Select Polyphenol-Rich Berry Consumption to Defer or Deter Diabetes and Diabetes-Related Complications

Abstract

Berries are considered "promising functional fruits" due to their distinct and ubiquitous therapeutic contents of anthocyanins, proanthocyanidins, phenolic acids, flavonoids, flavanols, alkaloids, polysaccharides, hydroxycinnamic, ellagic acid derivatives, and organic acids. These polyphenols are part of berries and the human diet, and evidence suggests that their intake is associated with a reduced risk or the reversal of metabolic pathophysiologies related to diabetes, obesity, oxidative stress, inflammation, and hypertension. This work reviewed and summarized both clinical and non-clinical findings that the consumption of berries, berry extracts, purified compounds, juices, jams, jellies, and other berry byproducts aided in the prevention and or otherwise management of type 2 diabetes mellitus (T2DM) and related complications. The integration of berries and berries-derived byproducts into high-carbohydrate (HCD) and high-fat (HFD) diets, also reversed/reduced the HCD/HFD-induced alterations in glucose metabolism-related pathways, and markers of oxidative stress, inflammation, and lipid oxidation in healthy/obese/diabetic subjects. The berry polyphenols also modulate the intestinal microflora ecology by opposing the diabetic and obesity rendered symbolic reduction of Bacteroidetes/Firmicutes ratio, intestinal mucosal barrier dysfunction-restoring bacteria, short-chain fatty acids, and organic acid producing microflora. All studies proposed a number of potential mechanisms of action of respective berry bioactive compounds, although further mechanistic and molecular studies are warranted. The metabolic profiling of each berry is also included to provide up-to-date information regarding the potential anti-oxidative/antidiabetic constituents of each berry.

Keywords: berries; diabetes; genomics; hyperglycemia; hyperlipidemia; metabolic syndrome; metabolomics; omics; precision nutrition.

Figure 1

Schematic representation of Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flow diagram collection and selection of studies included in this review. Adapted from Moher, Liberati [8].

Figure 2

Schematic presentation of chokeberry anthocyanin-induced insulin secretion and antioxidant enzyme pathways in pancreatic β-cells under high-glucose-induced stress conditions. Glucose is transported across the cell membrane via glucose transporter (i.e., GLUT-2), followed by glycolysis and pyruvate production. Afterward, pyruvate is used for the generation of ATP in mitochondria. Here, in connection with the electron transport chain, radicals, like superoxide anion (O₂^•‒), are also produced and simultaneously neutralized by the enzymatic antioxidant SOD. SOD converts the O₂^•‒ into harmless O₂ and another radical H₂O₂. In addition to H₂O₂ diffusion through the cell membrane, H₂O₂ is also scavenged by CAT and GPx resulting in water and oxygen production. Chokeberry-derived anthocyanins strengthen this inherent enzymatic antioxidant system (i.e., SOD, CAT, and GPx), which can more actively neutralize the radicals generated during glucose metabolism. H₂O₂-stimulated reduction of GSH is also ameliorated by chokeberry anthocyanins. Chokeberry anthocyanins also replenish the pool of insulin by increasing the insulin gene expression. Proinsulin, a precursor of insulin, folded in the endoplasmic reticulum, is transported to the Golgi apparatus. Chokeberry anthocyanins can also influence the opening of the voltage-gated Ca²⁺ channels, leading to an increased fusion of insulin granules with the cell membrane (Source: Rugina et al. [316]).