Colonic glucose

Colonic glucose refers to the monosaccharide glucose present in the large intestine, where it serves as a critical metabolic substrate and signaling molecule in the gut-liver-brain axis [2, 11]. While most dietary glucose is absorbed in the small intestine, pharmacological agents like metformin and SGLT1/2 inhibitors can increase the concentration of glucose in the colonic lumen by either promoting its excretion or preventing its proximal absorption [11, 17]. Once in the colon, glucose is fermented by the resident microbiota into short-chain fatty acids (SCFAs) such as butyrate and propionate, which activate G-protein-coupled receptors (e.g., GPR41/43) on colonic L-cells to stimulate the secretion of glucagon-like peptide-1 (GLP-1) and peptide YY (PYY) [3, 10, 13]. These hormones play vital roles in systemic glycemic control and satiety, making 'colonic glucose uptake' (CGU) a key biomarker for evaluating the metabolic efficacy of antidiabetic drugs via 18F-FDG PET imaging [8, 16]. Additionally, colonic glucose metabolism is a significant factor in colorectal cancer, where malignant cells undergo metabolic reprogramming to utilize glucose for rapid proliferation [1]. However, high luminal glucose levels can lead to therapeutic challenges, including osmotic diarrhea and gastrointestinal distress due to rapid microbial fermentation [6, 11].

Other names

Colonic glucose uptakeIntestinal glucoseLuminal glucoseColonic glucose disposalCGU

Drugs targeting this pathway promote the disposal of glucose into the colon or inhibit its absorption in the small intestine, leading to colonic glucose accumulation, microbial fermentation into short-chain fatty acids (SCFAs), and the subsequent triggering of GLP-1 and PYY secretion from L-cells.