A single-chain insulin analogue comprises a B-chain insulin polypeptide sequence connected to an A-chain insulin polypeptide sequence by a C-domain polypeptide sequence. The B-chain insulin polypeptide sequence contains a Cysteine substitution at position B4. The A-chain insulin polypeptide sequence contains a Cysteine substitution at position A10. The C-domain polypeptide sequence is 4 to 11 amino acids long. The analogue mitigates the unfavorable activity of this 4thdisulfide bridge in conventional two-chain insulin analogues resulting in a duration of insulin signaling similar to that of wild-type insulin. A method of treating a patient with diabetes mellitus comprises the administration of a physiologically effective amount of the protein or a physiologically acceptable salt thereof to a patient. Use of a single-chain insulin analogue of the present invention in an insulin delivery device (such as a pump or pen) or as part of a high-temperature polymer-melt manufacturing process.單鏈胰島素類似物包含藉由C結構域多肽序列連接至A鏈胰島素多肽序列之B鏈胰島素多肽序列。該B鏈胰島素多肽序列在B4位置含有半胱胺酸取代。該A鏈胰島素多肽序列在A10位置含有半胱胺酸取代。該C結構域多肽序列長度為4至11個胺基酸。該類似物減輕此第4雙硫鍵在習用雙鏈胰島素類似物中之不利活性，從而產生類似於野生型胰島素之胰島素信號傳導之持續時間。治療糖尿病患者之方法包含向患者投與生理有效量之蛋白質或其生理上可接受之鹽。本發明係關於本發明單鏈胰島素類似物之用途，其用於胰島素遞送器件(例如幫浦或筆)中或用作高溫聚合物-熔體製造方法之一部分。
