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Articles in PresS, published online ahead of print May 21, 2002
Am J Physiol Endocrinol Metab, 10.1152/ajpendo.00120.2002
Submitted on March 20, 2002
Accepted on May 19, 2002
1 Exercise Science Research Institute, Arizona State University, Tempe, AZ, USA
2 Medicine, University of Colorado Health Sciences Center, Denver, CO, USA; Exercise Science Research Institute, Arizona State University, Tempe, AZ, USA
* To whom correspondence should be addressed. E-mail: mike.pagliassotti{at}uchsc.edu.
High fat (HFD) and high sucrose (HSD) diets reduce insulin suppression of glucose production in vivo, increase the capacity for gluconeogenesis in vitro and increase glucose-6-phosphatase (G6Pase) activity in whole cell homogenates. The present study examined the effects of HSD and HFD on in vivo gluconeogenesis, the catalytic and G6P translocase subunits of G6Pase, glucokinase (GK) translocation and glucose cycling. Rats were fed a high starch control diet (STD, 68% corn starch), HSD (68% sucrose), or HFD (45% fat) for 7-13 days. The ratio of 3H in C6:C2 of glucose following 3,H2O injection into 6-8h fasted rats was significantly increased in HSD (0.68±0.07) and HFD (0.71±0.08) vs STD (0.40±0.10). G6Pase activity was significantly higher in HSD and HFD vs STD in both intact and disrupted liver microsomes. HSD and HFD significantly increased the amount of the p36 catalytic subunit protein, whereas the p46 glucose-6-phosphate translocase protein was increased in HSD only. Despite increased non-glycerol gluconeogenesis and increased G6Pase, basal glucose and insulin levels, as well as glucose production, were not significantly different among groups. Hepatocyte cell suspensions were used to ascertain whether diet-induced adaptations in glucose phosphorylation and GK might serve to compensate for upregulation of G6Pase. Tracer-estimated glucose phosphorylation and glucose cycling (glucose <--> G6P) were significantly higher in cells isolated from HSD only. Following incubation with either 5 or 20 mM glucose and no insulin, GK activity (nmol*mg protein-1*min-1) in digitonin-treated eluates (translocated GK) was significantly higher in HSD (32±4 and 146±6) vs HFD (4±1 and 83±10) and STD (9±2 and 87±9). Thus short-term, chronic exposure to diets enriched in sucrose or fat increase in vivo gluconeogenesis and the G6Pase catalytic subunit. Exposure to sucrose-enriched diets also leads to adaptations in glucose phosphorylation and glucokinase translocation.
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