Truman B. Grayson's research while affiliated with University of Alabama at Birmingham and other places

... These sites are located at or near CpG islands and other regulatory regions (Table 1). Thus, variations in their methylation may be linked to altered expression of genes that contribute to lipid metabolism, hyperglycemia, and inflammation (Jones et al., 2021;Lu et al., 2022). While studies are limited, MR for methylation and cardiometabolic traits suggest that altered methylation is the consequence, not the cause, of metabolic dysfunction (Dekkers et al., 2016;Sayols-Baixeras et al., 2018;Zaghlool et al., 2018). ...

... Similarly, we found an increase in the level of GDF15 prior to T1D onset. There is also an increase of GDF15 expression in β cells under endoplasmic reticulum stress conditions [47]. However, the level of GDF15 in pancreatic islets is reduced in NOD mice with insulitis and depleted in humans with T1D [13]. ...

... Verapamil treatment slowed the progression of diabetes, improved pancreatic beta-cell function and thus contributed to decreasing insulin requirements for 2 years. The beneficial effect of verapamil disappeared when the treatment was stopped [7]. In 2023, Gregory P Forlenza from the United States and his research group emphasized the experimental evidence suggesting that the over-expression of thioredoxin-interacting protein leads apoptosis and death of beta cell in the pancreas. ...

... QotM #4 focused on a search for the molecular target of a novel small molecule that has demonstrated efficacy in murine models of diabetes, with an added benefit of improving fatty liver [23]. The specific question was: "What is the molecular target of an anti-diabetic small molecule?" ...

... Serum miRNA-204 was increased in children with T1D, but not in those with type-2 diabetes, and was inversely correlated with cell functioning. Therefore, it could serve as a novel biomarker for T1D-associated β-cell damage (35). ...

... The last two modifications are considered irreversible [86,87]. The formation of sulfenic acid is recorded in proteins involved in the regulation of apoptosis, activation, and proliferation of immune cells [89][90][91]. Sulfene groups have also been identified in the catalytic sites of some enzymes, including peroxiredoxins (Prx), NADH peroxidase, and others [86,87,92]. It is known that cysteine residues in the molecules of some transcription factors (for example, NF-kB, Fos and Jun) and proteins involved in intracellular signaling and metabolism (for example, glyceraldehyde-3-phosphate dehydrogenase (GPDH), glutathione reductase (GR), proteine tyrosine phosphatase (PTP), kinases and proteases), can be oxidized to sulfene groups under conditions in vitro [87]. ...

... It is worth mentioning here that at this time other drugs that modulate insulin exocytosis to protect β-cells are upstream of SNARES. For example, Sulfonylureas (chlorpropamide, glipizide, etc.) increase insulin secretion via binding to ATP-dependent K + channel [1,194]; GLP-1 agonists (liraglutide, exenatide) boost insulin secretion via binding to GLIP-1 receptor in the β-cell [1,195]; and additionally, inhibitors of Thioredoxin-interacting protein (TXNIP), promote insulin production and GLP-1 signaling via regulation of microRNA, are emerging as a potential treatment option for diabetes [196,197]. However, since all of these abovementioned drugs work upstream of SNAREs, there may be effects beyond the distal steps of insulin exocytosis, again implying the significance of developing drugs for specific modulations of SNARE and SNARE regulatory proteins in the β-cell. ...

... Understanding the role of miR-204-5p is however more complex. While in 3 different studies overexpression in human islets showed increased apoptosis, reduced insulin secretion, and decreased expression of glucagon-like peptide 1 (GLP-1) receptors (25,31,32), a more recent human islet study neither validate the gene targets nor confirm the reduction in insulin secretion (33). Within the group of miRNAs differentially expressed in T2D islets and involved in the regulation of insulin secretion, we found increased expression of miR-187-3p, miR-124-3p, miR-463-3p, miR-130a-3p, miR-130b-3p, miR-152-3p, and miR-200c-3p (34-38) to be involved in β-cell dysfunction, while decreased expression of miR-7-5p (miR-7a; (39)) seems to be a mechanism by which this miRNA exerts a compensatory regulatory effect on exocytosis (Fig. 2). ...

... 24 It has been demonstrated that miR-204 activates the unfolded protein response signaling, promoting endoplasmic reticulum stress and apoptosis in b-cell lines and human islets. 52 ...

... In contrast, some gene groups were conversely expressed in NOD and db/db + mSTZ analyses. For example, NOD group T1-down3, containing some genes involved in adaptive stress response (Txnip and Herpud1) 33,111 , was, in addition to healthy cells, also highly expressed in db/db and mSTZ model cells. ...