Insulin is a protein hormone primarily involved in glucose and nutrient homeostasis. Insulin is produced by the β-cells of the pancreatic islets of Langerhans
[1][2][3]. In response to elevated blood glucose levels, following a meal, the β-cells release insulin into the circulation to be transported to its target tissues, including skeletal muscle, adipocytes, and hepatocytes
[1][2][3]. Insulin increases glucose uptake by skeletal muscle and adipose tissue, while it suppresses the endogenous production of glucose by the liver resulting in a reduction/restoration of blood glucose back to normal levels
[1][2][3].
Insulin initiates its mechanism of action through binding to its receptor located on the plasma membrane of its target cells. Insulin binding to its receptor leads to increased receptor tyrosine kinase activity, phosphorylation of the insulin receptor substrate (IRS), and downstream activation of the lipid kinase phosphatidylinositol-3 kinase (PI3-K) and the serine/threonine kinase Akt/PKB
[2][3][4]. In adipose and muscle cells, this leads to downstream glucose transporter (GLUT4) translocation from an intracellular compartment to plasma membrane and entry of glucose, while in liver cells, the result is suppression of glycogenolysis and gluconeogenesis and reduced endogenous glucose production
[3]. Impairments in insulin signaling leads to insulin resistance, and type 2 diabetes mellitus (T2DM)
[2][3][4].
Insulin resistance is a condition characterized by reduced responsiveness of target tissues to normal circulating levels of insulin
[2][4][5]. Insulin resistance/T2DM is associated with inflammation, obesity, aging and a sedentary lifestyle and results in chronic elevations of plasma glucose levels, known as hyperglycemia, that can lead to long-term complications including macrovascular and microvascular damage, cardiovascular disease, retinopathy, neuropathy, and nephropathy
[2][4][5][6][7][8][9]. Obesity is strongly linked to insulin resistance and excess plasma free-fatty acids (FFA) have been established to impair the ability of insulin to suppress hepatic glucose output and to stimulate glucose uptake by skeletal muscle
[7][9]. Furthermore, strong evidence have established that chronic inflammation contributes to insulin resistance. Pro-inflammatory cytokines such as, tumor necrosis factor-α (TNF-α), reduce the insulin-stimulated tyrosine phosphorylation of the insulin receptor and IRS-1, impairing insulin action and inducing insulin resistance
[10]. T2DM accounts for 90%–95% of all diabetes cases
[2]. The global burden of diabetes continues to rise and resulted in 5 million deaths in 2017, in the 20+ age demographic, compared to 665,000 deaths in 1990
[11]. Additionally, it is estimated that approximately 451 million people, aged 18+ are living with diabetes worldwide
[11]. Diabetic complications such as diabetic foot and diabetic neuropathy significantly increased by 47.1% and 62.6%, respectively, from 2001 to 2014
[12], and overall the rise of diabetes cases exerts a significant economic burden on the health care systems globally
[13][14]. For example, an incidence predictive study on the cost of diabetes in Canada over 10 years has estimated 2.16 million new cases of diabetes occurring during this timeframe, which is accompanied by a health care costs of $15.36 billion due to acute hospitalizations and prescription medications
[15].
Epidemiological studies have suggested that diets high in fruits and vegetables help regulate body weight and protect against chronic diseases such as cardiovascular disease, cancer, and diabetes
[16][17][18]. However, the role the individual components of these foods play in disease prevention and treatment is difficult to determine. Specific components, known as polyphenols, have increasingly gained attention within the scientific community for their potential health benefits and preventive and therapeutic properties against chronic diseases
[13][14][19][20][21][22].
Polyphenols have been established to have antioxidant properties
[23] and possess a variety of other specific biological effects such as regulating enzymes and, therefore, may prevent diseases through mechanisms that are both dependent and independent of their antioxidant properties
[24][25][26].