Iron deficiency decreases gluconeogenesis in isolated rat hepatocytes.
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.
Klempa
K L
KL
Department of Physical Education, University of California, Berkeley 94720.
Willis
W T
WT
Chengson
R
R
Dallman
P R
PR
Brooks
G A
GA
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
D001786:Blood Glucose; D006454:Hemoglobins; D011773:Pyruvates; D005934:Glucagon; D003579:Cytochrome Reductases; D010729:Phosphoenolpyruvate Carboxykinase (GTP); D009638:Norepinephrine