Abstract
Type 2 diabetes mellitus (T2DM) is a common chronic metabolic disease. Accumulating evidence has demonstrated that nonalcoholic fatty liver disease (NAFLD) shares common typical features with T2DM, and they affect each other extensively. Thus, NAFLD has emerged as a novel target for T2DM prevention and care. Although Corni Fructus (CF) and its extracts have a therapeutic effect on T2DM, its effects and mechanisms on T2DM with NAFLD are far from elucidated. In this study, a mouse model of T2DM with NAFLD complication was established in ICR mice by feeding a high-fat, high-sugar (HFHS) diet and intraperitoneally injecting with a low dose of streptozotocin (STZ). Then, the effects of iridoid glycosides (IG) extracted from CF on this mouse model were investigated. We found that 4-week IG administration remarkably alleviated hyperglycemia and insulin resistance and significantly reduced inflammation, oxidative stress, and fat accumulation in the liver of T2DM with NAFLD mice. Further studies showed that IG inhibited the NF-κB but enhanced the PI3K-AKT signaling pathway. In summary, these results indicated that the IG from CF has potential therapeutic effects on T2DM with NAFLD.
Highlights
Type 2 diabetes mellitus (T2DM) is a chronic metabolic disease, and the increasing global T2DM mortality rate makes it a vital topic of medical research [1]
Among the four extracts from Corni Fructus (CF), iridoid glycosides (IG) apparently increased the body weight, decreased the blood glucose levels, elevated the glucose tolerance, and improved insulin sensitivity and lipid metabolism in T2DM mice induced by HFHS diet and STZ
IG reversed the significant increases of oral glucose tolerance test (OGTT), fasting blood glucose (FBG) (P < 0:05), AUC (P < 0:05), Fasting insulin (FINS) (P < 0:01), and HOMA-IR (P < 0:01) and decrease of insulin sensitivity index (ISI) (P < 0:01) levels in T2DM mice, and HOMA-β (P < 0:01) was potently increased to 2.0 to 2.3-fold of the DM group after the administration of different doses of IG (Figures 2(b)–2(d), Table 1)
Summary
Type 2 diabetes mellitus (T2DM) is a chronic metabolic disease, and the increasing global T2DM mortality rate makes it a vital topic of medical research [1]. Most of the prevailing T2DM are caused by unhealthy lifestyles, which lead to abnormal glucose and lipid metabolism caused by insulin deficiency and subsequent insulin resistance [2]. As one of the most common liver disorders worldwide, nonalcoholic fatty liver disease (NAFLD) has been indicated to be closely related to T2DM [3]. 20% in the general population [6], the incidence is 65%–87% in NAFLD [7]. While NAFLD is present in 20%–30% of the general population [3], it reaches an impressive prevalence of 50%–75% of patients suffering from T2DM [8]. It has been reported that improving NAFLD could reduce the incidence of T2DM, and antidiabetic drugs could potentially treat both of these disease states simultaneously [9, 10]. Taking into account NAFLD may accelerate progress in developing effective T2DM therapy strategies
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