabétologie, , 38000 Grenoble,, France. 6. CNRS, UMR 5525, 38000 Grenoble, , France.
Abstract
PURPOSE: Insulin resistance, characterised by an insulin-stimulated glucose transport defect, is an important feature of the pre-diabetic state that has been observed in numerous pathological disorders. The purpose of this study was to assess variations in glucose transport in rats using (125)I-6-deoxy-6-iodo-D-glucose (6DIG), a new tracer of glucose transport proposed as an imaging tool to assess insulin resistance in vivo. METHODS: Two protocols were performed, a hyperinsulinaemic-euglycaemic clamp and a normoinsulinaemic-normoglycaemic protocol, in awake control and insulin-resistant fructose-fed rats. The tracer was injected at steady state, and activity in 11 tissues and the blood was assessed ex vivo at several time points. A multicompartmental mathematical model was developed to obtain fractional transfer coefficients of 6DIG from the blood to the organs. RESULTS: Insulin sensitivity of fructose-fed rats, estimated by the glucose infusion rate, was reduced by 40% compared with control rats. At steady state, 6DIG uptake was significantly stimulated by insulin in insulin-sensitive tissues of control rats (basal versus insulin: diaphragm, p < 0.01; muscle, p<0.05; heart, p<0.001), whereas insulin did not stimulate 6DIG uptake in insulin-resistant fructose-fed rats. Moreover, in these tissues, the fractional transfer coefficients of entrance were significantly increased with insulin in control rats (basal vs insulin: diaphragm, p<0.001; muscle, p<0.001; heart, p<0.01) whereas no significant changes were observed in fructose-fed rats. CONCLUSION: This study sets the stage for the future use of 6DIG as a non-invasive means for the evaluation of insulin resistance by nuclear imaging.
PURPOSE: Insulin resistance, characterised by an insulin-stimulated glucose transport defect, is an important feature of the pre-diabetic state that has been observed in numerous pathological disorders. The purpose of this study was to assess variations in glucose transport in rats using (125)I-6-deoxy-6-iodo-D-glucose (6DIG), a new tracer of glucose transport proposed as an imaging tool to assess insulin resistance in vivo. METHODS: Two protocols were performed, a hyperinsulinaemic-euglycaemic clamp and a normoinsulinaemic-normoglycaemic protocol, in awake control and insulin-resistant fructose-fed rats. The tracer was injected at steady state, and activity in 11 tissues and the blood was assessed ex vivo at several time points. A multicompartmental mathematical model was developed to obtain fractional transfer coefficients of 6DIG from the blood to the organs. RESULTS: Insulin sensitivity of fructose-fed rats, estimated by the glucose infusion rate, was reduced by 40% compared with control rats. At steady state, 6DIG uptake was significantly stimulated by insulin in insulin-sensitive tissues of control rats (basal versus insulin: diaphragm, p < 0.01; muscle, p<0.05; heart, p<0.001), whereas insulin did not stimulate 6DIG uptake in insulin-resistant fructose-fed rats. Moreover, in these tissues, the fractional transfer coefficients of entrance were significantly increased with insulin in control rats (basal vs insulin: diaphragm, p<0.001; muscle, p<0.001; heart, p<0.01) whereas no significant changes were observed in fructose-fed rats. CONCLUSION: This study sets the stage for the future use of 6DIG as a non-invasive means for the evaluation of insulin resistance by nuclear imaging.
Authors: Kirsi A Virtanen; Peter Lönnroth; Riitta Parkkola; Pauliina Peltoniemi; Markku Asola; Tapio Viljanen; Tuula Tolvanen; Juhani Knuuti; Tapani Rönnemaa; Risto Huupponen; Pirjo Nuutila Journal: J Clin Endocrinol Metab Date: 2002-08 Impact factor: 5.958
Authors: J Eriksson; A Franssila-Kallunki; A Ekstrand; C Saloranta; E Widén; C Schalin; L Groop Journal: N Engl J Med Date: 1989-08-10 Impact factor: 91.245