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Item Hepatic glucose uptake and disposition during short-term high-fat vs. high-fructose feeding(American Physiological Society (APS), 2014-07-15) Coate, Katie C.; Kraft, Guillaume; Moore, Mary Courtney; Smith, Marta S.; Ramnanan, Christopher; Irimia, Jose M.; Roach, Peter J.; Farmer, Ben; Neal, Doss W.; Williams, Phil; Cherrington, Alan D.; Department of Biochemistry & Molecular Biology, IU School of MedicineIn dogs consuming a high-fat and -fructose diet (52 and 17% of total energy, respectively) for 4 wk, hepatic glucose uptake (HGU) in response to hyperinsulinemia, hyperglycemia, and portal glucose delivery is markedly blunted with reduction in glucokinase (GK) protein and glycogen synthase (GS) activity. The present study compared the impact of selective increases in dietary fat and fructose on liver glucose metabolism. Dogs consumed weight-maintaining chow (CTR) or hypercaloric high-fat (HFA) or high-fructose (HFR) diets diet for 4 wk before undergoing clamp studies with infusion of somatostatin and intraportal insulin (3–4 times basal) and glucagon (basal). The hepatic glucose load (HGL) was doubled during the clamp using peripheral vein (Pe) glucose infusion in the first 90 min (P1) and portal vein (4 mg·kg−1·min−1) plus Pe glucose infusion during the final 90 min (P2). During P2, HGU was 2.8 ± 0.2, 1.0 ± 0.2, and 0.8 ± 0.2 mg·kg−1·min−1 in CTR, HFA, and HFR, respectively (P < 0.05 for HFA and HFR vs. CTR). Compared with CTR, hepatic GK protein and catalytic activity were reduced (P < 0.05) 35 and 56%, respectively, in HFA, and 53 and 74%, respectively, in HFR. Liver glycogen concentrations were 20 and 38% lower in HFA and HFR than CTR (P < 0.05). Hepatic Akt phosphorylation was decreased (P < 0.05) in HFA (21%) but not HFR. Thus, HFR impaired hepatic GK and glycogen more than HFA, whereas HFA reduced insulin signaling more than HFR. HFA and HFR effects were not additive, suggesting that they act via the same mechanism or their effects converge at a saturable step.Item Insulin Resistance Does Not Impair Mechanical Overload-Stimulated Glucose Uptake, but Does Alter the Metabolic Fate of Glucose in Mouse Muscle(MDPI, 2020-07-01) Weyrauch, Luke A.; McMillin, Shawna L.; Witczak, Carol A.; Anatomy and Cell Biology, School of MedicineSkeletal muscle glucose uptake and glucose metabolism are impaired in insulin resistance. Mechanical overload stimulates glucose uptake into insulin-resistant muscle; yet the mechanisms underlying this beneficial effect remain poorly understood. This study examined whether a differential partitioning of glucose metabolism is part of the mechanosensitive mechanism underlying overload-stimulated glucose uptake in insulin-resistant muscle. Mice were fed a high-fat diet to induce insulin resistance. Plantaris muscle overload was induced by unilateral synergist ablation. After 5 days, muscles were excised for the following measurements: (1) [3H]-2-deoxyglucose uptake; (2) glycogen; 3) [5-3H]-glucose flux through glycolysis; (4) lactate secretion; (5) metabolites; and (6) immunoblots. Overload increased glucose uptake ~80% in both insulin-sensitive and insulin-resistant muscles. Overload increased glycogen content ~20% and this was enhanced to ~40% in the insulin-resistant muscle. Overload did not alter glycolytic flux, but did increase muscle lactate secretion 40–50%. In both insulin-sensitive and insulin-resistant muscles, overload increased 6-phosphogluconate levels ~150% and decreased NADP:NADPH ~60%, indicating pentose phosphate pathway activation. Overload increased protein O-GlcNAcylation ~45% and this was enhanced to ~55% in the insulin-resistant muscle, indicating hexosamine pathway activation. In conclusion, insulin resistance does not impair mechanical overload-stimulated glucose uptake but does alter the metabolic fate of glucose in muscle.Item The regulation of glycogen metabolism in the yeast Saccharomyces cerevisiae(1997) Huang, DongqingItem Vaginal Glycogen, Not Estradiol, Is Associated With Vaginal Bacterial Community Composition in Black Adolescent Women(Elsevier, 2019-03-14) Nunn, Kenetta L.; Ridenhour, Benjamin J.; Chester, Emily M.; Vitzthum, Virginia J.; Fortenberry, J. Dennis; Forney, Larry J.; Pediatrics, School of MedicinePurpose The purpose of this study was to characterize the composition of vaginal bacterial communities in a cohort of Black adolescent women and to determine how the species composition of these communities correlate with levels of estradiol, glycogen, and stress. Methods Twenty-one Black adolescent women were sampled longitudinally. The composition of their vaginal communities was determined by analyzing the sequences of the Vl-V3 region of l6S rRNA genes and they were grouped based on patterns in species abundances. The relationships between estradiol, glycogen, psychosocial stress, and the composition of these communities were assessed. Results Vaginal communities could be distinguished and classified into three groups that differed in the abundances of Lactobacillus. Eighty-one percent of study participants had communities dominated by species of Lactobacillus. Glycogen levels were higher in communities dominated by one or multiple species of Lactobacillus as compared to those having low proportions of Lactobacillus. Estradiol and psychosocial stress measurements did not differ among the three groups, while estradiol and glycogen exhibited a weak positive relationship that was not statistically significant. Conclusions The findings of this pilot study suggest that glycogen levels are associated with vaginal community composition in young Black women; however, estradiol and psychosocial stress are not. Additionally, the results suggest there is no simple relationship between levels of estradiol and the production of vaginal glycogen.