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Query: UMLS:C0240066 (iron deficiency)
 7,156 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Newborn infants of diabetic mothers have serum biochemical signs of iron deficiency in cord blood directly related to elevations of cord erythropoietin and Hb concentrations. In sheep, chronic fetal hyperinsulinemia results in fetal hypoxemia, expansion of the red cell mass, and decreased iron concentrations, most likely due to increased iron utilization for Hb synthesis. To determine whether fetal insulin exposure also results in reduced tissue iron concentrations, we measured liver, skeletal muscle, small intestine, heart, and brain iron concentrations in newborn rat pups after s.c. fetal injection of insulin or diluent alone on d 19 of gestation. The fetuses of 11 pregnant rats were exteriorized, injected with 2 U neutral protamine Hagedorn insulin or diluent, replaced in utero, and delivered on d 22. To determine dose dependency, the fetuses of six pregnant rats were injected with 3 U of longer-acting protamine zinc insulin and delivered on d 21. At delivery, the insulin-treated groups had higher birth weights than the placebo-treated group, although plasma insulin concentrations were not different. The 2 U neutral protamine Hagedorn insulin-treated fetuses had significantly lower mean +/- SEM liver iron concentrations than the control fetuses (910 +/- 34 versus 1014 +/- 43 micrograms/g dry tissue weight; p less than 0.05), but had similar skeletal muscle iron concentrations. The 3 U protamine zinc insulin-treated fetuses had significantly lower liver and skeletal muscle iron concentrations compared to control and to 2 U neutral protamine Hagedorn insulin-treated fetuses (p less than 0.05). No differences in small intestine, heart, or brain iron concentrations were seen among groups.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The effect of in utero insulin exposure on tissue iron status in fetal rats. 159 33

Nutritional iron deficiency induced in rats causes a significant reduction in level of brain nonheme iron and is accompanied by selective reduction of dopamine D2 receptor Bmax. Our previous studies have clearly demonstrated that these alterations can be restored to normal by supplementation with ferrous sulfate; however, neither brain nonheme iron level nor dopamine D2 receptor Bmax can be increased beyond control values even after long-term iron therapy. The possibility that iron deficiency can induce the breakdown of the blood-brain barrier (BBB) was examined. A 70 and 100% increase in brain uptake index (BUI) for L-glucose and insulin, respectively, were noted in iron-deficient rats. However, the BUI for valine was decreased by 40%, and those for L-norepinephrine and glycine were unchanged. In addition, it was demonstrated that in normal rats insulin is transported into the brain. The data show that iron deficiency selectively affects the integrity of the BBB for insulin, glucose, and valine transport. Whether the effect of iron deficiency on the BBB is at the level of the capillary endothelial cell tight junction is not yet known. However, this study has shown that an important nutritional disorder (iron-deficiency anemia) has a profound effect on the BBB and brain function.
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PMID:Selective alteration in blood-brain barrier and insulin transport in iron-deficient rats. 296 35

Iron deficient (ID) and control (C) rats were studied to determine if severe iron deficiency alters insulin-stimulated glucose disposal. Euglycemic hyperinsulinemic glucose clamps were conducted by infusing insulin (2 m mu.kg-1.min-1, constant rate) for 120 min while maintaining euglycemia. In a 12-h fasted state, ID rats were hyperglycemic (109.4 +/- 4.0 mg.dL-1 arterial plasma glucose, x +/- SEM) when compared with C rats (86.9 +/- 3.4 mg.dL-1) (P less than 0.05). Even though insulin was infused identically on a per kilogram body weight basis for both groups, the resulting hyperinsulinemia was higher in ID rats (3.1 +/- 0.27 ng.mL-1) compared with C rats (2.3 +/- 0.4 ng.mL-1) at the end of the clamp. Glucose infusion rates required to maintain euglycemia were twofold higher in ID rats (27.0 +/- 5.4 mg.kg-1.min-1) versus C rats (13.1 +/- 3.3 mg.kg-1.min-1) (P less than 0.05). Circulating lactic acid increased in both groups, and the concentrations in ID rats (3.2 +/- 0.4 mmol.L-1) were significantly higher than those in C rats (1.8 +/- 0.5 mmol.L-1) at the end of the clamp. When the efficiency of insulin to dispose glucose was evaluated by calculating the glucose disposal divided by the prevailing insulinemia, ID rats could dispose of almost twice the glucose per unit of insulin [9.0 +/- 0.6 (mg.kg-1.min-1)/(ng.mL-1)] when compared with C rats [5.6 +/- 0.9 (mg.kg-1.min-1)/(ng.mL-1)] (P less than 0.05). The data indicate that insulin sensitivity is increased in ID rats and that ID rats cannot metabolize exogenous insulin as well as C rats.
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PMID:Increased insulin sensitivity in iron-deficient rats. 304 44

To evaluate the hypothesis that mild iron deficiency increases dependence upon gluconeogenesis, control and mildly iron-deficient (Hb = 80 +/- 2 g/L) rats were injected with mercaptopicolinic acid (MPA), a known inhibitor of gluconeogenesis, or with injection vehicle (sham) and studied at rest or after 30 min of treadmill running (13.4 m/min, 0% grade). Liver glycogen concentration was lower in resting iron-deficient rats than in resting control rats, but iron deficiency did not influence arterial substrates or hormones in sham-treated rats. Glucose and insulin concentrations were less in resting control and iron-deficient MPA-treated rats than in sham-treated animals. However, arterial lactate was greater in resting iron-deficient MPA-treated rats than control MPA-treated animals, and glucagon and epinephrine were greater in resting iron-deficient MPA-treated rats than in iron-deficient sham-treated animals, indicating that gluconeogenesis is more important to maintenance of euglycemia in resting iron-deficient animals than in controls. Moderate exercise stimulated glucose metabolism in iron-deficient rats, as evidenced by the lower arterial glucose and higher arterial lactate when compared with resting iron-deficient rats. However, MPA treatment did not clearly establish differences between iron-deficient and control rats after exercise. Therefore, changes in substrate and hormone concentrations in resting iron-deficient MPA-treated rats indicate that dependence on gluconeogenesis for maintenance of euglycemia is greater at rest with dietary iron deficiency. Furthermore, consistent with previously published results for severely iron-deficient rats, results from the present investigation indicate that dependence on glucose metabolism is greater during moderate exercise in mildly iron-deficient rats.
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PMID:Maintenance of euglycemia is impaired in gluconeogenesis-inhibited iron-deficient rats at rest and during exercise. 796 96

We screened for celiac disease, by means of IgA class anti-endomysium antibodies (EmA), 383 consecutive adults with insulin-dependent diabetes mellitus (IDDM). Two control populations entered the study as well: 151 adults with biopsy proven celiac disease, as true positives; and 520 controls (healthy and diseased) as true negatives. IgA-EmA positivity was found in 145 of 151 (96%) celiac disease patients but in none of the controls (100% specificity). EmA were positive in 12 of 383 (3.13%) IDDM patients: 10 of these positives underwent intestinal biopsy, which showed either partial or total villous atrophy. Only one patient presented with gastrointestinal complaints, but severe iron deficiency was found in all. The IDDM celiac patients were started on a gluten-free diet: four refused both the diet and the follow-up protocol. Approximately one year after gluten withdrawal no significant change in the degree of diabetes control was observed, while an increased requirement for insulin was observed in three of four patients who strictly complied with the diet. The prevalence of biopsy-proven celiac disease among adult IDDM patients (1:38), eight times higher than that recently estimated for the general Italian population and the absence, except in one case, of gastrointestinal symptoms emphasizes the benefit of screening programs on populations at risk.
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PMID:Celiac disease and insulin-dependent diabetes mellitus. Screening in an adult population. 805 Mar 11

To evaluate the hypothesis that lactate supply is essential to maintain euglycemia during iron deficiency, female Sprague-Dawley rats were assigned to iron-sufficient (50 mg Fe2+/kg diet, +Fe), or iron-deficient (15 mg Fe2+/kg diet, -Fe) dietary groups and were injected with a specific beta 2-adrenergic inhibitor, ICI 118,551 (1.0 mg/kg body wt). Rats were studied at rest or after 30 min of running at 13.4 m/min 0% grade. Dietary iron deficiency decreased hemoglobin concentration 38%, but resting arterial concentrations of glucose ([Glc]), lactate ([La]), or alanine ([Ala]) were unaffected. Administration of ICI 118,551 (beta 2-blockade) decreased [La] and [Glc] 52 and 32% in resting -Fe rats, respectively. beta 2-Blockade attenuated the exercise-induced rise in [La] and decreased [Glc] 31% in exercising -Fe rats. [Ala] were unaffected by iron deficiency or exercise but decreased 24 and 18% because of beta 2-blockade in resting and exercising +Fe rats. Iron deficiency depleted resting liver glycogen concentration 45%, with no additional effect of exercise or beta 2-blockade. beta-Blockade decreased arterial insulin and increased arterial glucagon concentrations in resting -Fe and +Fe rats. During exercise glucagon concentration increased significantly more in -Fe than +Fe rats. Decreased arterial [La] with a corresponding decrease in arterial [Glc] in response to beta 2-blockade support the contention that lactate supply is critical to maintenance of euglycemia in -Fe rats at rest and during exercise.
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PMID:Lactate is essential for maintenance of euglycemia in iron-deficient rats at rest and during exercise. 809 76

We hypothesized that augmented responses of glucoregulatory hormones in iron deficiency would enhance liver and muscle glycogenolysis, leading to increased gluconeogenic precursor (lactate) supply and upregulation of hepatic gluconeogenesis. Female weanling rats were randomly placed on either a mildly iron-deficient (-Fe; 15 mg Fe/kg diet) or an iron-sufficient (+Fe; 50 mg Fe/kg diet) diet for 4 wk and studied at rest and during exhaustive treadmill running. Hemoglobin was 9.0 +/- 0.2 and 13.1 +/- 0.3 g/dl in -Fe and +Fe, respectively, after 3.5 wk of dietary iron deficiency. Arterial plasma epinephrine (Epi), norepinephrine (NE), adrenocorticotropic hormone (ACTH), corticosterone, insulin, and glucagon levels were similar at rest in both groups, as were liver, gastrocnemius, and superficial and deep vastus medialis glycogen levels. Liver and kidney phosphoenolpyruvate carboxykinase (PEPCK) activities were similar in both groups. Maximum O2 consumption was decreased (22%) in -Fe. Respiratory exchange ratio (CO2 production/O2 consumption) was unaffected at rest but increased at maximum O2 consumption in -Fe. Time to exhaustion during a standardized running test (13.4 m/min, 0% grade) was decreased 45% in -Fe (63 +/- 5 vs. 116 +/- 10 min). During exercise, euglycemia was maintained in both groups, but blood lactate was elevated in -Fe. The mean net glycogen utilization during exercise was increased in liver (43%), soleus (33%), and superficial vastus medialis (106%) and decreased in the gastrocnemius (36%) in -Fe. Liver and kidney PEPCK activities were increased similarly at exhaustion in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Augmented glucoregulatory hormone concentrations during exhausting exercise in mildly iron-deficient rats. 823 58

In the absence of dietary insufficiency, iron deficiency is usually caused by chronic blood loss or intestinal malabsorption. Celiac disease is one of the most common causes of intestinal malabsorption during childhood, and its association with insulin-dependent diabetes mellitus has been previously reported. Here the authors describe an otherwise asymptomatic diabetic adolescent boy with iron deficiency anemia that was not responsive to oral iron therapy. A diagnosis of celiac disease was made based on both anti-endomysial antibody titers and small intestinal biopsy. Institution of a gluten-free diet resulted in correction of the anemia. These observations emphasize the importance of considering a diagnosis of celiac disease in patients with nonresponsive iron deficiency anemia, particularly in the setting of insulin-dependent diabetes mellitus.
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PMID:Refractory iron deficiency anemia as the primary clinical manifestation of celiac disease. 1512 5

Pregnancy, mostly because of the mitochondria-rich placenta, is a condition that favors oxidative stress. Transitional metals, especially iron, which is particularly abundant in the placenta, are important in the production of free radicals. Protective mechanisms against free radical generation and damage increase throughout pregnancy and protect the fetus, which, however, is subjected to a degree of oxidative stress. Oxidative stress peaks by the second trimester of pregnancy, ending what appears to be a vulnerable period for fetal health and gestational progress. Conditions restricted to pregnancy, such as gestational hypertension, insulin resistance and diabetes, exhibit exaggerated indications of free radical damage. Antioxidants as well as avoidance of iron excess ameliorate maternal and early fetal damage. In rats both iron deficiency and excess result in free radical mitochondrial damage. Estimates of gestational iron requirements and of the proportion of iron absorbed from different iron supplemental doses suggest that with present supplementation schemes the intestinal mucosal cells are constantly exposed to unabsorbed iron excess and oxidative stress. Unpublished work carried out in Mexico City with nonanemic women at midpregnancy indicates that 60 mg/d of iron increases the risk of hemoconcentration, low birth weight and premature birth and produces a progressive decline in plasma copper. These risks are not observed in women supplemented with 120 mg iron once or twice per week. Studies on the influence of iron supplementation schemes on oxidative stress are needed.
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PMID:Iron and oxidative stress in pregnancy. 1273 Apr 87

There is growing evidence that increases in both hematocrit and body iron stores are components of the insulin resistance syndrome. The ability of insulin and of IGF-I - whose effective activity is increased in the context of insulin resistance - to boost activity of the transcription factor hypoxia-inducible factor-1alpha (HIF-1alpha), may be at least partially responsible for this association. HIF-1alpha, which functions physiologically as a detector of both hypoxia and iron-deficiency, promotes synthesis of erythropoietin, and may also mediate the up-regulatory impact of hypoxia on intestinal iron absorption. Insulin/IGF-I may also influence erythropoiesis more directly, as they are growth factors for developing reticulocytes. Conversely, the activation of HIF-1alpha associated with iron deficiency may be responsible for the increased glucose tolerance noted in iron-deficient animals; HIF-1alpha promotes efficient glucose uptake and glycolysis - a sensible adaptation to hypoxia - by inducing increased synthesis of glucose transporters and glycolytic enzymes. Recent reports that phlebotomy can increase the efficiency of muscle glucose uptake in lean healthy omnivores are intriguing and require further confirmation. Whether increased iron stores contribute to the elevated vascular risk associated with insulin resistance is doubtful, inasmuch as most prospective studies fail to correlate serum ferritin or transferrin saturation with subsequent vascular events. However, current data are reasonably consistent with the possibility that moderately elevated iron stores are associated with increased overall risk for cancer - and for colorectal cancer in particular; free iron may play a catalytic role in 'spontaneous' mutagenesis. Thus, iron excess may mediate at least some of the increased cancer risk associated with insulin resistance and heme-rich diets. People who are insulin resistant can minimize any health risk associated with iron overload by avoiding heme-rich flesh foods and donating blood regularly.
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PMID:Hyperinsulinemia may boost both hematocrit and iron absorption by up-regulating activity of hypoxia-inducible factor-1alpha. 1459 87


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