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Review
. 2024 Jun 4;13(11):1763.
doi: 10.3390/foods13111763.

Improvement of Theaflavins on Glucose and Lipid Metabolism in Diabetes Mellitus

Shiyu Xu  1   2 , Ying Chen  1   2 , Yushun Gong  3   4
Affiliations
Review

Improvement of Theaflavins on Glucose and Lipid Metabolism in Diabetes Mellitus

Shiyu Xu et al. Foods. .

Abstract

In diabetes mellitus, disordered glucose and lipid metabolisms precipitate diverse complications, including nonalcoholic fatty liver disease, contributing to a rising global mortality rate. Theaflavins (TFs) can improve disorders of glycolipid metabolism in diabetic patients and reduce various types of damage, including glucotoxicity, lipotoxicity, and other associated secondary adverse effects. TFs exert effects to lower blood glucose and lipids levels, partly by regulating digestive enzyme activities, activation of OATP-MCT pathway and increasing secretion of incretins such as GIP. By the Ca2+-CaMKK ꞵ-AMPK and PI3K-AKT pathway, TFs promote glucose utilization and inhibit endogenous glucose production. Along with the regulation of energy metabolism by AMPK-SIRT1 pathway, TFs enhance fatty acids oxidation and reduce de novo lipogenesis. As such, the administration of TFs holds significant promise for both the prevention and amelioration of diabetes mellitus.

Keywords: black tea; dietary polyphenols; hyperglycemia; hypertriglyceridemia; insulin resistance.

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Conflict of interest statement

The authors declare no conflicts of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

Figures

Figure 1
Figure 1
The effect of TFs on glucose metabolism disorders. TFs from black tea enter intestinal epithelial cells through the OATP-MCT pathway, then induce an increase in Ca2+ concentration. The activation of Ca2+-CaMKK ꞵ-AMPK pathway and OATP-MCT pathway inhibit glucose digestion and absorption. Besides, TFs improve intestinal flora dysbiosis and damage, as well as promoting incretin secretion. In the pancreas, TFs promote β-cells proliferation and insulin secretion and inhibit α-cells proliferation and glucagon secretion, thus inhibiting circulating blood glucose levels. By increasing the insulin level and insulin receptors activity, TFs enhance insulin sensitivity. Through the Ca2+-CaMKK ꞵ-AMPK pathway, TFs promote glucose uptake and glucose utilization in liver and skeletal muscle. Along with inhibited EGP and DNL, TFs reduce lipids transportation from liver to adipose tissue. In adipose tissue, TFs inhibit the conversion of glucose to fat and thus decrease ectopic lipid deposition. TFs reduce circulating blood glucose levels, inhibit the production of secondary adverse products such as AGEs and ROS, and inhibit inflammation and oxidative stress, thereby improving glucose metabolism disorders. OATP: organic anion-transporting polypeptides; MCT: monocarboxylic transporter; EGP: endogenous glucose production; DNL: de novo lipogenesis. A solid line and the orange color indicate enhancement; a dashed line and the blue color indicate suppression.
Figure 2
Figure 2
The effect of TFs on lipids metabolism disorders. TFs extracted from black tea inhibit lipids digestion and absorption, decrease endotoxin secretion, and increase incretin levels. By inhibiting lipid peroxides accumulation and lowering lipotoxicity, TFs improve pancreatic functions and thus increase insulin secretion. Through LKB1 and ROS pathways, TFs induce the activation of AMPK-SIRT1-PGC pathway, thereby lowering lipids levels by improving mitochondrial biosynthesis and enhancing energy consumption in the muscle and liver. The activation of SIRT1 inhibits SREBP-1, promotes FA oxidation, and reduces DNL, cholesterol accumulation, and fat mobilization in liver and adipose tissue, thereby decreasing circulating lipids levels and ectopic lipid deposition. DNL: de novo lipogenesis. A solid line and the orange color indicate enhancement; a dashed line and the blue color indicate suppression.
Figure 3
Figure 3
The effects of TFs on glucose and lipid metabolism disorders. TFs extracted from black tea inhibit digestion and absorption and increase incretin levels. Through the blood cycle, TFs increase mitochondrial biosynthesis and thus enhance energy consumption. In liver, TFs promote glucose utilization and FA oxidation. By decreasing EGP, lipids synthesis, cholesterol accumulation, fat mobilization, etc., TFs show the hypoglycemic and hypolipidemic effects. What is more, TFs improve pancreatic functions by lowering glucotoxicity and lipotoxicity, thereby increasing the insulin levels and inhibiting insulin resistance. TFs exert anti-hyperglycemia, anti-hyperlipidemia, and anti-obesity properties, and have potential as a dietary supplement for improving disorders of glucose and lipid metabolism. The blue arrowhead indicates inhibition by TFs, and red one indicates enhancement by TFs.
Figure 4
Figure 4
TFs affect glucose-lipid metabolism-related proteins and hormones. PL: pancreatic lipase; AGH: α-glucosidase; TJ: tight junction protein; ASBT: apical sodium-dependent bile acid transporter; HL: hepatic lipase; PGC-1: proliferator-activated receptor-γ coactivator-1; UPC: uncoupling protein; Sp1: specificity protein 1; CPT1: carnitine palmitoyl transferase 1; FAS: fatty acid synthase; ACC: acetyl-CoA carboxylase; HMGCR: HMG-CoA reductase; HK: hexokinase; PK: pyruvate kinase. GP: glycogen phosphorylase; GS: glycogen synthase; “*” means more research is still needed. A solid line and the red arrowhead indicate enhancement; a dashed line and the blue arrowhead indicate suppression.
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