Hyperglycemia-Induced Alterations in Colonic Motility and Secretion: Roles of 5-Hydroxytryptamine Signaling and Translational Implications

Diabetes mellitus is frequently associated with gastrointestinal dysfunction, traditionally linked to gastric dysmotility. Recent evidence demonstrates that chronic hyperglycemia also disrupts colonic motility and epithelial secretion, contributing to constipation, diarrhea, and fecal incontinence. Experimental studies using streptozotocin-induced hyperglycemia reveal impaired coordination between smooth muscle contractility and epithelial ion transport within the colon. These processes are closely regulated by enteric serotonergic signaling. 5-Hydroxytryptamine (5-HT) plays a central role in enteric neuron activation, smooth muscle excitation, and epithelial secretory responses. Sustained hyperglycemia alters 5-HT receptor expression, serotonin transporter function, and enteric neuronal integrity. This review synthesizes current scientific advancements and discusses translational implications for targeted therapeutic development.