Sources of hepatic glycogen synthesis in mice fed with glucose or fructose as the sole dietary carbohydrate

Abstract

H NMR analysis of hepatic glycogen H enrichment from H O provides realistic profiles of dietary glucose and fructose contributions to hepatic glycogen synthesis in mice fed with diets containing 1 or the other sugar as the sole carbohydrate source.

Metabolic incorporation of H218O into specific glucose‐6‐phosphate oxygens by red‐blood‐cell lysates as observed by 13C isotope‐shifted NMR signals

“…Resolution of hexose positional enrichments from 2 H-enriched water reveals both the turnover rate and contributions of specific pathways or precursors to glucose and glycogen synthesis. 1,17,18 With the exception of the Position 1 oxygen, which can exchange spontaneously albeit slowly with that of water, 19 incorporation of 18 O into Positions 2-6 of glucose-6-phosphate also informs its formation from sugar phosphate precursors via enzymatic steps. As shown in Figure 1, the hemolysate preparation mediates incorporation of 18 O from water into Positions 1, 2, 4 and 5 of glucose-6-phosphate.…”

Determining the contribution of a high-fructose corn syrup formulation to hepatic glycogen synthesis during ad-libitum feeding in mice

“…The fraction of newly synthesized glycogen and the contributions of direct pathway, indirect-Krebs cycle and indirect-triose-P sources were quantified from enrichment of glycogen positions 2, 5, 6 S and that of body water as previously described 11 , 12 . Enrichment of glycogen position 2 was corrected for incomplete exchange of body water and position 2 hydrogens by multiplication with 1.57 11 . Since direct pathway and glycogen-glucose-6-P cycling fluxes both contribute to position 2 enrichment 22 , we reported this activity as direct pathway + glycogen cycling.…”

“…In the setting of high sucrose or HFCS feeding, the effects of the fructose component on hepatic glycogen synthesis rates and on the conversion of dietary glucose to glycogen are unclear. On the one hand, fructose is a potent glycogenic precursor 11 , 12 that is converted to glycogen via the indirect pathway, thereby potentially competing with glucose for hepatic glycogen synthesis. On the other hand, fructose potentiates the conversion of glucose to glycogen via glucokinase activation 13 – 15 .…”

“…The aim of this study was to compare hepatic glycogen synthesis in mice fed with standard chow to mice where the standard chow was supplemented with a mixture of fructose and glucose in the drinking water corresponding to HFCS-55. Given the ~ 22% excess of fructose over glucose, coupled with previous studies documenting the efficient recruitment of fructose carbons for glycogen synthesis 11 , 12 , we hypothesized that the fructose component of HFCS-55 would be more efficiently converted to glycogen compared to the glucose component. By integrating deuterated water ( 2 H 2 O) measurements of hepatic glycogen sources under natural feeding conditions 9 , 11 , 12 , 18 with 13 C-tracers of the glucose and fructose present in the drinking water (Fig.…”

S-Nitrosoglutathione Reverts Dietary Sucrose-Induced Insulin Resistance

“…Rising amounts of glucose consumption are well documented as one of the major causes of insulin resistance [11]. Presently it is known that fructose intake is also a key risk factor for carbohydrate-induced insulin resistance [12,13]. Several studies have emerged in the last decade concerning insulin resistance associated to high sugar diets [14][15][16]; however, due to the variability on the time of exposure to the diet, percentage of the sugar within the diet, and initial and endpoint of the exposure, the metabolic alterations are inconsistent and lack any mechanism underlying the dysregulation observed in each case.…”