PHAR 430 Lecture 13: 13. Diabetes - Melina
Document Summary
The use of these compounds can be traced back to medieval times - the plant galega officinalis was used to 1) promote perspiration during plague epidemics; 2) stimulate lactation in cows and 3) relieve intense urination associated with diabetes. Plant contains compounds like galegine with hypoglycemic properties, but duration of action was deemed too short. Some of the guanidines proved too toxic for use. Despite toxicities associated with guanidine, the biguanides were shown to exert beneficial effects & quickly became available therapeutic agents for diabetes in the 1950s. Improve glycemic control by inhibiting gluconeogenesis in the liver, incr glycolysis, reducing glucose oxidation, decr intestinal glucose absorption, contributing to the translocation of glucose transporters to the cell surface for insulin-independent glucose uptake. Metformin is a first line treatment for t2d as a monotherapy or in combo with sulfonylureas or. Incr ampk (master regulator of metabolism) activity in the liver decr ldl synthesis.
