Abstract

This project will test the following specific aims: 1) the effects of high-fat (HF) and high-sucrose (HS) diets on glucose uptake, hepatic glucose cycling and hepatic glycogen synthesis using new methods. 2) Effects of these diets on hepatic fatty acid uptake, oxidation and gluconeogenesis, and the regulatory steps involved. 3) The role of increased Na K ATPase activity on the metabolism of fat and glucose. 4) Contribution of microsomal glucose-6 phosphatase to hepatic insulin resistance. Hepatic glucose uptake will be measured by euglycemic hyperinsulinemic clamp, accompanied by mesenteric glucose infusion. Glucose cycling will be measured using 6-3H glucose and 2-3H-glucose. Fatty acid oxidation will be measured as C02 production from dehydroxyacetone (DHA) will also be measured both in the presence and absence of ouabain. To test whether the increased N K ATPase activity is due to increased synthesis of diacylglycerol and consequently activation of protein kinase C, synthesis of neutral and phospholipids from U-14C-glucose and membrane bound PKC activity will be measured. Finally, to explain the decreased Km of G-6Pase for G6P during HS diet, and increased Vmax during HF diet, kinetics of this enzyme will be measured in the intact and disrupted microsomes.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK055386-05
Application #
6381481
Study Section
Nutrition Study Section (NTN)
Program Officer
Laughlin, Maren R
Project Start
1998-06-01
Project End
2003-05-31
Budget Start
2001-06-01
Budget End
2003-05-31
Support Year
5
Fiscal Year
2001
Total Cost
$148,988
Indirect Cost

  Institution

Name
University of Colorado Denver
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
065391526
City
Aurora
State
CO
Country
United States
Zip Code
80045

  Publications

Puljak, Livia; Pagliassotti, Michael J; Wei, Yuren et al. (2005) Inhibition of cellular responses to insulin in a rat liver cell line. A role for PKC in insulin resistance. J Physiol 563:471-82
Wei, Yuren; Bizeau, Michael E; Pagliassotti, Michael J (2004) An acute increase in fructose concentration increases hepatic glucose-6-phosphatase mRNA via mechanisms that are independent of glycogen synthase kinase-3 in rats. J Nutr 134:545-51
Pagliassotti, Michael J; Wei, Yuren; Bizeau, Michael E (2003) Glucose-6-phosphatase activity is not suppressed but the mRNA level is increased by a sucrose-enriched meal in rats. J Nutr 133:32-7
Yamashita, Hiroshi; Shao, Jianhua; Qiao, Liping et al. (2003) Effect of spontaneous gestational diabetes on fetal and postnatal hepatic insulin resistance in Lepr(db/+) mice. Pediatr Res 53:411-8
Bizeau, Michael E; MacLean, Paul S; Johnson, Ginger C et al. (2003) Skeletal muscle sterol regulatory element binding protein-1c decreases with food deprivation and increases with feeding in rats. J Nutr 133:1787-92
Commerford, S Renee; Ferniza, Jennifer B; Bizeau, Michael E et al. (2002) Diets enriched in sucrose or fat increase gluconeogenesis and G-6-Pase but not basal glucose production in rats. Am J Physiol Endocrinol Metab 283:E545-55
Bizeau, M E; Thresher, J S; Pagliassotti, M J (2001) A high-sucrose diet increases gluconeogenic capacity in isolated periportal and perivenous rat hepatocytes. Am J Physiol Endocrinol Metab 280:E695-702
Bizeau, M E; Thresher, J S; Pagliassotti, M J (2001) Sucrose diets increase glucose-6-phosphatase and glucose release and decrease glucokinase in hepatocytes. J Appl Physiol 91:2041-6
Commerford, S R; Bizeau, M E; McRae, H et al. (2001) Hyperglycemia compensates for diet-induced insulin resistance in liver and skeletal muscle of rats. Am J Physiol Regul Integr Comp Physiol 281:R1380-9
Bizeau, M E; Short, C; Thresher, J S et al. (2001) Increased pyruvate flux capacities account for diet-induced increases in gluconeogenesis in vitro. Am J Physiol Regul Integr Comp Physiol 281:R427-33

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