Introduction 1 3 3 3 2 3 PTEN 4 6 PTEN 4 8 3 Pten 9 11 Pten Pten −/− 6 12 Pten Pten +/− Pten 6 12 14 Pten +/− 12 14 Pten Materials and methods Experimental animals Pten +/− 12 12 Blood glucose determination Determination of insulin in plasma g Isolation of pancreatic islets and glucose-stimulated insulin release 15 Fluorescent immunohistochemistry of pancreatic islets 16 Pten +/− Beta cell mass calculation 18 18 18 18 68 Pten +/− 18 18 18 18 Primary myocyte culture Pten +/− 17 g 18 3 Pten +/− 4 2 3 3 3 19 Determination of cell-surface GLUT1 and GLUT4 levels Western immunoblotting for PKB, phospho-PKB and phospho-glycogen synthase kinase 3 (GSK3)-α/β Statistical analysis t Results Pten +/− Pten +/− Pten +/− Pten +/− 1 Pten +/− Pten +/− 1 Pten +/− Pten +/− 1 Pten +/− Table 1 Pten +/−   Mean blood glucose±SD (mmol/l) p t Wild-type +/− Ad libitum feeding n n 0.006 Fasting n n 0.008 Fig. 1 Pten +/− a white circles Pten +/− black circles b white circles Pten +/− black circles  Pten +/− 2 2 Pten +/− Pten +/+ Pten +/− Materials and methods Pten +/+ Pten +/− p n Pten +/+ Pten +/− p n Table 2 Pten +/−   Mean plasma insulin±SD (ng/ml) p t n +/− n Fasting 0.50 ± 0.04 0.36 ± 0.10 0.05 Post-glucose challenge 1.8 ± 0.5 2.4 ± 0.4 >0.05 (not significant) Pten +/− 2 Pten Pten +/− 3 Fig. 2 green red a Pten +/− b Materials and methods  Table 3 Pten +/+ Pten +/−   Mean beta cell mass±SE (mg) Pten +/+ n Pten +/− n 10 20 18 18 21 Pten +/− 18 18 3 18 Pten +/− 3 Fig. 3 18 Pten +/− 18 18 a–f 18 Pten +/− a b c d e f 18 Materials and methods g 18 18 circles Pten +/− triangles n  Pten +/− 14 22 24 Pten +/− Pten +/− 3 4 Pten +/− Pten +/− Pten +/− 18 Pten Fig. 4 a 3 Pten +/− 3 White circles black circles white triangles Pten +/− black triangles Pten +/− b WT Pten +/− Materials and methods  25 3 Pten +/− 4 4 Pten +/− 26 27 Pten +/− 5 Pten +/− Pten +/− Pten +/+ 5 Pten +/− Pten +/+ 5 Fig. 5 WT  Discussion Pten 9 11 28 29 Pten 14 22 24 30 Pten 1 3 31 32 9 11 28 Pten +/− 3 +/− Pten 25 33 36 Pten +/− Pten +/− 37 3 3 38 40 38 41 43 3 44 Ship2 45 Phox2a Nature 46 46 47 Pten 48 49 Pten +/− Pten 9 44 44 12 14 23 Pten