1-Deoxynojirimycin Alleviates Insulin Resistance via Activation of Insulin Signaling PI3K/AKT Pathway in Skeletal Muscle of db/db Mice

Abstract

1-Deoxynojirimycin (DNJ) is widely used for the treatment of diabetes mellitus as an inhibitor of intestinal α-glucosidase. However, there are few reports about its effect on insulin sensitivity improvement. The aim of the present study was to investigate whether DNJ decreased hyperglycemia by improving insulin sensitivity. An economical method was established to prepare large amounts of DNJ. Then, db/db mice were treated with DNJ intravenously (20, 40 and 80 mg¨kg´1¨day´1) for four weeks. Blood glucose and biochemical analyses were conducted to evaluate the therapeutic effects on hyperglycemia and the related molecular mechanisms in skeletal muscle were explored. DNJ significantly reduced body weight, blood glucose and serum insulin levels. DNJ treatment also improved glucose tolerance and insulin tolerance. Moreover, although expressions of total protein kinase B (AKT), phosphatidylinositol 3 kinase (PI3K), insulin receptor beta (IR-β), insulin receptor substrate-1 (IRS1) and glucose transporter 4 (GLUT4) in skeletal muscle were not affected, GLUT4 translocation and phosphorylation of Ser473-AKT, p85-PI3K, Tyr1361-IR-β and Tyr612-IRS1 were significantly increased by DNJ treatment. These results indicate that DNJ significantly improved insulin sensitivity via activating insulin signaling PI3K/AKT pathway in skeletal muscle of db/db mice.

Mulberry leaves and their potential effects against cardiometabolic risks: a review of chemical compositions, biological properties and clinical efficacy

“…2011 ) and elevated glucose transporter-4 (GLUT-4) translocation (Liu et al. 2015 ) in skeletal muscles and adipose tissues. These mechanisms could explain the amelioration of insulin resistance of target tissues.…”

New Insights into the Mechanisms of Chinese Herbal Products on Diabetes: A Focus on the “Bacteria-Mucosal Immunity-Inflammation-Diabetes” Axis

“…1-Deoxynojirimycin (DNJ, Figure 4 ) and Kuwanon G (KWG, Figure 5 ) are the effective constituents of mulberry leaf, which belongs to the genus Morus of the Moraceae family. The chemical structure of DNJ is a glucose analogue with an NH group substituting for the oxygen atom of the pyranose ring [ 100 ]. Mulberry leaf, as a traditional Chinese medicine, has been used to treat fever and inflammation for thousands of years.…”

“…DNJ inhibits the glucose absorption through competitive inhibition of α -glucosidase [ 104 ]. In db/db mice, DNJ treatment improved insulin resistance via the activation of the insulin signaling PI3K/AKT pathway in skeletal muscle [ 100 ] and the activation of the PKB/GSK-3 β signaling pathway in the liver [ 105 ].…”

Physiological Effects and Organ Distribution of <i>Bacillus amyloliquefaciens</i> AS385 Culture Broth Powder Containing 1-Deoxynojirimycin in C57BL/6J Mice

“…3B). Previous study has also demonstrated the improvement of insulin resistance improvement of insulin resistance in ob/ob mice after intravenous administration of DNJ (40). There was however, notable difference in the significance level between the fasting blood glucose level (minute 0) during the OGTT (Fig.…”