Prevention of insulin aggregation by dicarboxylic amino acids during prolonged infusion.
The dicarboxylic amino acids, aspartic and glutamic acid, at their isoelectric pH, reduced aggregation of insulin solutions in vitro for 16 days during continuous agitation at 37 degrees C. Unprotected insulin solutions, when infused via a 14-day implantable infusion device in diabetic Chinese hamsters, controlled plasma glucose levels for only 2 days, followed by escape coincident with insulin aggregation. However, when insulin solutions were protected with glutamic acid, euglycemia was maintained for the 14-day life of the device.
D000818:Animals; D001187:Artificial Organs; D001224:Aspartic Acid / Q000008:administration & dosage*; D006224:Cricetinae; D003412:Cricetulus; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy*; D004343:Drug Implants; D005260:Female; D005971:Glutamates / Q000008:administration & dosage*; D018698:Glutamic Acid; D007328:Insulin / Q000008:administration & dosage*; D007515:Islets of Langerhans / Q000378:metabolism*; D046911:Macromolecular Substances; D008297:Male
D004343:Drug Implants; D005971:Glutamates; D007328:Insulin; D046911:Macromolecular Substances; D001224:Aspartic Acid; D018698:Glutamic Acid