509 research outputs found

    Characterization of Pregnancy Induced Changes in Glucose Metabolism

    Get PDF
    Many reports indicate that pregnancy is a diabetogenic state in which there is both insulin resistance and an exaggerated maternal glucose and insulin response to food ingestion. However, the magnitude of these aberrations and their temporal relationship have not been adequately characterized. This study utilizes the hyperglycemic clamp technique to investigate the insulin secretory response and tissue sensitivity to insulin under hyperglycemic conditions in normal and gestational diabetic pregnancies. Our results indicate that third trimester normal pregnancy is characterized by an increased first phase (108.81+/-13.03 uU/ml) and second phase (228.57+/-43.40 microunits/ml) insulin secretory response as compared to non-pregnant controls (72.93+/-15.76, 103.02+8/-12.43 ) (p\u3c0.05). However, C-peptide values did not mirror those of insulin in that normal pregnant women during the third trimester of pregnancy demonstrated a significantly lower C-peptide to insulin ratio than either non-pregnant controls or gestational diabetic women in their third trimester (p\u3c0.05). In contrast to normal pregnant women, gestational diabetic women in their third trimester of pregnancy showed no increase in insulin secretion. Glucose uptake under hyperglycemic conditions tended to decrease progressively through pregnancy and was significantly lower than non-pregnant controls (10. 60+/-1. 19 mg/kg/min) in the third trimester of normal pregnancy (7.20+/-0.79 mg/kg/min) and gestational diabetic pregnancy (5.87+/-0.27 mg/kg/min) (p\u3c0.05). Furthermore, there was a significantly lower tissue sensitivity to insulin (defined by the ratio of the glucose uptake to the circulating insulin level during the final sixty minutes of the study) in normal third trimester pregnancies (0.03+/-0.01 mg/kg/min per uU/ml) and gestational diabetic pregnancies (0. 04+/-0. 01 mg/kg/min per uU/ml) as compared to non-pregnant controls (0.11+/-0.02 mg/kg/min per uU/ml) (p\u3c0.05). Neither glucagon nor growth hormone were found to be significantly different between the normal pregnant or gestational diabetic groups. These studies suggest that normal pregnancy is indeed characterized by a tissue insensitivity to insulin and that glucose tolerance (defined in this study as the rate of glucose uptake) in normal pregnancy is primarily related to the degree of compensatory hyperinsulinism. However, this increased compensatory insulin secretion appears to be absent in gestational diabetic women, thereby contributing to the deterioration of glucose tolerance observed in these women

    Liability of Individuals Who Serve on Panels Reviewing Allegations of Misconduct in Science

    Get PDF

    Severe hypoxaemic hypercapnia compounds cerebral oxidative–nitrosative stress during extreme apnoea: Implications for cerebral bioenergetic function

    Get PDF
    We examined the extent to which apnoea-induced extremes of oxygen demand/carbon dioxide production impact redox regulation of cerebral bioenergetic function. Ten ultra-elite apnoeists (six men and four women) performed two maximal dry apnoeas preceded by normoxic normoventilation, resulting in severe end-apnoea hypoxaemic hypercapnia, and hyperoxic hyperventilation designed to ablate hypoxaemia, resulting in hyperoxaemic hypercapnia. Transcerebral exchange of ascorbate radicals (by electron paramagnetic resonance spectroscopy) and nitric oxide metabolites (by tri-iodide chemiluminescence) were calculated as the product of global cerebral blood flow (by duplex ultrasound) and radial arterial (a) to internal jugular venous (v) concentration gradients. Apnoea duration increased from 306 ± 62 s during hypoxaemic hypercapnia to 959 ± 201 s in hyperoxaemic hypercapnia (P ≤ 0.001). Apnoea generally increased global cerebral blood flow (all P ≤ 0.001) but was insufficient to prevent a reduction in the cerebral metabolic rates of oxygen and glucose (P = 0.015–0.044). This was associated with a general net cerebral output (v > a) of ascorbate radicals that was greater in hypoxaemic hypercapnia (P = 0.046 vs. hyperoxaemic hypercapnia) and coincided with a selective suppression in plasma nitrite uptake (a > v) and global cerebral blood flow (P = 0.034 to <0.001 vs. hyperoxaemic hypercapnia), implying reduced consumption and delivery of nitric oxide consistent with elevated cerebral oxidative–nitrosative stress. In contrast, we failed to observe equidirectional gradients consistent with S-nitrosohaemoglobin consumption and plasma S-nitrosothiol delivery during apnoea (all P ≥ 0.05). Collectively, these findings highlight a key catalytic role for hypoxaemic hypercapnia in cerebral oxidative–nitrosative stress
    • …
    corecore