Abstract
Improvement of hyperglycemia through dietotherapy/herbal remedy is an effective approach to treating diabetes. In this study, mulberry leaf, famous for silkworm’s special food and therapeutic value without any side effects, alleviated diabetes by attenuating NEFA signaling and modulating intestinal microflora. Mulberry leaf treatment significantly reduce fasting blood-glucose and HbA1c, ameliorate the blood lipid profile and improve insulin resistance in streptozotocin-induced diabetic rats. Mechanistically, we found that mulberry leaf inhibited NEFA signaling by reducing downstream signaling in the NEFA pathway, further verified by reduced PKC and improved cellular energy homeostasis based on restored expression of PGC-1α, AK2, OXPHOS and adiponectin. Mulberry leaf treatment also restored the phyla Bacteroidetes and Proteobacteria and class Clostridia, which were associated with insulin resistance and diabetes. Our findings reveal that mulberry leaf is an edible with therapeutic potential for diabetes and may provide a novel dietotherapy/herbal remedy to the treatment of diabetes.
Highlights
The increased prevalence of diabetes has focused attention on a worldwide issue that significantly affects human health
After STZ injection, FSI significantly decreased in the high-fat diet (HFD) group (186 ± 24 pmol/L), which was similar to the normal chow group
There was no variation in the FSI level between diabetes animals and vehicle control, decreased pancreas islet β-cell function and increased insulin resistance were observed in STZ-induced diabetes rats according to the HOMA
Summary
The increased prevalence of diabetes has focused attention on a worldwide issue that significantly affects human health. Insulin resistance develops within hours of an acute increase in plasma NEFA levels in humans[13]. NEFAs are important for normal β-cell function and they potentiate insulin release in response to glucose and non-glucose secretagogues[15,16]. This might involve a mechanism that depends on protein kinase c (PKC). Accumulated evidence has suggested that the intestinal microbiota plays an important role in the pathogenesis of diabetes[17,18]. The intestinal microbiota may influence the host by affecting the body weight, bile acid metabolism, proinflammatory activity[21], insulin resistance[22], and modulation of gut hormones[23]. Therapy that modulates the intestinal microbiota may benefit glucose metabolism and improve insulin resistance in the host
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