IL-6 induced enhanced clearance of proANP and ANP by insulin-degrading enzyme in T1DM mice.

Cardiovascular disease (CVD) is a prevalent cause of morbidity and mortality in type I diabetes mellitus (T1DM). However, the pathophysiological mechanisms underlying the relationship between CVD, CVD risk factors, and T1DM have not yet been sufficiently explored. Here, we report that insulin-degrading enzyme (IDE) effectively degrades the precursor of atrial natriuretic peptide (proANP) in HEK293T cells. The pro-inflammatory cytokine IL-6 elicited a significant dose-dependent increase in IDE protein expression. Inhibition of the ERK/MAPK signaling pathway with selumetinib abolished the IL-6-stimulated increase in IDE protein levels and decreased ANP secretion in H9C2 cells. Importantly, the T1DM mouse model displayed lower proANP in the heart and ANP in serum, due to increased IDE expression and activity. Our results suggest a novel role of IL-6 in ANP metabolism via IDE and provide possibilities for new potential therapeutic strategies for diabetes-related cardiovascular complications.

Hypoglycemic and Hypolipidemic Activity of Polygonatum sibiricum Fermented with Lactobacillus brevis YM 1301 in Diabetic C57BL/6 Mice.

Polygonatum sibiricum (PS) has been used as herbal medicine to treat type 2 diabetes mellitus (T2DM). However, how lactic acid fermentation of PS influences glucose and lipid metabolism remains unclear. The current study was undertaken to evaluate the hypoglycemic and hypolipidemic effects of PS fermented with Lactobacillus brevis YM 1301 (YM 1301) in streptozotocin and high-fat diet-induced T2DM mice. Biochemical analysis revealed that supplementation with metformin, PS, or fermented Polygonatum sibiricum (FPS) lowered the fasting blood glucose, insulin, total cholesterol, triglyceride, and low-density lipoprotein cholesterol of diabetic mice. FPS showed relatively more potency to reduce the homeostasis model assessment-insulin resistance and glycated hemoglobin than PS. Moreover, a high dosage of FPS protected against glucose intolerance and insulin resistance by increasing the ratio of phosphor-AKT/AKT. Histological examination and quantitative polymerase chain reaction results showed that dietary FPS ameliorated the lipid accumulation in liver and white adipose tissue (WAT) by inhibiting lipogenesis, enhancing lipolysis, and fatty acid oxidation. FPS exhibited greater efficacy than PS on improving the transcriptional expression of adipose triacylglyceride lipase, carnitine palmitoyltransferase 1, and uncoupling protein 1. In addition, FPS exerted a striking anti-inflammatory effect by suppressing the expression of interleukin 6, interleukin 1ß, tumor necrosis factor-α, and transforming growth factor-ß in WAT of diabetic C57BL/6 mice. Finally, FPS supplementation enhanced the activation of AMPK. In conclusion, these results suggest that the FPS may be more promising than PS as a potential therapeutic agent for diabetes and obesity.