Loss of the Par-1b/MARK2 polarity kinase leads to increased metabolic rate, decreased adiposity, and insulin hypersensitivity in vivo Academic Article uri icon

Overview

MeSH Major

  • Adipose Tissue
  • Adiposity
  • Cell Cycle Proteins
  • Gene Expression Regulation
  • Insulin
  • Insulin Resistance
  • Obesity
  • Protein-Serine-Threonine Kinases

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.

publication date

  • March 27, 2007

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC1838456

Digital Object Identifier (DOI)

  • 10.1073/pnas.0701179104

PubMed ID

  • 17372192

Additional Document Info

start page

  • 5680

end page

  • 5

volume

  • 104

number

  • 13