Glycated whey proteins protect NOD mice against type 1 diabetes by increasing anti-inflammatory responses and decreasing autoreactivity to self-antigens

Abstract

Our previous studies suggested that early glycation products (EGPs) generated in the first step of Maillard reaction/glycation were anti-inflammatory. The objectives of the present study were to determine the effects of EGPs derived from the whey protein isolate-glucose system on type 1 diabetes (T1D), and the underlying immunological mechanisms. In non-obese diabetic (NOD) mice, EGPs at the physiological dose of 600 mg/kg/day increased glucose metabolism, decreased non-fasting blood glucose levels and T1D incidence, decreased insulin resistance, and decreased the pancreatic immune infiltration. The protective effects were accompanied with decreases in CD4 − CD8 + thymocytes, CD8 + T cells and serum insulin autoantibody levels, and increases in splenic CD4 + CD25 + T cells, macrophage M2/M1 ratio and serum IL-10 level. However, similar treatment with EGPs produced minimal effect on the multiple low-dose streptozotocin-induced hyperglycemia. In conclusion, EGPs protected NOD mice against T1D via increasing antiinflammatory immune responses and decreasing autoreactivity to self-antigens.

Chronic oral exposure to glycated whey proteins increases survival of aged male NOD mice with autoimmune prostatitis by regulating the gut microbiome and anti-inflammatory responses

“…No inflammation was observed for anterior and ventral prostates using histopathological analysis (data not shown). In our previous studies, however, H&E staining was shown to be less sensitive than flow cytometric analysis 9 , evidenced by the subtle differences in the immune infiltration of the pancreas being successfully detected using the latter, but not the former. Therefore, the infiltrating immune cells in the anterior prostate, after being treated for 6 months, were analyzed by flow cytometry (Fig 2C).…”

“…Age-matched non-diabetic NOD males (approximately 4-month-old) were randomly separated into 2 groups and gavaged daily with NR and EGPs at 600 mg/kg body weight (BW) for up to 6 months. This dose was physiologically relevant as discussed previously 7 , and EGPs at this dose protected NOD mice from developing T1D 9 . Mice were euthanized at month 3 and 6 following the first dosing.…”

“…In brief, whey protein isolate (WPI, Fonterra (USA) Inc, Rosemont, IL) and glucose (Sigma-Aldrich, St. Louis, MO) were dissolved in distilled water at the molar ratio of free amino groups and reducing ends at 1:2. The solution was freeze-dried and incubated in a desiccator containing a saturated aqueous Mg(NO 3 ) 2 solution at 55 °C for 8 h. LC-MS showed that all the whey proteins were modified by glucose, and the reaction had not progressed to later stages 9 .…”

“…The preparation of single-cell suspensions were similar to the procedures described before 9 . A section was dissected from the anterior prostate (AP) and placed into PBS, and digested by 0.05 mg/ml collagenase (Sigma-Aldrich) and 5 U/ml DNase (Sigma-Aldrich) at 37 °C for 30-45 min.…”

“…Our previous studies showed that whey protein derived early glycation products were able to polarize macrophages toward the anti-inflammatory M2 both in vitro 7 and in vivo 8 . Sub-chronic oral exposure to these EGPs reduced the type 1 diabetes (T1D) incidence in female non-obese diabetic (NOD) mice, and the mechanisms were through increasing anti-inflammatory responses and decreasing autoantibody generation 9 . These findings suggest EGPs are anti-inflammatory and may have potential as a functional food for patients with chronic prostatitis caused by inflammation.…”