Can aggregation of insulin govern its fate in the intestine? Implications for oral delivery of the drug.
The objective of this study is to elucidate the role of low-molecular weight biogenic agents, resembling dietary-derived products naturally occurring in the intestine, in the regulation of transformations of soluble aggregation-prone insulin into aggregates of higher order. In the course of model experiments, a striking potential of the amino acids L-arginine (Arg) and L-lysine (Lys) and a number of positively charged peptides to induce formation of heterogenic supramolecular structures of insulin was demonstrated under environment conditions where the protein aggregation in their absence was not observed. This phenomenon is assumed to be essential for elaboration of strategies of oral delivery of insulin to diabetic patients supplemented by controlling the pH values of the intestinal environment where the drug is released.
A.N. Bach Institute of Biochemistry, Russian Academy of Sciences, Leninsky Prospect, 33, Moscow 119071, Russia.
Ekaterina
E
Smirnova
A.N. Bach Institute of Biochemistry, Russian Academy of Sciences, Leninsky Prospect, 33, Moscow 119071, Russia.
Irina
I
Safenkova
A.N. Bach Institute of Biochemistry, Russian Academy of Sciences, Leninsky Prospect, 33, Moscow 119071, Russia.
Vita
V
Stein-Margolina
A.N. Bach Institute of Biochemistry, Russian Academy of Sciences, Leninsky Prospect, 33, Moscow 119071, Russia.
Vladimir
V
Shubin
A.N. Bach Institute of Biochemistry, Russian Academy of Sciences, Leninsky Prospect, 33, Moscow 119071, Russia. Electronic address: bella@inbi.ras.ru.
Bella
B
Gurvits
D000284:Administration, Oral; D001120:Arginine / Q000737:chemistry / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000737:chemistry* / Q000378:metabolism; D007328:Insulin / Q000008:administration & dosage / Q000737:chemistry* / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism*; D007700:Kinetics; D008239:Lysine / Q000737:chemistry / Q000378:metabolism; D008954:Models, Biological; D066329:Protein Aggregates; D011487:Protein Conformation; D055503:Protein Multimerization
D007004:Hypoglycemic Agents; D007328:Insulin; D066329:Protein Aggregates; D001120:Arginine; D008239:Lysine
Arginine; Human recombinant insulin; Oral delivery; Peptides; Protein aggregation; Supramolecular structures