title: Iron deficiency decreases gluconeogenesis in isolated rat hepatocytes.
abstract: Dietary iron deficiency in rats results in increased blood glucose turnover and recycling. We measured the rates of glucose production in isolated hepatocytes from iron-sufficient (Fe+) and iron-deficient (Fe-) rats to assess the intrinsic capacity of the Fe- liver to carry out gluconeogenesis. Low-iron and control diets were given to 21-day-old female rats. After 4-5 wk, hemoglobin concentrations averaged 4.1 g/dl in the Fe- and 14.3 g/dl in the Fe+ animals. In the hepatocytes from Fe- rats, there was a 35% decrease in the rate of glucose production from 1 mM pyruvate + 10 mM lactate, a 48% decrease from 0.1 mM pyruvate + 1 mM lactate, a 39% decrease from 1 mM alanine, and a 48% decrease from 1 mM glycerol. The addition of 5 microM norepinephrine or 0.5 microM glucagon to the incubation media produced stimulatory effects on hepatocytes from both Fe- and Fe+ rats, resulting in the maintenance of an average difference of 38% in the rates of gluconeogenesis between the two groups. Studies on isolated liver mitochondria and cytosol revealed alpha-glycerophosphate-cytochrome c reductase and phospho(enol)pyruvate carboxykinase activities to be decreased by 27% in Fe- rats. We conclude that because severe dietary iron deficiency decreases gluconeogenesis in isolated rat hepatocytes, the increased gluconeogenesis demonstrated by Fe- rats in vivo is attributable to increased availability of gluconeogenic substrates and upregulation of the pathway.
authors.affiliation: Department of Physical Education, University of California, Berkeley 94720.
authors.forename: K L
authors.initials: KL
authors.lastname: Klempa
authors.forename: W T
authors.initials: WT
authors.lastname: Willis
authors.forename: R
authors.initials: R
authors.lastname: Chengson
authors.forename: P R
authors.initials: PR
authors.lastname: Dallman
authors.forename: G A
authors.initials: GA
authors.lastname: Brooks
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D003579:Cytochrome Reductases / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D004032:Diet; D005260:Female; D005934:Glucagon / Q000494:pharmacology; D005943:Gluconeogenesis; D006454:Hemoglobins / Q000378:metabolism; D066298:In Vitro Techniques; D000090463:Iron Deficiencies; D008099:Liver / Q000166:cytology / Q000378:metabolism*; D008930:Mitochondria, Liver / Q000201:enzymology; D009638:Norepinephrine / Q000494:pharmacology; D010729:Phosphoenolpyruvate Carboxykinase (GTP) / Q000378:metabolism; D011773:Pyruvates / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D011919:Rats, Inbred Strains
chemical_list: D001786:Blood Glucose; D006454:Hemoglobins; D011773:Pyruvates; D005934:Glucagon; D003579:Cytochrome Reductases; D010729:Phosphoenolpyruvate Carboxykinase (GTP); D009638:Norepinephrine