title: Loss of the Par-1b/MARK2 polarity kinase leads to increased metabolic rate, decreased adiposity, and insulin hypersensitivity in vivo.
abstract: Obesity is a major factor central to the development of insulin resistance and type 2 diabetes. The identification and characterization of genes involved in regulation of adiposity, insulin sensitivity, and glucose uptake are key to the design and development of new drug therapies for this disease. In this study, we show that the polarity kinase Par-1b/MARK2 is required for regulating glucose metabolism in vivo. Mice null for Par-1b were lean, insulin hypersensitive, resistant to high-fat diet-induced weight gain, and hypermetabolic. (18)F-FDG microPET and hyperinsulinemic-euglycemic clamp analyses demonstrated increased glucose uptake into white and brown adipose tissue, but not into skeletal muscle of Par-1b null mice relative to wild-type controls. Taken together, these data indicate that Par-1b is a regulator of glucose metabolism and adiposity in the whole animal and may be a valuable drug target for the treatment of both type 2 diabetes and obesity.
authors: Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, MO 63110-1093, USA.
authors: Jonathan B
authors: JB
authors: Hurov
authors: Mei
authors: M
authors: Huang
authors: Lynn S
authors: LS
authors: White
authors: Jochen
authors: J
authors: Lennerz
authors: Cheol Soo
authors: CS
authors: Choi
authors: You-Ree
authors: YR
authors: Cho
authors: Hyo-Jeong
authors: HJ
authors: Kim
authors: Julie L
authors: JL
authors: Prior
authors: David
authors: D
authors: Piwnica-Worms
authors: Lewis C
authors: LC
authors: Cantley
authors: Jason K
authors: JK
authors: Kim
authors: Gerald I
authors: GI
authors: Shulman
authors: Helen
authors: H
authors: Piwnica-Worms
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism*; D050154:Adiposity / Q000235:genetics*; D000818:Animals; D018797:Cell Cycle Proteins / Q000502:physiology*; D005260:Female; D005786:Gene Expression Regulation; D005947:Glucose / Q000378:metabolism; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance / Q000235:genetics*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009765:Obesity / Q000235:genetics*; D017346:Protein Serine-Threonine Kinases / Q000502:physiology*; D013997:Time Factors
chemical_list: D018797:Cell Cycle Proteins; D007328:Insulin; C122043:Mark2 protein, mouse; D017346:Protein Serine-Threonine Kinases; D005947:Glucose