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Beneficial effects of combined phloretin and metformin therapy in streptozotocin-induced diabetic rats and improved insulin sensitivity in vitro

Abstract

The GLUT4 and PI3K/AKT signaling pathways are the key sensors of energy status and regulate glucose and lipid metabolism. Phloretin activates the PI3K/AKT pathway by promoting GLUT4 translocation and expression, thereby improving glucose consumption and tolerance. As metformin can regulate glucose metabolism, we hypothesized that phloretin can amplify its gluco-regulatory effects. Male Sprague Dawley rats were fed with high-fat and high-sugar diet for 8 weeks and injected with low dose of streptozotocin to induce type 2 diabetes. The diabetic rats were randomized to receive phloretin (100 mg/kg/d), metformin (250 mg/kg/d), or phloretin + metformin via oral gavage for another 4 weeks. Random blood glucose, and serum insulin, free fatty acid, total cholesterol, triglyceride, and low-density lipoprotein levels were detected in type 2 diabetic rats. Hematoxylin-eosin and Oil Red O staining were used to observe the pathological changes in the liver, pancreas, and adipose tissues of type 2 diabetic rats. The expression levels of IRS-1, PI3K, P-AKT, and GLUT4 in skeletal muscle were detected using western blotting. Phloretin plus metformin improved fasting blood glucose levels, glucose tolerance, and insulin sensitivity in type 2 diabetic rats. In addition, this combination reduced lipid accumulation, improved the pathological changes in the liver, pancreas, and adipose tissue, and increased IRS-1, PI3K, P-AKT, and GLUT4 expression in skeletal muscle and liver of type 2 diabetic rats. Thus, phloretin can be used in a potential combination therapy with metformin for the prevention and rescue of type 2 diabetes.

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Publication details

The article was received on 20 Jun 2019, accepted on 02 Dec 2019 and first published on 03 Dec 2019


Article type: Paper
DOI: 10.1039/C9FO01326A
Food Funct., 2019, Accepted Manuscript

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    Beneficial effects of combined phloretin and metformin therapy in streptozotocin-induced diabetic rats and improved insulin sensitivity in vitro

    X. Shen, L. Wang, N. Zhou, S. Gai, X. Liu and S. Zhang, Food Funct., 2019, Accepted Manuscript , DOI: 10.1039/C9FO01326A

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