salicylates and Prediabetic-State

Topics: Humans; Insulin Resistance; Lipids; Obesity; Overweight; Prediabetic State; Salicylates

Docosahexaenoic acid (DHA 22:6n-3) and salicylate are both known to exert anti-inflammatory effects. This study investigated the effects of a novel bifunctional drug compound consisting of DHA and salicylate linked together by a small molecule that is stable in plasma but hydrolyzed in the cytoplasm. The components of the bifunctional compound acted synergistically to reduce inflammation mediated via nuclear factor κB in cultured macrophages. Notably, oral administration of the bifunctional compound acted in two distinct ways to mitigate hyperglycemia in high-fat diet-induced insulin resistance. In mice with diet-induced obesity, the compound lowered blood glucose by reducing hepatic insulin resistance. It also had an immediate glucose-lowering effect that was secondary to enhanced glucagon-like peptide-1 (GLP-1) secretion and abrogated by the administration of exendin(9-39), a GLP-1 receptor antagonist. These results suggest that the bifunctional compound could be an effective treatment for individuals with type 2 diabetes and insulin resistance. This strategy could also be employed in other disease conditions characterized by chronic inflammation.

Topics: Administration, Oral; Animals; Anti-Inflammatory Agents, Non-Steroidal; Blood Glucose; Cell Line, Transformed; Cell Line, Tumor; Cells, Cultured; Diet, High-Fat; Docosahexaenoic Acids; Glucagon-Like Peptide 1; Humans; Hypoglycemic Agents; Insulin Resistance; Liver; Macrophages; Mice, Inbred C57BL; Obesity; Prediabetic State; Prodrugs; Salicylates; Signal Transduction

Topics: Adolescent; Adult; Aged; Anti-Inflammatory Agents, Non-Steroidal; Cytokines; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Female; Glycated Hemoglobin; Humans; Male; Middle Aged; Prediabetic State; Psychiatric Status Rating Scales; Salicylates; Schizophrenia; Triglycerides; Young Adult

Topics: Acetone; Biguanides; Diabetes Complications; Diabetes Mellitus; Diabetic Ketoacidosis; Diet Therapy; Glucose Tolerance Test; Glycosuria; Holidays; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Secretion; Interpersonal Relations; Prediabetic State; Salicylates; Sports; Travel

Topics: Aminosalicylic Acids; Animals; Anti-Inflammatory Agents; Cinnamates; Flufenamic Acid; Gibberellins; Glycolates; Hypoglycemia; Male; ortho-Aminobenzoates; Phenylacetates; Prediabetic State; Rabbits; Salicylates