Acarbose, lente carbohydrate, and prebiotics promote metabolic health and longevity by stimulating intestinal production of GLP-1

Abstract

The α-glucosidase inhibitor acarbose, which slows carbohydrate digestion and blunts postprandial rises in plasma glucose, has long been used to treat patients with type 2 diabetes or glucose intolerance. Like metformin, acarbose tends to aid weight control, postpone onset of diabetes and decrease risk for cardiovascular events. Acarbose treatment can favourably affect blood pressure, serum lipids, platelet aggregation, progression of carotid intima-media thickness and postprandial endothelial dysfunction. In mice, lifetime acarbose feeding can increase median and maximal lifespan-an effect associated with increased plasma levels of fibroblast growth factor 21 (FGF21) and decreased levels of insulin-like growth factor-I (IGF-I). There is growing reason to suspect that an upregulation of fasting and postprandial production of glucagon-like peptide-1 (GLP-1)-stemming from increased delivery of carbohydrate to L cells in the distal intestinal tract-is largely responsible for the versatile health protection conferred by acarbose. Indeed, GLP-1 exerts protective effects on vascular endothelium, the liver, the heart, pancreatic β cells, and the brain which can rationalise many of the benefits reported with acarbose. And GLP-1 may act on the liver to modulate its production of FGF21 and IGF-I, thereby promoting longevity. The benefits of acarbose are likely mimicked by diets featuring slowly-digested 'lente' carbohydrate, and by certain nutraceuticals which can slow carbohydrate absorption. Prebiotics that promote colonic generation of short-chain fatty acids represent an alternative strategy for boosting intestinal GLP-1 production. The health benefits of all these measures presumably would be potentiated by concurrent use of dipeptidyl peptidase 4 inhibitors, which slow the proteolysis of GLP-1 in the blood.

Figure 1

Potential health benefits of lente carbohydrate/acarbose. GLP, glucagon-like peptide-1; FGF21, fibroblast growth factor 21; IGF-I,  insulin-like growth factor-I; eNOS, endothelial nitric oxide synthase; FFA, free fatty acids; SCFA, short-chain fatty acids.