methimazole and Hyperglycemia

Topics: Autoantibodies; Autoimmune Diseases; Diagnosis, Differential; HLA Antigens; Humans; Hyperglycemia; Hyperinsulinism; Hypoglycemia; Insulin Antibodies; Methimazole; Syndrome; Tiopronin

Adenosine 5'-monophosphate activated protein kinase (AMPK) has emerged as a major potential target for novel antidiabetic drugs. We studied the structure of 2-chloro-5-((Z)-((E)-5-((5-(4,5-dimethyl-2-nitrophenyl)furan-2-yl)methylene)-4-oxothiazolidin-2-ylidene)amino)benzoic acid (PT-1), which attenuates the autoinhibition of the enzyme AMPK, for the design and synthesis of different benzothiazoles with potential antidiabetic activity. We synthesized several structurally related benzothiazole derivatives that increased the rate of glucose uptake in L6 myotubes in an AMPK-dependent manner. One compound, 2-(benzo[d]thiazol-2-ylmethylthio)-6-ethoxybenzo[d]thiazole (34), augmented the rate of glucose uptake up to 2.5-fold compared with vehicle-treated cells and up to 1.1-fold compared to PT-1. Concomitantly, it elevated the abundance of GLUT4 in the plasma membrane of the myotubes and activated AMPK. Subcutaneous administration of 34 to hyperglycemic Kuo Kondo rats carrying the Ay-yellow obese gene (KKAy) mice lowered blood glucose levels toward the normoglycemic range. In accord with its activity, compound 34 showed a high fit value to a pharmacophore model derived from the PT-1.

Topics: Adenosine Triphosphate; AMP-Activated Protein Kinases; Animals; Benzothiazoles; Blood Glucose; Cell Line; Cell Membrane; Enzyme Activation; Glucose; Glucose Transporter Type 4; Hyperglycemia; Hypoglycemic Agents; Male; Mice; Models, Chemical; Molecular Structure; Muscle Fibers, Skeletal; Rats

A 15-year-old female presented to a pediatric emergency department with glycosuria, ketonuria, and hyperglycemia and was admitted with a presumed diagnosis of diabetes mellitus. The patient required no insulin therapy and only minor dietary modification to maintain euglycemia. Clinical examination and laboratory findings revealed a primary diagnosis of Graves' hyperthyroidism with associated impaired glucose tolerance. Here, we review the mechanisms of thyrotoxicosis resulting in impaired glucose metabolism.

Topics: Adolescent; Adrenergic beta-Antagonists; Antithyroid Agents; Blood Glucose; Female; Graves Disease; Humans; Hyperglycemia; Iodine Radioisotopes; Methimazole; Propranolol; Thyrotoxicosis; Thyroxine

Topics: Adult; Diabetes Complications; Female; Humans; Hyperglycemia; Hyperthyroidism; Methimazole; Osmolar Concentration