Loss of the Par-1b/MARK2 polarity kinase leads to increased metabolic rate, decreased adiposity, and insulin hypersensitivity in vivo.
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.
Hurov
Jonathan B
JB
Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, MO 63110-1093, USA.
Huang
Mei
M
White
Lynn S
LS
Lennerz
Jochen
J
Choi
Cheol Soo
CS
Cho
You-Ree
YR
Kim
Hyo-Jeong
HJ
Prior
Julie L
JL
Piwnica-Worms
David
D
Cantley
Lewis C
LC
Kim
Jason K
JK
Shulman
Gerald I
GI
Piwnica-Worms
Helen
H
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
D018797:Cell Cycle Proteins; D007328:Insulin; C122043:Mark2 protein, mouse; D017346:Protein Serine-Threonine Kinases; D005947:Glucose