Abstract

Proanthocyanidins are the major active compounds extracted from Iris lactea Pall. var. Chinensis (Fisch.) Koidz (I. lactea). Proanthocyanidins exhibit a variety of pharmacological activities such as anti-oxidation, anti-inflammation, anti-tumor, and lowering blood lipids. However, the underlying mechanism of its regulating effect on lipid metabolism in diabetic conditions remains unclear. The present study investigated the effects of I. lactea-derived proanthocyanidins on lipid metabolism in mice of type 2 diabetes mellitus (T2DM). Results demonstrated a beneficial effect of total proanthocyanidins on dysregulated lipid metabolism and hepatic steatosis in high-fat-diet/streptozocin (STZ)-induced T2DM. To identify the mechanisms, six flavan-3-ols were isolated from proanthocyanidins of I. lacteal and their effects on adipogenesis and dexamethasone (Dex)-induced mitochondrial dysfunctions in 3T3-L1 adipocytes were determined. In vitro studies showed flavan-3-ols inhibited adipogenesis and restored mitochondrial function after Dex-induced insulin resistance, being suggested by increased mitochondrial membrane potential, intracellular ATP contents, mitochondrial mass and mitochondrial biogenesis, and reduced reactive oxygen species. Among the six flavan-3-ols, procyanidin B3 and procyanidin B1 exhibited the strongest effects. Our study suggests potential of proanthocyanidins as therapeutic target for diabetes.

Highlights

  • Diabetes mellitus (DM), characterized by hyperglycemia and deficits in insulin secretion or action, is one of the major chronic metabolic disorders [1]

  • It has been reported that mitochondrial dysfunction plays important roles in insulin resistance and type 2 diabetes mellitus (T2DM) [31]. To further demonstrate their treatment effects on T2DM, we evaluated the protective effect of flavan-3-ols on mitochondrial functions in Dex-treated 3T3-L1 adipocytes

  • We investigated the effects of proanthocyanidins-derived flavan-3-ols on metabolism of cultured adipocytes

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Summary

Introduction

Diabetes mellitus (DM), characterized by hyperglycemia and deficits in insulin secretion or action, is one of the major chronic metabolic disorders [1]. It is estimated that about 700 million people worldwide will have diabetes by the mid of this century [2]. Most diabetic patients are type 2 diabetes mellitus (T2DM), with a major cause of deficient insulin signaling or insulin resistance [3]. It is well characterized that hyperglycemia exacerbates complications of diabetes [4]. Hyperlipidemia is regarded as one of the main risk factors of T2DM. Hyperlipidemia is a result of dysregulated hepatic lipid metabolism, which abnormally increases triglyceride (TG)

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