Insulin conserves glucose while insulin resistance reduces the body?s conservation of glucose. Insulin resistance is associated with many health complications. Many people with insulin resistance develop diabetes. For unknown reasons, insulin resistance also promotes heart disease and breast cancer. Liver insulin resistance increases in the obese state partly because the expansion of fat tissue leads to low levels of circulating adiponectin. We are investigating the adiponectin pathway that increases insulin sensitivity in the liver. Our specific goals are to determine the role of (1) mTOR, a potential target of adiponectin and inhibitor of glucose production, (2) AMPK, a target of adiponectin that inhibits glucose production, (3) lysosome activity, a cellular process of protein degradation that provides amino acids for glucose production. The insight we gain could lead to a better understanding of adiponectin action in the liver and more effective interventions for the treatment of insulin resistance.? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Scientist Development Award - Research & Training (K01)
Project #
5K01DK075573-02
Application #
7261226
Study Section
Diabetes, Endocrinology and Metabolic Diseases B Subcommittee (DDK)
Program Officer
Hyde, James F
Project Start
2006-08-01
Project End
2009-07-31
Budget Start
2007-08-01
Budget End
2008-07-31
Support Year
2
Fiscal Year
2007
Total Cost
$114,233
Indirect Cost
Name
University of North Carolina Chapel Hill
Department
Nutrition
Type
Schools of Public Health
DUNS #
608195277
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599
Combs, Terry P; Snell-Bergeon, Janet K; Maahs, David M et al. (2015) Adiponectin-SOGA Dissociation in Type 1 Diabetes. J Clin Endocrinol Metab 100:E1065-73
Combs, Terry P; Marliss, Errol B (2014) Adiponectin signaling in the liver. Rev Endocr Metab Disord 15:137-47
Croteau-Chonka, Damien C; Wu, Ying; Li, Yun et al. (2012) Population-specific coding variant underlies genome-wide association with adiponectin level. Hum Mol Genet 21:463-71
Cowherd, Rachael B; Cowerd, Rachael B; Asmar, Melissa M et al. (2010) Adiponectin lowers glucose production by increasing SOGA. Am J Pathol 177:1936-45
Alderman, J McKee; Flurkey, Kevin; Brooks, Natasha L et al. (2009) Neuroendocrine inhibition of glucose production and resistance to cancer in dwarf mice. Exp Gerontol 44:26-33
Raetzsch, Carl F; Brooks, Natasha L; Alderman, J McKee et al. (2009) Lipopolysaccharide inhibition of glucose production through the Toll-like receptor-4, myeloid differentiation factor 88, and nuclear factor kappa b pathway. Hepatology 50:592-600
Lewin, Tal M; de Jong, Hendrik; Schwerbrock, Nicole J M et al. (2008) Mice deficient in mitochondrial glycerol-3-phosphate acyltransferase-1 have diminished myocardial triacylglycerol accumulation during lipogenic diet and altered phospholipid fatty acid composition. Biochim Biophys Acta 1781:352-8
Brooks, Natasha L; Trent, Chad M; Raetzsch, Carl F et al. (2007) Low utilization of circulating glucose after food withdrawal in Snell dwarf mice. J Biol Chem 282:35069-77