Lactoferrin improves hepatic insulin resistance and pancreatic dysfunction in high-fat diet and streptozotocin-induced diabetic mice.

Lactoferrin (Lf) is an iron-binding glycoprotein with potentially beneficial biological functions. However, the interaction between Lf and type 2 diabetes mellitus (T2DM) remains unclear. We hypothesized that Lf would improve hepatic insulin resistance and pancreatic dysfunction in diabetic mice. Male C57BL/6J mice were fed a high-fat diet for 15 weeks and injected with streptozotocin (STZ) for 5 consecutive days to establish a T2DM model. One week after STZ injection, mice with ≥11.1 mmol/L fasting blood glucose concentration were considered T2DM mice. These mice received 0.5% or 2% Lf solution for another 12 weeks. Biochemical parameters were measured, and histopathological examination of the pancreas and liver was performed. Hepatic protein expression related to the insulin signalling pathway was also assessed. Diabetic mice showed insulin resistance and abnormal glucolipid metabolism. Lf decreased serum concentrations of glycated serum protein, fasting insulin, cholesterol, and triglyceride and increased liver insulin sensitivity. Hematoxylin-eosin staining showed that Lf reversed the abnormal pancreatic islets of diabetic mice. Lf improved pancreatic dysfunction by reducing oxidative stress and inflammation responses. Furthermore, Lf upregulated the protein expression of insulin receptor, insulin receptor substrate-1, glucose transporter 4, phosphor phosphatidylinositol 3-kinase/phosphatidylinositol 3-kinase (PI3K), and phosphor protein kinase B/protein kinase B (AKT) in the liver. This study indicated that Lf supplementation improved hepatic insulin resistance and pancreatic dysfunction, possibly by regulating the PI3K/AKT signaling pathway in T2DM mice.

Effectiveness and safety of Bifidobacterium and berberine in human hyperglycemia and their regulatory effect on the gut microbiota: a multi-center, double-blind, randomized, parallel-controlled study.

BACKGROUND: Berberine and Bifidobacterium have been reported to improve glucose tolerance in people with hyperglycemia or other metabolic disorders. This study aimed to assess the hypoglycemic effect and the regulation of the gut microbiota caused by berberine and Bifidobacterium and the possible additive benefits of their combination. METHODS: This was an 18-week, multi-center, randomized, double-blind, parallel-controlled study of patients newly diagnosed with hyperglycemia. After a 2-week run-in period, 300 participants were randomly assigned to the following four groups for 16 weeks of treatment: berberine (Be), Bifidobacterium (Bi), berberine and Bifidobacterium (BB), and placebo group. The primary efficacy endpoint was the absolute value of fasting plasma glucose (FPG) compared with baseline after 16 weeks of treatment. RESULTS: Between October 2015 and April 2018, a total of 297 participants were included in the primary analysis. Significant reductions of FPG were observed in the Be and BB groups compared with the placebo group, with a least square (LS) mean difference of - 0.50, 95% CI [- 0.85, - 0.15] mmol/L, and - 0.55, 95% CI [- 0.91, - 0.20] mmol/L, respectively. The Be and BB groups also showed significant reductions in 2-h postprandial plasma glucose. A pronounced decrease in HbA1c occurred in the BB group compared to the placebo group. Moreover, compared with the Bi and placebo groups, the Be and BB groups had more changes in the gut microbiota from the baseline. CONCLUSIONS: Berberine could regulate the structure and function of the human gut microbiota, and Bifidobacterium has the potential to enhance the hypoglycemic effect of berberine. These findings provide new insights into the hypoglycemic potential of berberine and Bifidobacterium. TRIAL REGISTRATION: ClinicalTrials.gov , NCT03330184. Retrospectively registered on 18 October 2017.