Possible mechanisms involved in improved beta cell function in pregnant women with type 1 diabetes
HELIYON
Authors: Nalla, Amarnadh; Ringholm, Lene; Sorensen, Susanne Norskov; Damm, Peter; Mathiesen, Elisabeth Reinhardt; Nielsen, Jens Hoiriis
Abstract
Pregnancy is known to be associated with an increased demand for insulin that is normally compensated by an increased beta cell mass and insulin secretion. Recent studies have suggested enhanced beta cell function during pregnancy in women with type 1 diabetes (T1D). To explore the possible mechanisms behind enhanced beta cell function during pregnancy in women with T1D we investigated the impact of circulating factors in serum from nine women from each group of pregnant women with and without T1D, after pregnancy and non-diabetic nonpregnant women on rat islet cell proliferation and apoptosis, and on T-lymphocyte activation. In addition, circulating levels of pancreatic hormones and selected cytokines and adipokines were measured. Rat islet cell proliferation was higher in serum from pregnant women with T1D (p < 0.05) compared to T1D women after pregnancy. Apoptosis in INS-1E cell was lower (p < 0.05) in serum from pregnant women with T1D compared to T1D women after pregnancy. T-lymphocyte cell (Jurkat) proliferation was reduced by serum from pregnant women without T1D only (p < 0.05). Higher C-peptide levels and lower levels of ghrelin, IL-6, MCP-1, IL-8 and adipsin were observed in pregnant women with T1D compared to T1D women after pregnancy. In conclusion, the improved beta cell function in women with T1D during pregnancy may be due to lower levels of proinflammatory cytokines and/or higher levels of pregnancy-associated growth factors.
(+)-Sesamin-oxidising CYP92B14 shapes specialised lignan metabolism in sesame
PLANT JOURNAL
Authors: Harada, Erisa; Murata, Jun; Ono, Eiichiro; Toyonaga, Hiromi; Shiraishi, Akira; Hideshima, Kosuke; Yamamoto, Masayuki P.; Horikawa, Manabu
Abstract
Sesamumspp. (sesame) are known to accumulate a variety of lignans in a lineage-specific manner. In cultivated sesame (Sesamum indicum), (+)-sesamin, (+)-sesamolin and (+)-sesaminol triglucoside are the three major lignans found richly in the seeds. A recent study demonstrated that SiCYP92B14 is a pivotal enzyme that allocates the substrate (+)-sesamin to two products, (+)-sesamolin and (+)-sesaminol, through multiple reaction schemes including oxidative rearrangement of alpha-oxy-substituted aryl groups (ORA). In contrast, it remains unclear whether (+)-sesamin in wild sesame undergoes oxidation reactions as inS. indicumand how, if at all, the ratio of the co-products is tailored at the molecular level. Here, we functionally characterised SrCYP92B14 as a SiCYP92B14 orthologue from a wild sesame,Sesamum radiatum, in which we revealed accumulation of the (+)-sesaminol derivatives (+)-sesangolin and its novel structural isomer (+)-7 '-episesantalin. Intriguingly, SrCYP92B14 predominantly produced (+)-sesaminol either through ORA or direct oxidation on the aromatic ring, while a relatively low but detectable level of (+)-sesamolin was produced. Amino acid substitution analysis suggested that residues in the putative distal helix and the neighbouring heme propionate of CYP92B14 affect the ratios of its co-products. These data collectively show that the bimodal oxidation mechanism of (+)-sesamin might be widespread acrossSesamumspp., and that CYP92B14 is likely to be a key enzyme in shaping the ratio of (+)-sesaminol- and (+)-sesamolin-derived lignans from the biochemical and evolutionary perspectives.