title: Insulin-mimicking bioactivities of acylated inositol glycans in several mouse models of diabetes with or without obesity.
abstract: Insulin-mimetic species of low molecular weight are speculated to mediate some intracellular insulin actions. These inositol glycans, which are generated upon insulin stimulation from glycosylphosphatidylinositols, might control the activity of a multitude of insulin effector enzymes. Acylated inositol glycans (AIGs) are generated by cleavage of protein-free GPI precursors through the action of GPI-specific phospholipase C (GPI-PLC) and D (GPI-PLD). We synthesized AIGs (IG-1, IG-2, IG-13, IG-14, and IG-15) and then evaluated their insulin-mimicking bioactivities. IG-1 significantly stimulated glycogen synthesis and lipogenesis in 3T3-L1 adipocytes and rat isolated adipocytes dose-dependently. IG-2 significantly stimulated lipogenesis in rat isolated adipocytes dose-dependently. IG-15 also enhanced glycogen synthesis and lipogenesis in 3T3-L1 adipocytes. The administration of IG-1 decreased plasma glucose, increased glycogen content in liver and skeletal muscles and improved glucose tolerance in C57B6N mice with normal diets. The administration of IG-1 decreased plasma glucose in STZ-diabetic C57B6N mice. The treatment of IG-1 decreased plasma glucose, increased glycogen content in liver and skeletal muscles and improved glucose tolerance in C57B6N mice with high fat-diets and db/db mice. The long-term treatment of IG-1 decreased plasma glucose and reduced food intake and body weight in C57B6N mice with high fat-diets and ob/ob mice. Thus, IG-1 has insulin-mimicking bioactivities and improves glucose tolerance in mice models of diabetes with or without obesity.
authors: Department of Diabetes and Metabolism, Tohoku University Hospital, Sendai, Japan; Diabetes Center, Ohta Nishinouchi Hospital, Koriyama, Japan.
authors: Susumu
authors: S
authors: Suzuki
authors: Department of Diabetes and Metabolism, Tohoku University Hospital, Sendai, Japan.
authors: Chitose
authors: C
authors: Suzuki
authors: Department of Diabetes and Metabolism, Tohoku University Hospital, Sendai, Japan.
authors: Yoshinori
authors: Y
authors: Hinokio
authors: Department of Diabetes and Metabolism, Tohoku University Hospital, Sendai, Japan.
authors: Yasushi
authors: Y
authors: Ishigaki
authors: Department of Diabetes and Metabolism, Tohoku University Hospital, Sendai, Japan.
authors: Hideki
authors: H
authors: Katagiri
authors: Graduate School of Biomedical Engineering, Tohoku University, Sendai, Japan.
authors: Makoto
authors: M
authors: Kanzaki
authors: Department of Chemistry, Tufts University, Medford, Massachusetts, United States of America.
authors: Viatcheslav N
authors: VN
authors: Azev
authors: Department of Chemistry, Tufts University, Medford, Massachusetts, United States of America.
authors: Nilanjana
authors: N
authors: Chakraborty
authors: Department of Chemistry, Tufts University, Medford, Massachusetts, United States of America; Department of Chemistry, San Jose State University, San Jose, California, United States of America.
authors: Marc
authors: M
authors: d'Alarcao
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism; D000821:Animal Feed; D000818:Animals; D001786:Blood Glucose; D003921:Diabetes Mellitus, Experimental / Q000150:complications* / Q000188:drug therapy / Q000378:metabolism*; D004195:Disease Models, Animal; D006003:Glycogen / Q000096:biosynthesis; D007294:Inositol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D007328:Insulin / Q000008:administration & dosage / Q000494:pharmacology*; D050155:Lipogenesis / Q000187:drug effects; D051379:Mice; D018716:Molecular Mimicry; D009765:Obesity / Q000150:complications*; D011134:Polysaccharides / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D013997:Time Factors
chemical_list: D001786:Blood Glucose; D007328:Insulin; D011134:Polysaccharides; C068698:inositol-glycan; D007294:Inositol; D006003:Glycogen