Combined Effect of Dietary Cadmium and Benzo(a)pyrene on Metallothionein Induction and Apoptosis in the Liver and Kidneys of Bank Voles

Bank voles free living in a contaminated environment have been shown to be more sensitive to cadmium (Cd) toxicity than the rodents exposed to Cd under laboratory conditions. The objective of this study was to find out whether benzo(a)pyrene (BaP), a common environmental co-contaminant, increases Cd toxicity through inhibition of metallothionein (MT) synthesis—a low molecular weight protein that is considered to be primary intracellular component of the protective mechanism. For 6 weeks, the female bank voles were provided with diet containing Cd [less than 0.1 μg/g (control) and 60 μg/g dry wt.] and BaP (0, 5, and 10 μg/g dry wt.) alone or in combination. At the end of exposure period, apoptosis and analyses of MT, Cd, and zinc (Zn) in the liver and kidneys were carried out. Dietary BaP 5 μg/g did not affect but BaP 10 μg/g potentiated rather than inhibited induction of hepatic and renal MT by Cd, and diminished Cd-induced apoptosis in both organs. The hepatic and renal Zn followed a pattern similar to that of MT, attaining the highest level in the Cd + BaP 10-μg/g group. These data indicate that dietary BaP attenuates rather than exacerbates Cd toxicity in bank voles, probably by potentiating MT synthesis and increasing Zn concentration in the liver and kidneys

Low basal metabolic rate as a risk factor for development of insulin resistance and type 2 diabetes

Introduction Identification of physiological factors influencing susceptibility to insulin resistance and type 2 diabetes (T2D) remains an important challenge for biology and medicine. Numerous studies reported energy expenditures as one of those components directly linked to T2D, with noticeable increase of basal metabolic rate (BMR) associated with the progression of insulin resistance. Conversely, the putative link between genetic, rather than phenotypic, determination of BMR and predisposition to development of T2D remains little studied. In particular, low BMR may constitute a considerable risk factor predisposing to development of T2D.Research design and methods We analyzed the development of insulin resistance and T2D in 20-week-old male laboratory mice originating from three independent genetic line types. Two of those lines were subjected to divergent, non-replicated selection towards high or low body mass-corrected BMR. The third line type was non-selected and consisted of randomly bred animals serving as an outgroup (reference) to the selected line types. To induce insulin resistance, mice were fed for 8 weeks with a high fat diet; the T2D was induced by injection with a single dose of streptozotocin and further promotion with high fat diet. As markers for insulin resistance and T2D advancement, we followed the changes in body mass, fasting blood glucose, insulin level, lipid profile and mTOR expression.Results We found BMR-associated differentiation in standard diabetic indexes between studied metabolic lines. In particular, mice with low BMR were characterized by faster body mass gain, blood glucose gain and deterioration in lipid profile. In contrast, high BMR mice were characterized by markedly higher expression of the mTOR, which may be associated with much slower development of T2D.Conclusions Our study suggests that genetically determined low BMR makeup involves metabolism-specific pathways increasing the risk of development of insulin resistance and T2D