Insulin Structure & Function

spinqualitylabelsall models Human insulin chain A (grey) and chain B (green), 2hiu Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Function Insulin is made by the pancreatic islet beta cells in response to elevated blood glucose levels. Insulin signals cells that the body is in the "fed" state, and that it should take up glucose from the blood and make other appropriate response. For example, in the liver glycogen synthesis is turned on, which provides a supply of glucose when the blood glucose levels fall under fasting conditions. Insulin also increases fat synthesis in adipocytes. In type 1 diabetes, the pancreatic cells do not release insulin, resulting in high blood sugar levels and increased fat metabolism. Consequently, there is "spillover" of glucose into the urine, and weight loss due to the loss of body fat stores. Structure Insulin is composed of two different types of peptide chains. Chain A has 21 amino acids and Chain B has 30 amino acids. Both chains contain alpha helices but no beta strands. There are 3 conserved disulfide bridges which help keep the two chains together. Insulin can also form dimers in solution due to the hydrogen bonding between the B chains (shown as white lines). The dimers can further interact to form hexamers due to interaction between hydrophobic surfaces. This scene highlights the hydrophobic (gray) and polar (purple) parts of an insulin monomer at a pH of 7. A number of insulin variants have been made to favor either the monomeric or hexameric form. Deletion of the five C terminal residues of the B chain creates a monomer only form. This portion of the B chain is involved in hydrogen bonds between the B chain of one monomer and the A (marked C) and B (marked D) chain of another monomer; without this region, the hexamers do not form. Lispro is another fast acting insulin; it has the lysine and proline at the end of the B subunit swapped. This allows the lysine to make a hydrogen bond with tyrosine 26, which also favors formation of the active monomer state.

3D structures of insulin

Insulin

Additional Resources

Thanks to 'User:Whitney_Stoppel' for the hexameric insulin scenes. For additional information, see: Diabetes & Hypoglycemia

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Ann Taylor, Pat McQuaid, David Canner, Michal Harel