Among glucose-recognizing paraneurons, the gustatory cell is believed to have a glucoreceptor, while the pancreatic B cell is thought to metabolize glucose for signal production for insulin release. To investigate whether a common mechanism of glucose recognition exists among these cells, we have studied the interaction of the anomers of glucose or its derivative, known as a sugar taste inhibitor, with the pancreatic B cell of normal and diabetic rats. Inhibitors of the sugar taste response inhibited glucose-induced insulin release in various manners. A non-specific inhibitor, dibucaine, impaired not only the insulin response to glucose but also the ability to discriminate the anomers of glucose, without inhibiting glucose oxidation in the islets. Dibucaine also inhibited insulin release induced by a non-glucose secretagogue, tolbutamide. The alpha anomer, but not the beta anomer, of p-nitrophenyl-D-glucopyranoside, a specific-competitive inhibitor of sugar taste response, inhibited glucose-induced insulin release, but did not inhibit insulin release induced by non-glucose secretagogues or glucose oxidation. The pancreatic B cell of a non-insulin-dependent diabetes (NIDD) rat model, the NSZ rat, exhibited low insulin response to glucose and did not discriminate between the two anomers of glucose. The diabetic B cell responded to non-glucose secretagogues to the same extent as the control. Glucose oxidation in the diabetic islets was not impaired. These findings, together with previous ones, suggest that the gustatory and pancreatic B cells have a common glucose recognition site, which has a steric preference for the alpha anomer and is impaired in NIDD.