Success of diabetic drugs – A short review


Recently, there have been many studies on diabetic drugs and the success of them.

The pancreatic beta cells of a specially bred zebrafish glow yellow to indicate the production of insulin. The pancreatic cells not responsible for producing insulin glow red. Credit: Johns Hopkins Medicine

In August last year, Johns Hopkins scientists reported success using zebrafish embryos to identify potential new diabetes drugs. In the study, more than 500,000 zebrafish embryos were analyzed. Eventually, the researchers identified 24 compounds that effectively increased beta cell number in these animals. Besides identifying new drug candidates, the research also identified biological pathways not previously known to have an effect on beta cell production. For example, some of the newly identified drugs appeared to increase beta cell production through a pathway involving serotonin, a chemical better known for transmitting signals in the brain.

Another interesting study published very recently, identified the target proteins for a class of diabetic drugs and the mechanism of action of these drugs on proteins. Weiping Han from the A*STAR Singapore Bioimaging Consortium, with researchers at Stanford University led a collaborative study to determine why drugs that stimulate postprandial insulin secretion in people with type 2 diabetes have varying efficacy.

Drugs containing metabolic hormones, such as glucagon-like peptide-1 (GLP-1), have proven effective at boosting insulin secretion and restoring glucose homeostasis in these patients.

Flowchart NEW

Han and his colleagues found that the membrane protein synaptotagmin-7 not only acts as a calcium sensor regulating insulin secretion in pancreatic beta cells, but they are the “key target”of GLP – 1 class of drugs.

Specifically, they found that in the presence of glucose and calcium, GLP-1 triggers the phosphorylation of synaptotagmin -7, which enhances insulin release. When glucose levels return to normal, no matter how we modify the protein, it won’t stimulate insulin secretion.

By identifying the interacting proteins, other functions of synaptotagmin protein such as neurotransmitter release from neurons during learning, memory and other higher-order brain activities could be explained.

More on this can be read here.