Glucose Clearance By Iron Depletion

"Glucose clearance was increased by iron depletion and decreased by
iron supplementation"

Iron depletion by deferoxamine up-regulates glucose uptake and insulin
signaling in hepatoma cells and in rat liver.
Dongiovanni P, Valenti L, Ludovica Fracanzani A, Gatti S, Cairo G,
Fargion S
Am J Pathol 2008 Mar; 172(3):738-47.

Iron depletion improves insulin resistance in patients with
nonalcoholic fatty liver disease and diabetes and also stabilizes the
hypoxia-inducible factor (HIF)-1, resulting in increased glucose
uptake in vitro. This study investigated the effect of iron depletion
by deferoxamine on insulin signaling and glucose uptake in HepG2
hepatocytes and in rat liver. In HepG2 cells, deferoxamine stabilized
HIF-1alpha and induced the constitutive glucose transporter Glut1 and
the insulin receptor. Up-regulation of insulin receptor by
deferoxamine was mimicked by the intracellular iron chelator
deferasirox and the hypoxia inducer CoCl(2) and required the HIF-1
obligate partner ARNT/HIF-1beta. Iron depletion increased insulin
receptor activity, whereas iron supplementation had the opposite
effect. Deferoxamine consistently increased the phosphorylation status
of Akt/PKB and its targets FoxO1 and Gsk3beta, which mediate the
effect of insulin on gluconeogenesis and glycogen synthesis, and up-
regulated genes involved in glucose uptake and utilization. Iron
depletion of Sprague-Dawley rats increased HIF-1alpha expression,
improved glucose clearance, and was associated with up-regulation of
insulin receptor and Akt/PKB levels and of glucose transport in
hepatic tissue. Conversely, gluconeogenic genes were not affected. In
rats with fatty liver because of a high-calorie and high-fat diet,
glucose clearance was increased by iron depletion and decreased by
iron supplementation. Thus, iron depletion by deferoxamine up-
regulates glucose uptake, and increases insulin receptor activity and
signaling in hepatocytes in vitro and in vivo.

The American journal of pathology [Am J Pathol]
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