Resistance to Exercise-Induced Increase in Glucose Uptake During Hyperinsulinemia in Insulin-Resistant Skeletal Muscle of Patients With Type 1 Diabetes

• Published in: Diabetes (New York, N.Y.) Vol. 50; no. 6; pp. 1371 - 1377
• Main Authors: Peltoniemi, Pauliina, Yki-Järvinen, Hannele, Oikonen, Vesa, Oksanen, Airi, Takala, Teemu O., Rönnemaa, Tapani, Erkinjuntti, Matti, Knuuti, M. Juhani, Nuutila, Pirjo
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Diabetes Association 01.06.2001
• Subjects: Adult; Biological and medical sciences; Blood Glucose - metabolism; Defects; Dextrose; Diabetes; Diabetes Mellitus, Type 1 - physiopathology; Diabetes. Impaired glucose tolerance; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Exercise - physiology; Glucose; Glucose - metabolism; Humans; Hyperinsulinism - metabolism; Insulin; Insulin Resistance; Isometric exercise; Kinases; Legs; Male; Medical sciences; Metabolism; Metabolites; Muscle, Skeletal - blood supply; Muscle, Skeletal - diagnostic imaging; Muscle, Skeletal - metabolism; Musculoskeletal system; Oxygen Consumption; Phosphorylation; Physiological aspects; Regional Blood Flow; Striated muscle; Thigh; Tomography, Emission-Computed; Type 1 diabetes; Finland; Endocrinopathy; Physical exercise; Human; Immunopathology; Hyperinsulinemia; Pancreatic hormone; Autoimmune disease; Glucose; Striated muscle; Insulin; Uptake; Target tissue resistance; Experimental disease; Insulin dependent diabetes
• ISSN: 0012-1797; 1939-327X
• DOI: 10.2337/diabetes.50.6.1371

Resistance to Exercise-Induced Increase in Glucose Uptake During Hyperinsulinemia in Insulin-Resistant Skeletal Muscle of Patients With Type 1 Diabetes Pauliina Peltoniemi 1 , Hannele Yki-Järvinen 2 , Vesa Oikonen 1 , Airi Oksanen 3 , Teemu O. Takala 1 , Tapani Rönnemaa 4 , Matti Erkinjuntti 5 , M. Juhani Knuuti 1 and Pirjo Nuutila 1 4 1 Turku PET Centre, University of Turku, Turku, Finland 2 Department of Medicine, University of Helsinki, Helsinki, Finland; and the Departments of 3 Rehabilitation and Physical Medicine 4 Medicine, and 5 Clinical Neurophysiology, University of Turku, Turku, Finland Abstract Insulin and exercise have been shown to activate glucose transport at least in part via different signaling pathways. However, it is unknown whether insulin resistance is associated with a defect in the ability of an acute bout of exercise to enhance muscle glucose uptake in vivo. We compared the abilities of insulin and isometric exercise to stimulate muscle blood flow and glucose uptake in 12 men with type 1 diabetes (age 24 ± 1 years, BMI 23.0 ± 0.4 kg/m 2 ) and in 11 age- and weight-matched nondiabetic men (age 25 ± 1 years, BMI 22.3 ± 0.6 kg/m 2 ) during euglycemic hyperinsulinemia (1 mU · kg −1 · min −1 insulin infusion for 150 min). One-legged exercise was performed at an intensity of 10% of maximal isometric force for 105 min (range 45–150). Rates of muscle blood flow, oxygen consumption, and glucose uptake were quantitated simultaneously in both legs using [ 15 O]water, [ 15 O]oxygen, [ 18 F]-2-fluoro-2-deoxy- d -glucose, and positron emission tomography. Resting rates of oxygen consumption were similar during hyperinsulinemia between the groups (2.4 ± 0.3 vs. 2.0 ± 0.5 ml · kg −1 muscle · min −1 ; normal subjects versus patients with type 1 diabetes, NS), and exercise increased oxygen consumption similarly in both groups (25.3 ± 4.3 vs. 20.1 ± 3.0 ml · kg −1 muscle · min −1 , respectively, NS). Rates of insulin-stimulated muscle blood flow and the increments in muscle blood flow induced by exercise were also similar in normal subjects (129 ± 14 ml · kg −1 · min −1 ) and in patients with type 1 diabetes (115 ± 12 ml · kg −1 · min −1 ). The patients with type 1 diabetes exhibited resistance to both insulin stimulation of glucose uptake (34 ± 6 vs. 76 ± 9 μmol · kg −1 muscle · min −1 , P < 0.001) and also to the exercise-induced increment in glucose uptake (82 ± 15 vs. 162 ± 29 μmol · kg −1 muscle · min −1 , P < 0.05). We conclude that the ability of exercise to increase insulin-stimulated glucose uptake in vivo is blunted in patients with insulin-resistant type 1 diabetes compared with normal subjects. This could be caused by either separate or common defects in exercise- and insulin-stimulated pathways. Footnotes Address correspondence and reprint requests to Dr. Pauliina Peltoniemi, Turku PET Centre, University of Turku, P.O. Box 52, FIN-20520 Turku, Finland. E-mail: papelto{at}utu.fi . Received for publication 16 June 2000 and accepted in revised form 21 February 2001. AMPK, AMP-activated protein kinase; FDG, 2-fluoro-2-deoxy- d -glucose; FFA, free fatty acid; IRS-1, insulin receptor substrate-1; MIRKO, muscle-specific insulin-receptor knockout; PET, positron emission tomography; PI, phosphatidylinositol; rGU, rate of glucose uptake.