INTRODUCTION: Glucose intolerance or overt diabetes occurs in 80% of patients with pancreatic cancer (PC). This associated metabolic disorder includes peripheral insulin resistance, which may be caused by factors produced by the PC. The mechanism underlying PC-associated insulin resistance has not been clearly defined. AIM: To characterize basal and insulin-stimulated glucose transport, phosphatidylinositol (PI) 3-kinase activity, and glucose transporter 4 (GLUT4) in skeletal muscles of PC patients. METHODOLOGY: Skeletal muscle samples were obtained from the abdominal wall of 17 PC patients during surgery. Control muscles were sampled in the same way from 11 donors undergoing abdominal surgery for benign diseases. PI 3-kinase activity, glucose transport, and GLUT4 were assessed in vitro in these muscles. RESULTS: In the presence of physiologic concentrations of insulin, glucose transport and PI 3-kinase activity were significantly decreased in the PC group compared with controls. At supraphysiologic insulin concentrations, glucose transport was significantly decreased but PI 3-kinase activity was normalized. In the absence of insulin, these parameters were not significantly different between PC and control groups. Muscle GLUT4 contents were similar between PC and control groups. CONCLUSION: Defects in insulin-mediated PI 3-kinase activity and glucose transport contribute to the insulin resistance in patients with PC.
INTRODUCTION:Glucose intolerance or overt diabetes occurs in 80% of patients with pancreatic cancer (PC). This associated metabolic disorder includes peripheral insulin resistance, which may be caused by factors produced by the PC. The mechanism underlying PC-associated insulin resistance has not been clearly defined. AIM: To characterize basal and insulin-stimulated glucose transport, phosphatidylinositol (PI) 3-kinase activity, and glucose transporter 4 (GLUT4) in skeletal muscles of PC patients. METHODOLOGY: Skeletal muscle samples were obtained from the abdominal wall of 17 PC patients during surgery. Control muscles were sampled in the same way from 11 donors undergoing abdominal surgery for benign diseases. PI 3-kinase activity, glucose transport, and GLUT4 were assessed in vitro in these muscles. RESULTS: In the presence of physiologic concentrations of insulin, glucose transport and PI 3-kinase activity were significantly decreased in the PC group compared with controls. At supraphysiologic insulin concentrations, glucose transport was significantly decreased but PI 3-kinase activity was normalized. In the absence of insulin, these parameters were not significantly different between PC and control groups. Muscle GLUT4 contents were similar between PC and control groups. CONCLUSION: Defects in insulin-mediated PI 3-kinase activity and glucose transport contribute to the insulin resistance in patients with PC.
Authors: Gaurav Aggarwal; Vijaya Ramachandran; Naureen Javeed; Thiruvengadam Arumugam; Shamit Dutta; George G Klee; Eric W Klee; Thomas C Smyrk; William Bamlet; Jing Jing Han; Natalia B Rumie Vittar; Mariza de Andrade; Debabrata Mukhopadhyay; Gloria M Petersen; Martin E Fernandez-Zapico; Craig D Logsdon; Suresh T Chari Journal: Gastroenterology Date: 2012-09-06 Impact factor: 22.682
Authors: Jukka Kemppainen; Hiroki Tsuchida; Kira Stolen; Håkan Karlsson; Marie Björnholm; Olli J Heinonen; Pirjo Nuutila; Anna Krook; Juhani Knuuti; Juleen R Zierath Journal: J Physiol Date: 2003-05-09 Impact factor: 5.182
Authors: Thomas L Schmitt; Marcus E Martignoni; Jeannine Bachmann; Kerstin Fechtner; Helmut Friess; Ralf Kinscherf; Wulf Hildebrandt Journal: J Mol Med (Berl) Date: 2007-03-02 Impact factor: 5.606