Sandbox Reserved 1167: Difference between revisions

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== Clinical Relevance ==

Because of GCGR's role in glucose homeostasis, GCGRis a potential drug target for [https://en.wikipedia.org/wiki/Diabetes_mellitus_type_2 Type 2 diabetes]. Specifically, molecules that antagonize the glucagon receptor may be able to lower blood sugar levels. Among experimental treatments, two antibodies, mAb1 and mAb23, target the ECD domain of the GCGR interrupting glucagon binding<ref name="other_article'>PMID:22908259</ref>. While the entire cleft of the ECD is blocked by mAb1, mAb3 blocks glucagon binding by stabilizing a conformation of the ECD that promotes receptor inactivation <ref name="other_article'>PMID:22908259</ref>. Another antibody, mAb7, inhibits GCGR allosterically<ref>PMID:24189067</ref>. Through binding to a site outside of the binding pocket, mAb7 inhibits the receptor without interacting with essential glucagon binding residues. Disrupting the normal interactions between the ECD and the 7tm domains, these antibodies inhibit the receptor's function and help to lower blood glucose level.

Because of GCGR's role in glucose homeostasis, GCGRis a potential drug target for [https://en.wikipedia.org/wiki/Diabetes_mellitus_type_2 Type 2 diabetes]. Specifically, molecules that antagonize the glucagon receptor may be able to lower blood sugar levels. Among experimental treatments, two antibodies, mAb1 and mAb23, target the ECD domain of the GCGR interrupting glucagon binding<ref name='other_article'>PMID:22908259</ref>. While the entire cleft of the ECD is blocked by mAb1, mAb3 blocks glucagon binding by stabilizing a conformation of the ECD that promotes receptor inactivation <ref name='other_article'>PMID:22908259</ref>. Another antibody, mAb7, inhibits GCGR allosterically<ref>PMID:24189067</ref>. Through binding to a site outside of the binding pocket, mAb7 inhibits the receptor without interacting with essential glucagon binding residues. Disrupting the normal interactions between the ECD and the 7tm domains, these antibodies inhibit the receptor's function and help to lower blood glucose level.

As GCGR holds great promise as a therapeutic target, there are currently three drugs under development that are designed to treat Type 2 Diabetes by targeting the human glucagon receptor<ref name='therapeutic_article'>DOI 10.1016/j.tips.2013.11.001</ref>. Although they are still in phase I of their clinical trials, preliminary research has shown promising results<ref>DOI 10.2174/1573399810666141224121927</ref>.

Sandbox Reserved 1167: Difference between revisions

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 == Clinical Relevance ==
-Because of GCGR's role in glucose homeostasis, GCGRis a potential drug target for [https://en.wikipedia.org/wiki/Diabetes_mellitus_type_2 Type 2 diabetes]. Specifically, molecules that antagonize the glucagon receptor may be able to lower blood sugar levels. Among experimental treatments, two antibodies, mAb1 and mAb23, target the ECD domain of the GCGR interrupting glucagon binding<ref name="other_article'>PMID:22908259</ref>. While the entire cleft of the ECD is blocked by mAb1, mAb3 blocks glucagon binding by stabilizing a conformation of the ECD that promotes receptor inactivation <ref name="other_article'>PMID:22908259</ref>. Another antibody, mAb7, inhibits GCGR allosterically<ref>PMID:24189067</ref>. Through binding to a site outside of the binding pocket, mAb7 inhibits the receptor without interacting with essential glucagon binding residues. Disrupting the normal interactions between the ECD and the 7tm domains, these antibodies inhibit the receptor's function and help to lower blood glucose level.
+Because of GCGR's role in glucose homeostasis, GCGRis a potential drug target for [https://en.wikipedia.org/wiki/Diabetes_mellitus_type_2 Type 2 diabetes]. Specifically, molecules that antagonize the glucagon receptor may be able to lower blood sugar levels. Among experimental treatments, two antibodies, mAb1 and mAb23, target the ECD domain of the GCGR interrupting glucagon binding<ref name='other_article'>PMID:22908259</ref>. While the entire cleft of the ECD is blocked by mAb1, mAb3 blocks glucagon binding by stabilizing a conformation of the ECD that promotes receptor inactivation <ref name='other_article'>PMID:22908259</ref>. Another antibody, mAb7, inhibits GCGR allosterically<ref>PMID:24189067</ref>. Through binding to a site outside of the binding pocket, mAb7 inhibits the receptor without interacting with essential glucagon binding residues. Disrupting the normal interactions between the ECD and the 7tm domains, these antibodies inhibit the receptor's function and help to lower blood glucose level.
 As GCGR holds great promise as a therapeutic target, there are currently three drugs under development that are designed to treat Type 2 Diabetes by targeting the human glucagon receptor<ref name='therapeutic_article'>DOI 10.1016/j.tips.2013.11.001</ref>. Although they are still in phase I of their clinical trials, preliminary research has shown promising results<ref>DOI 10.2174/1573399810666141224121927</ref>.