Lipocalin-13 regulates glucose metabolism by both insulin-dependent and insulin-independent mechanisms.
Insulin sensitivity is impaired in obesity, and insulin resistance is the primary risk factor for type 2 diabetes. Here we show that lipocalin-13 (LCN13), a lipocalin superfamily member, is a novel insulin sensitizer. LCN13 was secreted by multiple cell types. Circulating LCN13 was markedly reduced in mice with obesity and type 2 diabetes. Three distinct approaches were used to increase LCN13 levels: LCN13 transgenic mice, LCN13 adenoviral infection, and recombinant LCN13 administration. Restoration of LCN13 significantly ameliorated hyperglycemia, insulin resistance, and glucose intolerance in mice with obesity. LCN13 enhanced insulin signaling not only in animals but also in cultured adipocytes. Recombinant LCN13 increased the ability of insulin to stimulate glucose uptake in adipocytes and to suppress hepatic glucose production (HGP) in primary hepatocyte cultures. Additionally, LCN13 alone was able to suppress HGP, whereas neutralization of LCN13 increased HGP in primary hepatocyte cultures. These data suggest that LCN13 regulates glucose metabolism by both insulin-dependent and insulin-independent mechanisms. LCN13 and LCN13-related molecules may be used to treat insulin resistance and type 2 diabetes.
Department of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, MI 48109-0622, USA.
Kae Won
KW
Cho
Yingjiang
Y
Zhou
Liang
L
Sheng
Liangyou
L
Rui
D041721:3T3-L1 Cells; D000256:Adenoviridae / Q000235:genetics; D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000378:metabolism; D004041:Dietary Fats; D005786:Gene Expression Regulation / Q000187:drug effects; D005947:Glucose / Q000378:metabolism*; D018149:Glucose Intolerance / Q000150:complications / Q000378:metabolism; D006943:Hyperglycemia / Q000150:complications / Q000378:metabolism; D007328:Insulin / Q000378:metabolism* / Q000494:pharmacology; D007333:Insulin Resistance; D054834:Lipocalins / Q000235:genetics / Q000378:metabolism*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009765:Obesity / Q000150:complications / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects
D004041:Dietary Fats; D007328:Insulin; D054834:Lipocalins; C556083:lipocalin-13 protein, mouse; D005947:Glucose