phytoestrogens and Diabetes-Mellitus--Type-1

Daidzein (DAZ), a dominant isoflavone in various natural products such as soybeans, has been gaining attention due to the beneficial health effects (e.g., protection against cancer and diabetes) of its metabolites. Our major hypothesis was that dietary exposure to the soy phytoestrogen DAZ could modulate the immune responses toward a protective effect and lead to improved metabolic functions (such as glucose metabolism). In this study, we applied complementary mouse models, the hybrid B6C3F1 and inbred type 1 diabetes prone non-obese diabetic (NOD) mice, to investigate if DAZ exposure modulated the immune responses. The animals were orally administered DAZ at various physiological doses (2-20 mg/kg body weight) during adulthood. DAZ significantly altered the relative organ weights in female B6C3F1 mice and decreased the B cell population (represented by CD3

Topics: Animals; Antibody Formation; B-Lymphocytes; Diabetes Mellitus, Type 1; Dietary Supplements; Female; Glucose; Glycine max; Homeostasis; Immunomodulation; Isoflavones; Male; Mice; Mice, Inbred C3H; Mice, Inbred C57BL; Mice, Inbred NOD; Phytoestrogens; T-Lymphocytes

The aim of the present study was to investigate the effects of genistein (GEN) on myocardial fibrosis in type 1 diabetic rats and explore the underlying mechanisms. Rats were divided into 4 groups: Normal control (N), diabetic control (D), low‑dose GEN treatment (L) and high‑dose GEN treatment (H) groups. Following 8 weeks, the ventricular hemodynamic parameters, fasting blood glucose (FBG), heart‑weight to body‑weight ratio (HW/BW), myocardial hydroxyproline (Hyp) content, serum creatine kinase MB isozyme (CK‑MB), lactate dehydrogenase (LDH), tumor necrosis factor‑α (TNF‑α), interleukin‑1β (IL‑1β) and interleukin‑6 (IL‑6) levels were measured. The histomorphology and ultrastructure of the heart were observed. The protein expression of myocardial transforming growth factor‑β1 (TGF‑β1), mothers against decapentaplegic homolog (Smad)‑3, phosphorylated (p)‑Smad3, Smad4, collagen‑I and collagen‑III were estimated. Compared with the N group, while the cardiac function was decreased, the levels of FBG, HW/BW, Hyp content, CK‑MB, LDH, TNF‑α, IL‑1β and IL‑6 were increased in the D group. The myocardial histomorphological alterations and ultrastructure were damaged, and the protein expression of myocardial TGF‑β1, Smad3, p‑Smad3, Smad4, collagen‑I and collagen‑III were increased in the D group. Compared with the D group, there were no differences in the ventricular hemodynamic parameters, FBG and p‑Smad3 expression in the L group, while HW/BW, Hyp content, CK‑MB, LDH, TNF‑α, IL‑1β and IL‑6 levels were decreased. The myocardial histomorphological damage was alleviated and the protein expression of TGF‑β1, Smad3, Smad4, collagen‑I and collagen‑III was decreased in the L group. Compared with L group, excluding FBG, the aforementioned indices were improved in the H group. In conclusion, GEN can attenuate myocardial fibrosis in type 1 diabetic rats, and the underlying mechanisms may be associated with the reduction of CK‑MB and LDH leakage, inhibition of the inflammatory reaction, and suppression of the TGF‑β1/Smad3 signaling pathway to regulate collagen expression.

Topics: Animals; Cardiomyopathies; Collagen Type I; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 1; Fibrosis; Genistein; Heart; Hemodynamics; Male; Myocardium; Phytoestrogens; Rats; Rats, Sprague-Dawley; Smad3 Protein; Smad4 Protein; Transforming Growth Factor beta1

Topics: Animals; Blood Glucose; Diabetes Mellitus, Type 1; Feces; Female; Gastrointestinal Microbiome; Gastrointestinal Tract; Genistein; Glucose Intolerance; Homeostasis; Hyperglycemia; Insulin; Male; Mice; Mice, Inbred NOD; Phytoestrogens; Sequence Analysis, DNA

The objective of this study was to determine the effects of the phytoestrogen genistein (GEN) on the time of onset and/or the incidence of type 1 diabetes (T1D) in female nonobese diabetic (NOD) mice, when administered GEN by gavage once every day for up to 180 days. Five groups of mice (approximately 24 animals/group; 6-7 weeks of age) were included: naive control, vehicle control (25 mM Na2CO3 in water), and 3 GEN treatment groups (2 mg/kg, 6 mg/kg, and 20 mg/kg). Mice were maintained on a soy- and alfalfa-free diet (5K96) during the study and were monitored for blood glucose changes every week. When compared to the vehicle control, exposure to 2-mg/kg GEN produced significant decreases ranging from 55 to 79% in the total incidences of diabetes (blood glucose ≥ 250 mg/dl) and severe diabetes (blood glucose ≥ 400 mg/dl) starting at week 14 of the study. However, during the later stages of the study (i.e., after week 23), the 2-mg/kg dose had no effect on disease incidence. In animals treated with 6-mg/kg and 20-mg/kg GEN, significant decreases in the total incidence of diabetes were observed starting at week 16, while the incidence of severe diabetes was significantly decreased with the changes being observed initially at weeks 18 and 17 for the 6-mg/kg and 20-mg/kg GEN treatment groups, respectively. Several lines of evidence, including histopathological analysis, suggested that GEN protected the pancreas from autoimmune destruction. However, this protective effect of GEN was absent when female NOD mice were maintained on NTP-2000 rodent diet, which contained 5% soybean meal and 7.5% alfalfa meal (the total concentrations of phytoestrogens ranged between 95 and 134 mg/kg). In summary, oral dosing of GEN reduced the incidence and increased the time to onset of T1D in female NOD mice but only when fed a soy- and alfalfa-free diet.

Topics: Animals; Autoantibodies; Blood Glucose; Creatinine; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 1; Diet; Female; Genistein; Glycine max; Insulin; Kidney; Medicago sativa; Mice; Mice, Inbred NOD; Pancreas; Phytoestrogens

Phyto-oestrogens, naturally occurring phenolic, hormone-like compounds, have raised considerable interest due to their anticarcinogenic, antiatherogenic and antioxidative potential. Oxidative stress may be one of the key factors in the development of vascular complications in patients with type 1 diabetes. Here, we tested the hypothesis that high concentrations of phyto-oestrogens in serum may be associated with lower occurrence of vascular complications in these patients.. A total of 400 patients, recruited consecutively from the participant register of the nationwide FinnDiane study of type 1 diabetes and divided into four parallel groups according to the severity of their renal disease with 100 patients to each group: (i) normoalbuminuric patients, (ii) microalbuminuric patients, (iii) macroalbuminuric patients, and (iv) patients with end-stage renal disease (ESRD).. Phyto-oestrogen concentrations in serum (enterolactone, daidzein, genistein and equol) and urine (enterolactone), assessed by time-resolved fluoroimmunoassay.. Highly elevated serum concentrations of phyto-oestrogens were measured amongst patients with diabetic nephropathy, and low concentrations amongst patients without diabetic complications. The pattern was similar for all phyto-oestrogens measured, although the increase in mean serum concentrations along with the increasing severity of renal disease was steepest for enterolactone, ranging from 13 nmol L(-1) amongst women and 18 nmol L(-1) amongst men in normoalbuminuric patients to 181 and 206 nmol L(-1) in women and men, respectively, in patients with ESRD (P < 0.001 for both genders between the groups). A strong correlation between serum enterolactone and creatinine concentration was found (r = 0.60, P < 0.001).. The serum concentration of phyto-oestrogens and the severity of diabetic renal disease showed a close positive association, suggesting that phyto-oestrogens are unable to provide any major protective effect, through antioxidative or other mechanisms, on the development of diabetic renal and cardiovascular complications.

Topics: Adult; Creatinine; Diabetes Mellitus, Type 1; Diabetic Nephropathies; Female; Humans; Isoflavones; Kidney Failure, Chronic; Male; Middle Aged; Phytoestrogens; Plant Preparations