Anti-inflammatory effects of grape seed procyanidin B2 on a diabetic pancreas

Abstract

The prevalence of type 2 diabetes mellitus (T2DM) has increased considerably in recent years, highlighting the importance of developing new therapeutic strategies. Insulin-resistance and gradual dysfunction of pancreatic islets are the mainstay in the progression of T2DM. Therefore, preserving the function of the pancreas may lead to new prospective approaches. Our previous studies suggested that grape seed procyanidin B2 (GSPB2), a natural polyphenol product, exhibited protective effects on diabetic vasculopathy. However, effects of GSPB2 on a diabetic pancreas remain unknown. In this study, we provided strong evidence that GSPB2 exerted protective effects on a diabetic pancreas. GSPB2 attenuated the elevated body weights, food intake and advanced glycation end-product (AGE) levels in db/db mice (p < 0.05), though it had no significant effect on glucose levels. The increased islet sizes, insulin levels, as well as HOMA-IR were also improved by GSPB2 treatment in db/db mice (p < 0.05). Milk fat globule epidermal growth factor-8 (MFG-E8), an estimated target of GSPB2 in our previous studies, was up-regulated in pancreatic tissues whereas GSPB2 treatment down-regulated the protein level (p < 0.05). Since MFG-E8 is highly involved in inflammation, we further investigate pro-inflammatory cytokines interleukin-1β (IL-1β) and NLRP3 levels. We found that levels of IL-1β and NLRP3 increased in a diabetic pancreas while GSPB2 treatment notably attenuated these alterations (p < 0.05). In conclusion, our results suggest that inflammation is involved in the damage of a diabetic pancreas and GSPB2 provides protective effects at least in part through anti-inflammation.

Elevated serum milk fat globule‐epidermal growth factor 8 levels in type 2 diabetic patients are suppressed by overweight or obese status

“…To date, the upregulation of MFG‐E8 levels has been reported in db/db mice, as well as patients with T2D and chronic pancreatitis . The current investigation presented supporting evidence for the concept that T2D patients had higher MFG‐E8 serum levels than healthy controls.…”

Circulating milk fat globule‐epidermal growth factor 8 levels are increased in pregnancy and gestational diabetes mellitus

“…This suggests a similarity in alteration in MFG‐E8 activity that was found in the myometrium, as well as in the endometrium during human pregnancy, which was probably due to MFG‐E8 functioning as an extracellular growth factor during gestation that promoted expansion of the connective tissue framework supporting the hypertrophied bundles of smooth muscle. Furthermore, we established that the plasma concentrations of MFG‐E8 were greater in GDM than that observed in normal pregnant women, which was in consist with the elevated MFG‐E8 levels that have been confirmed in db / db mice and type 2 diabetes patients. However, the exact mechanism of elevated MFG‐E8 concentrations during human gestation and GDM has not been completely elucidated yet, and further research is required for it to be clearly understood.…”

Anti-Diabetic Effects of the Ethyl-Acetate Fraction of Trichilia catigua in Streptozo-tocin-Induced Type 1 Diabetic Rats

“…On the other hand, recent studies have shown antiinflammatory and antioxidant effects of PB2 and EPC, which exert positive effects by improving diabetes comorbidities. They were observed to bring improvement in insulin sensitivity and to exert a protective effect against diabetic nephropathy and cardiomyopathy [20,21].…”