Aminoguanidine exerts a beta-cell function-preserving effect in high glucose-cultured beta-cells (INS-1).
We investigated the effects of aminoguanidine (AG) on beta-cell functions in an insulin secreting cell line (INS-1). Culture with 27mM glucose for one week markedly decreased both insulin release and insulin content compared to culture in 0.8 mM or 3.3 mM glucose. Relative to culture at 27 mM glucose alone, the co-exposure to 1 mM AG almost doubled basal as well as glucose or 25 mM KCl-stimulated insulin release and increased insulin content by 42%. AG failed to affect release and content in cells cultured at 0.8 or 3.3 mM glucose. Preproinsulin mRNA content in 27mM glucose-cultured cells was 52% suppressed compared to 0.8mM glucose-cultured cells, and AG treatment partially counteracted this decline. Advanced glycosylation end product (AGE)-associated fluorescence (370nm excitation and 440 nm emission) of cells' extracts did not differ between 27mM and 0.8mM glucose-cultured cells after 1 week of culture and fluorescence was unaffected by AG. Accumulation of nitrite into culture media was markedly increased from 27mM glucose-cultured cells, and this accumulation was 33% suppressed by AG. In conclusion, AG partially protects against glucotoxic effects in INS-1 cells. These beneficial effects may involve a decrease in early glycation products and/or nitric oxide synthase (NOS) activity. The effects which were obtained after one week of high glucose exposure may supplement AGE-associated effects seen after chronically elevated glucose.
Tajiri
Y
Y
Department of Molecular Medicine, Karolinska Hospital, Karolinska Institute, Stockholm, Sweden.
Grill
V
V
D000818:Animals; D002460:Cell Line; D005786:Gene Expression Regulation / Q000187:drug effects; D005947:Glucose / Q000494:pharmacology*; D017127:Glycation End Products, Advanced / Q000032:analysis; D006146:Guanidines / Q000494:pharmacology*; D007328:Insulin / Q000235:genetics* / Q000378:metabolism; D000078790:Insulin Secretion; D007340:Insulinoma; D007515:Islets of Langerhans / Q000187:drug effects* / Q000502:physiology; D007700:Kinetics; D009573:Nitrites / Q000378:metabolism; D010190:Pancreatic Neoplasms; D011189:Potassium Chloride / Q000494:pharmacology; D011384:Proinsulin / Q000235:genetics*; D011498:Protein Precursors / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D013050:Spectrometry, Fluorescence; D013997:Time Factors; D014158:Transcription, Genetic / Q000187:drug effects
D017127:Glycation End Products, Advanced; D006146:Guanidines; D007328:Insulin; D009573:Nitrites; D011498:Protein Precursors; D012333:RNA, Messenger; C013737:preproinsulin; D011189:Potassium Chloride; D011384:Proinsulin; D005947:Glucose; C004479:pimagedine