True statement regarding mechanism of action of sulfonylureas is: March 2008, September 2010
Ans. C Act on SURI receptors on pancreatic beta cell membrane Sulfonylureas (Tolbutamide/ chlorpropamide/Glibenclamide) bind strongly to plasma proteins. Sulfonylureas are only useful in Type II diabetes, as they act on SURI receptors on pancreatic beta cell membrane, stimulating endogenous release of insulin. They work best with patients over 40 years old, who have had diabetes mellitus for under ten years. They cannot be used with type I diabetes, or diabetes of pregnancy. They can be safely used with metformin or -glitazones. The primary side effect is hypoglycemia. Meglitinides (Repaglinide/ nateglinide) help the pancreas produce insulin and are often called "sho-acting secretagogues." They act on the same potassium channels as sulfonylureas, but at a different binding site. By closing the potassium channels of the pancreatic beta cells, they open the calcium channels, hence enhancing insulin secretion Biguanides (Metformin) reduce hepatic glucose output and increase uptake of glucose by the periphery, including skeletal muscle. Although it must be used with caution in patients with impaired liver or kidney function, metformin, a biguanide, has become the most commonly used agent for type 2 diabetes in children and teenagers. Amongst common diabetic drugs, metformin is the only widely used oral drug that does not cause weight gain Thiazolidinediones (TZDs) (rosiglitazone) bind to PPARd, a type of nuclear regulatory protein involved in transcription of genes regulating glucose and fat metabolism. These PPARs act on Peroxysome Proliferator Responsive Elements (PPRE). The PPREs influence insulin sensitive genes, which enhance production of mRNAs of insulin dependent enzymes. The final result is better use of glucose by the cells.
Increased peripheral utilization of glucose
Reduce hepatic glucose output
Act on SURI receptors on pancreatic beta cell membrane
Transcription of genes regulating glucose metabolism