Current methods for measuring long-term glycemia in patients with diabetes are HbA 1c and advanced glycation end products (AGEs), which are estimated by phenyl boronate affinity chromatography and competitive enzyme-linked immunosorbent assay, respectively. In this study, we hypothesize that the intrinsic fluorescence property of hemoglobin-AGE (Hb-AGE) may be a simple, accurate, and therefore better index for longterm glycemic status due to its highly specific nature and longer half-life. To establish this contention, in vitro and in vivo experiments were carried out. The former was performed by incubating commercially available hemoglobin with 5 and 20 mmol/l glucose and the latter through experimentally induced (streptozotocin) diabetes in an animal model (male Wistar rats) to identify the new fluorophore formed due to the nonenzymatic glycosylation of hemoglobin. An adduct exhibiting fluorescence at 308/345 nm of excitation/emission wavelengths has been identified and its time-dependent formation established. Under in vitro conditions, the first appearance of the new fluorophore was noticed only after a period of 2 months, whereas under in vivo conditions, it increased significantly after 2 months of hyperglycemia. Consistent with the observations, studies on patients with type 2 diabetes demonstrated an elevated level of this new fluorescent adduct in patients with persisting high levels of plasma glucose for >2 months. Based on the results obtained, Hb-AGE appears to be an efficient fluorescence-based biosensing molecule for the long-term monitoring of glycemic control in diabetes.
1. Abdominal colic and constipation are symptoms of lead poisoning in man, but mechanisms of these effects are not yet fully understood. In this study the effect of lead acetate on contractility of rat duodenum was determined in vivo in 70 rats. 2. Rats were orally dosed with 44 mg/kg per day lead as 53 mmol/L lead acetate, for 4 weeks. Motility of the duodenum was recorded with an electrical impedance probe. 3. A significant decrease in the amplitude of contraction waves in case of treated rats was observed compared with controls which received an equal volume of saline. The number of contractions increased from 26 per min in controls to 33 per min in treated rats. Gastrointestinal transit rate decreased by 64% and 69% after 9 and 15 days of lead exposure, respectively.
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