Involvement of histamine and histamine H2 receptors in nicotinamide-induced differentiation of human amniotic epithelial cells into insulin-producing cells.
OBJECTIVE
Human amniotic epithelial cells (HAEC) resemble stem cells in their ability to differentiate into all three germ layers: endoderm, mesoderm, and ectoderm. Histamine receptors are expressed on HAEC. We examined the influence of histamine, and H(1) and H(2) antagonists on the generation of pancreatic islet beta-like cells from HAEC.


METHODS
HAEC were isolated after term pregnancies (N = 12) and cultured for 14 days with nicotinamide (10 mM) in normoxia. Altogether, 72 cultures were established. Histamine (100 microM) effects were investigated with mepyramine (10 microM) or cimetidine (10 microM). After 7 and 14 days, the mean concentration of C-peptide (MCCP) in the culture medium was measured immunoenzymatically as a marker of pancreatic differentiation.


RESULTS
MCCP was approximately threefold higher on day 14, compared to day 7. Histamine significantly increased MCCP, and more evident differences were observed after 7 days of culture than after 14 days. The mean percent increase +/-SEM in MCCP amounted to 142.19 +/- 21.7 and 79.03 +/- 12.35 compared to the controls on day 7 and 14, respectively. H(2) blockade significantly reduced histamine-related increase in MCCP, both on day 7 and 14 by 88.7 +/- 14.3 and 39.2 +/- 12.4%, respectively. H(1) receptor antagonist did not affect MCPP.


CONCLUSIONS
Nicotinamide-induced pancreatic differentiation of HAEC into beta-like cells may be augmented, probably at its earlier stage, by histamine acting via H(2) receptors.
Szukiewicz
D
D
Department of General and Experimental Pathology, Medical University of Warsaw, Warsaw, Poland. Dszukiewicz@hotmail.com
Szewczyk
G
G
Mittal
T K
TK
Rongies
W
W
Maslinski
S
S
D000328:Adult; D000653:Amniotic Fluid / Q000166:cytology*; D002096:C-Peptide / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects*; D002478:Cells, Cultured; D002927:Cimetidine / Q000494:pharmacology; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D006632:Histamine / Q000494:pharmacology / Q000502:physiology*; D006634:Histamine H1 Antagonists / Q000494:pharmacology; D006635:Histamine H2 Antagonists / Q000494:pharmacology; D006801:Humans; D007328:Insulin / Q000096:biosynthesis*; D050417:Insulin-Secreting Cells / Q000378:metabolism* / Q000502:physiology*; D009536:Niacinamide / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology*; D011247:Pregnancy; D011738:Pyrilamine / Q000494:pharmacology; D011970:Receptors, Histamine H2 / Q000187:drug effects* / Q000502:physiology*
D002096:C-Peptide; D006634:Histamine H1 Antagonists; D006635:Histamine H2 Antagonists; D007328:Insulin; D018722:Nicotinic Agonists; D011970:Receptors, Histamine H2; D009536:Niacinamide; D002927:Cimetidine; D006632:Histamine; D011738:Pyrilamine