Can functional oligosaccharides reduce the risk of diabetes mellitus?

Abstract

Diabetes significantly affects the life quality and length of patients with diabetes, and almost half of the 4 million people who die from diabetes are under the age of 60. Because of the increasing number of patients with diabetes and the side effects of antidiabetic drugs, the search for new dietary supplementation from natural resources, especially functional oligosaccharides, has attracted much attention among scientific researchers. Functional oligosaccharides are potential antidiabetic treatments because of their nondigestible, low-calorie, and probiotic features. The antidiabetic activity of multiple functional oligosaccharides such as fructo-oligosaccharides, galacto-oligosaccharides, and xylo-oligosaccharides has been reviewed in this paper. Molecular mechanisms involved in the antidiabetic activity of oligosaccharides have been systematically discussed from multiple perspectives, including the improvement of pancreas function, α-glucosidase inhibition, the relief of insulin and leptin resistance, anti-inflammatory effects, regulation of gut microbiota and hormones, and the intervention of diabetic risk factors. In addition, the antidiabetic effects of functional oligosaccharides through the complex gut-brain-liver axis are summarized. The concepts addressed in this review have important clinical implications, although more works are needed to confirm the antidiabetic mechanisms of functional oligosaccharides, standardize safe dose levels, and clarify their metabolism in the human body.-Zhu, D., Yan, Q., Liu, J., Wu, X., Jiang, Z. Can functional oligosaccharides reduce the risk of diabetes mellitus?

Keywords: antidiabetic activity; dietary supplementation; molecular mechanism; risk factors.

Figure 1

Molecular structures of some functional oligosaccharides. GG, polyguluronic acid; MG, heteropolymer of polymannuronic acid and polyguluronic acid; MM, polymannuronic acid; OAG, oligo-N-acetylglucosamine.

Figure 2

The regulation of glucose and lipid homoeostasis via gut microbiota. Functional oligosaccharides promote the growth of probiotics and reverse diversified composition of microbial flora. They also enhance the production of beneficial metabolites such as SCFAs, bile acids, and lactic acid. Subsequently, probiotics and their metabolism products affect glucose and lipid metabolism via numerous metabolic mechanisms. SCFAs bound to GPCRs GPR41 or GPR43 promote the expression of gut hormones such as PYY, GLP-1, and GLP-2. In peripheral tissues, insulin and glucose sensitivity are improved and gluconeogenesis is suppressed. This activation of GPCR influences the balance of lipid synthesis and lipolysis, peroxisome proliferator-activated receptor γ (PPARγ)–related differentiation, and the expression of angiopoietin-like 4. Bile acids control the production of fibroblast growth factor (FGF) 19 and GLP-1 and influence glucose homeostasis through the activation of the nuclear farnesoid X receptor and membrane-bound GPCR in the ileum. Probiotics and their metabolic products influence inflammation, oxidative stress, and intestinal permeability. Intestinal permeability is improved by the integration of gut epithelial cells, adherence to the mucosal surface, and the intestinal mucosal barrier. ZO-1, zonula occludens-1.

Figure 3

Effect of functional oligosaccharides on high blood pressure. There are 4 possible mechanisms that have been postulated to explain the ability of functional oligosaccharides to reduce the risk of hypertension, including the regulation of the ACE regulation mechanism, cholesterol metabolism, insulin resistance, and mineral absorption. Among these, functional oligosaccharides decrease the uptake of calcium in the upper GI tract by binding ionic minerals to the functional oligosaccharides and then releasing the sequestered calcium in the colon.

Figure 4

The regulation of glucose homoeostasis via the gut-brain-liver axis. The regulation of glucose homoeostasis is a complex metabolic process and involves multiple organs. Metabolic disorders caused by HFD or high-fat and high-fructose diet (HFFD) may cause the alteration of colonic pH, intestinal bacteria, and intestinal permeability, accompanied by systemic inflammation. Functional oligosaccharides stimulate the growth of probiotics such as Bifidobacterium and Lactobacillus and down-regulate the pH. They also improve the secretion of SCFAs, including lactate, butyrate, acetate, and propionate, which suppress increases in intestinal permeability and the secretion of harmful intestinal bacteria and inflammatory mediators. SCFAs are transported to the brain, liver, and other tissues and impact glucolipid metabolism. In the brain, SCFAs up-regulate the expression of PYY, GLP-1, and BDNF and down-regulate the expression of Aβ, arachidonic acid (ARA), and docosahexaenoic acid (DHA), which control appetite, anxiety, and fear and promote the development of Alzheimer’s disease. In the liver, muscle, fat, and other peripheral tissues, functional oligosaccharides play indirect or direct roles in improving glucolipid metabolism via AMPK and insulin signal pathways, lipid synthesis, and lipidolysis. Thus, functional oligosaccharides may regulate glucolipid metabolism, gut microbiota, and inflammatory responses via the gut-brain-liver axis, thereby affecting the development of nonalcoholic fatty liver disease (NAFLD), diabetes, obesity, and other metabolic syndromes. LPL, lipoptotein lipase.