Lipoperoxide concentration in erythrocytes from workers occupationally exposed to lead (mean blood lead concentration 57.1 (SD 17.6) micrograms/dl) was significantly higher than that in controls. It was not different in plasma from the two groups. The activity of superoxide dismutase (SOD) and catalase in erythrocytes from workers exposed to lead was significantly lower than that of control subjects. The effect of lead was also seen in the glutathione concentration of erythrocytes from lead exposed workers, which was reduced to 69% of that found in erythrocytes from control workers. The increase in methaemoglobin content of erythrocytes from workers exposed to lead was less than expected and not significantly different from that of controls. A positive correlation between lipoperoxide concentration in erythrocytes and lead concentration in blood and a negative correlation between glutathione concentration in erythrocytes and blood lead concentration were found. Incubation of erythrocytes for 24 hours at 37 degrees C in the presence of lead (100 micrograms/dl) produced no changes in glutathione and lipoperoxide concentrations, although there was inhibition of activity of SOD (14.3%), catalase (10.1%), and glutathione peroxidase (35.1%). A similar experiment with heparinised whole blood showed increased haemolysis with no changes in membrane lipid peroxidation of erythrocytes. It is postulated that the lowered concentration of glutathione and decreased activity of SOD, catalase, and glutathione peroxidase in erythrocytes from workers exposed to lead may play a part in the increased membrane lipid peroxidation. Furthermore, the results suggest the possibility that leucocytes, or platelets, or both, may induce haemolysis in the presence of lead.
Intrauterine (IU) malnutrition could alter pancreatic development. In this study, we describe the effects of high-fat diet (HFD) during pregnancy on fetal growth and pancreatic morphology in an ‘at risk’ animal model of metabolic disease, the glucose transporter 4 (GLUT4) heterozygous mouse (G4+/−). WT female mice mated with G4+/− males were fed HFD or control diet (CD) for 2 weeks before mating and throughout pregnancy. At embryonic day 18.5, fetuses were killed and pancreata isolated for analysis of morphology and expression of genes involved in insulin (INS) cell development, proliferation, apoptosis, glucose transport and function. Compared with WT CD, WT HFD fetal pancreata had a 2.4-fold increase in the number of glucagon (GLU) cells ( P =0.023). HFD also increased GLU cell size by 18% in WT pancreata compared with WT CD. Compared with WT CD, G4+/− CD had an increased number of INS cells and decreased INS and GLU cell size. Compared with G4+/− CD, G4+/− HFD fetuses had increased pancreatic gene expression of Igf2 , a mitogen and inhibitor of apoptosis. The expression of genes involved in proliferation, apoptosis, glucose transport, and INS secretion was not altered in WT HFD compared with G4+/− HFD pancreata. In contrast to WT HFD pancreata, HFD exposure did not alter pancreatic islet morphology in fetuses with GLUT4 haploinsufficiency; this may be mediated in part by increased Igf2 expression. Thus, interactions between IU diet and fetal genetics may play a critical role in the developmental origins of health and disease.
ABSTRACT To elucidate the distinctive regulatory mechanisms of glucose homeostasis in the skeletal muscles of broiler chickens, hexokinase (HK)I and HKII gene expressions were characterized by northern blot analysis. Chicken HKI and HKII full‐length cDNA sequences were identified and the deduced amino acid sequences were 87.4 and 85.9% identical to that of human HKI and HKII, respectively. Using reverse transcription‐polymerase chain reaction analysis, chicken HKI mRNA was detected in the skeletal muscle, brain, heart, kidney and testis. Chicken HKII mRNA was highly expressed in the skeletal muscle and heart, whereas a lower expression was observed in the liver, brain and kidney. Fasting for 48 h or refeeding for 24 h in chickens significantly increased the skeletal muscle HKI and HKII mRNA levels in contrast to unchanged or decreased expressions in mammals. The present findings suggest that HKI and HKII have a unique role in the glucose homeostasis regulatory mechanism of chicken skeletal muscles and their role in chickens is not similar to that in mammals.
Obesity induced by a high fat (HF) diet during pregnancy (P) and lactation (L) shows a sexual dimorphic response in offspring. Studies reported a metabolic benefit for female compared to male offspring. The mechanisms that determine sexual dimorphic responses are still poorly understood. This study investigates the metabolic phenotype, adipose tissue distribution and hepatic lipid metabolism in female offspring exposed to a HF diet during P/L and early adulthood. CD1 female offspring mice were exposed to either a control (C) or a HF diet during P/L and fed a regular chow after weaning for 23 wks and then re-exposed to either the C or HF diet for 19 wks. This resulted into mice exposed to the C diet during P/L and re-exposed to either the C (C-C) or HF (C-H) diet, and mice exposed to the HF diet during P/L and re-exposed to either the C (H-C) or HF (H-H) diet (n=3-5). Body weight (BW), body composition, food intake (FI), fasted blood glucose and insulin levels, intra peritoneal glucose (ipGTT) and insulin (ipITT) tolerance were measured. Mice were sacrificed at 45 wks and qRT-PCR of stearoyl-CoA-desaturase 1 (SCD-1) as a marker of lipogenesis and of caveolin-1 (CAV1) as a protective marker of hepatic steatosis was performed in liver. BW, adiposity and ipGTT and ipITT were not different between C-H and H-H. However adiposity was increased 3.0-fold in C-H compared to C-C and 2.0-fold in H-H compared to H-C, respectively (both p<0.05). FI and fasted glucose and insulin were not different between groups. Gene expression of SCD-1 was downregulated by 69% in C-H compared to C-C and by 81% in H-H compared to H-C, respectively, (both p<0.05) in liver. In contrast, hepatic CAV1 gene expression was increased 1.93-fold in H-H compared to H-C (p<0.05). These data show that female mice are protect from the deleterious programming effects of a HF diet. Moreover, mice exposed to a HF diet during P/L exhibit protective mechanisms to prevent hepatic steatosis when re-exposed to HF diet in early adulthood. Disclosure M. Kruse: None. Y. Seki: None. X. Du: None. M.J. Charron: None.
1. Glucose transporter (GLUT) proteins, one of which is the major insulin-responsive transporter GLUT4, play a crucial role in cellular glucose uptake and glucose homeostasis in mammals. The aim of this study was to identify the extent of mRNA expression of GLUT1, GLUT2, GLUT3 and GLUT8 in chickens intrinsically lacking GLUT4. 2. GLUT1 mRNA was detected in most tissues of 3-week-old broiler chickens, with the highest expression measured in brain and adipose tissue. GLUT2 was expressed only in the liver and kidney. GLUT3 was highly expressed in the brain. GLUT8 was expressed ubiquitously, with expression in kidney and adipose tissue relatively higher than that of other tissues. 3. Expression levels of GLUT isoforms 1, 3 and 8 in skeletal muscle tissue were very low compared to the other tissues tested. 4. [3H]Cytochalasin B binding assays on tissue from 3-week-old chickens showed that the number of cytochalasin B binding sites in skeletal muscle plasma membranes was higher than in liver plasma membranes. These results suggest that GLUT proteins and/or GLUT-like proteins that bind cytochalasin B are expressed in chicken skeletal muscles. 5. It is proposed that GLUT expression and glucose transport in chicken tissues are regulated in a manner different from that in mammals.
