Insulin receptor partial agonists
Insulin dimers and insulin analog dimers that act as partial agonists at the insulin receptor are disclosed.
1. An insulin dimer selected from the group consisting of:
wherein the disulfide linkages between the Cys 6 and Cys 11 residues of the A-chain polypeptide and the disulfide linkages between the Cys 7 and Cys 20 of the A-chain to the Cys 7 and Cys 19 of the B-chain polypeptide, respectively, are represented by the solid line therebetween; wherein the linking moieties are covalently linked to the epsilon amino acid of the shown lysine residue wherein the A-chain polypeptide for Dimers 1-32, 35-62, 64-66, 69-79 and 82-86 has the amino acid sequence shown in SEQ ID NO: 1; and the B-chain polypeptide for Dimers 1-32, 35-62, 64-66, 69-79 and 82-86 has the amino acid sequence shown in SEQ ID NO: 2.
2. A composition comprising the insulin receptor partial agonist of claim 1 and a GLP-1 receptor agonist.
3. A method for treating diabetes comprising administering to an individual with diabetes a therapeutically effective amount of a composition comprising the insulin receptor partial agonist of claim 1 .
4. The method of claim 3 , wherein the diabetes is Type 1 diabetes, Type 2 diabetes, or gestational diabetes.
5. A composition for the treatment of diabetes comprising the insulin receptor partial agonist of claim 1 .
6. The composition of claim 5 , wherein the diabetes is Type 1 diabetes, Type 2 diabetes, or gestational diabetes.