Mulberry-Derived 1-Deoxynojirimycin Prevents Type 2 Diabetes Mellitus Progression via Modulation of Retinol-Binding Protein 4 and Haptoglobin.

Pre-diabetic or early-stage type 2 diabetes patients may develop an adverse diabetic progression, leading to several complications and increasing hospitalization rates. Mulberry leaves, which contain 1-deoxynojirimycin (DNJ), have been used as a complementary medicine for diabetes prevention and treatment. Our recent study demonstrated that mulberry leaf powder with 12 mg of DNJ improves postprandial hyperglycemia, fasting plasma glucose, and glycated hemoglobin. However, the detailed mechanisms are still unknown. This study investigates the effect of long-term (12-week) supplementation of mulberry leaves in obese people with prediabetes and patients with early-stage type 2 diabetes. Participants' blood was collected before and after supplementation. The protein profile of the plasma was examined by proteomics. In addition, the mitochondrial function was evaluated by energetic and homeostatic markers using immunoelectron microscopy. The proteomics results showed that, from a total of 1291 proteins, 32 proteins were related to diabetes pathogenesis. Retinol-binding protein 4 and haptoglobin protein were downregulated, which are associated with insulin resistance and inflammation, respectively. For mitochondrial function, the haloacid dehalogenase-like hydrolase domain-containing protein 3 (HDHD-3) and dynamin-related protein 1 (Drp-1) displayed a significant increment in the after treatment group. In summary, administration of mulberry leaf powder extract in prediabetes and the early stage of diabetes can alleviate insulin resistance and inflammation and promote mitochondrial function in terms of energy production and fission.