title: Targeted genetic inactivation of N-acetylglucosaminyltransferase-IVa impairs insulin secretion from pancreatic beta cells and evokes type 2 diabetes.
abstract: The biological significance of protein N-glycosylation has been elucidated using a mouse model bearing a genetic mutation of N-acetylglucosaminyltransferases (GnTs), which initiate the formation of specific branch structures on the mannose core of N-glycans. These glycosylation defects evoked a variety of abnormalities and disorders in specific cell types, tissues, and the whole body, reflecting functional requirements. N-Acetylglucosaminyltransferase-IVa (GnT-IVa) initiates the GlcNAcbeta1-4 branch synthesis on the Manalpha1-3 arm of the N-glycan core thereby increasing N-glycan branch complexity. To investigate the physiological function of GnT-IVa, we engineered and characterized GnT-IVa-deficient mice. GnT-IVa-deficient mice showed a metabolic disorder subsequently diagnosed as type 2 diabetes. In this chapter, methods for characterizing GnT-IVa-deficient mice by physiological analyses to detect metabolic alterations and biochemical analyses using primary isolated pancreatic beta cells are summarized and discussed.
authors.affiliation: Department of Disease Glycomics, The Institute of Scientific and Industrial Research, Osaka University, Ibaraki, Osaka, Japan.
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Ohtsubo
mesh_terms: D000818:Animals; D001483:Base Sequence; D002478:Cells, Cultured; D003924:Diabetes Mellitus, Type 2 / Q000209:etiology* / Q000503:physiopathology; D004789:Enzyme Activation / Q000235:genetics; D018390:Gene Targeting; D007150:Immunohistochemistry; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000201:enzymology*; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D017351:N-Acetylglucosaminyltransferases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
chemical_list: D007328:Insulin; D017351:N-Acetylglucosaminyltransferases; C038111:alpha-1,3-mannosylglycoprotein beta-1,4-N-acetylglucosaminyltransferase