Thiamine deficiency and protein secretion by pancreatic slices in vitro

Prasannan, K. G.; Sundaresan, R; Venkatesan, K

doi:10.1007/bf02124046

Cited by 20 publications

(17 citation statements)

References 9 publications

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“…The pancreas maintains a high level of thiamin (15), and deficiency of this vitamin negatively affects its exocrine and endocrine functions (16,17,21). As with all other mammalian cells, PAC cannot synthesize thiamin and must obtain the vitamin from circulation via transport across cell membranes.…”

mentioning

confidence: 99%

Mechanisms involved in the inhibitory effect of chronic alcohol exposure on pancreatic acinar thiamin uptake

Srinivasan

Subramanian

Said³

2014

American Journal of Physiology-Gastrointestinal and Liver Physi

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Srinivasan P, Subramanian VS, Said HM. Mechanisms involved in the inhibitory effect of chronic alcohol exposure on pancreatic acinar thiamin uptake. Am J Physiol Gastrointest Liver Physiol 306: G631-G639, 2014. First published February 13, 2014 doi:10.1152/ajpgi.00420.2013.-Pancreatic acinar cells (PAC) obtain thiamin from the circulation via a carrier-mediated process that involves thiamin transporters 1 and 2 (THTR-1 and THTR-2; products of SLC19A2 and SLC19A3, respectively). Chronic alcohol exposure of PAC inhibits thiamin uptake, and, on the basis of in vitro studies, this inhibition appears to be transcriptionally mediated. The aim of this study was to confirm the involvement of a transcriptional mechanism in mediating the chronic alcohol effect in in vivo settings and to delineate the molecular mechanisms involved. Using transgenic mice carrying full-length SLC19A2 and SLC19A3 promoters, we found that chronic alcohol feeding led to a significant reduction in the activity of SLC19A2 and SLC19A3 promoters (as well as in thiamin uptake and expression of THTR-1 and -2). Similar findings were seen in 266-6 cells chronically exposed to alcohol in vitro. In the latter studies, the alcohol inhibitory effect was found to be mediated via the minimal SLC19A2 and SLC19A3 promoters and involved the cis-regulatory elements stimulating protein 1 (SP1)/gut-enriched Kruppel-like factor and SP1-GG-box and SP1/GC, respectively. Chronic alcohol exposure of PAC also led to a significant reduction in the expression of the SP1 transcription factor, which upon correction (via expression) led to the prevention of alcohol inhibitory effects on not only the activity of SLC19A2 and SLC19A3 promoters but also on the expression of THTR-1 and -2 mRNA and thiamin uptake. These results demonstrate that the inhibitory effect of chronic alcohol exposure on physiological/ molecular parameters of thiamin uptake by PAC is mediated via specific cis-regulatory elements in SLC19A2 and SLC19A3 minimal promoters. SLC19A2; SLC19A3; alcohol feeding; thiamin transport; cis-regulatory elements THIAMIN (VITAMIN B1) IS ESSENTIAL for normal metabolic reactions and the health of all cell types, including pancreatic acinar cells (PAC). The vitamin acts as a cofactor for multiple enzymes (transketolase, pyruvate dehydrogenase, ␣-ketoglutarate dehydrogenase, and branched-chain ketoacid dehydrogenase); these enzymes participate in a variety of metabolic reactions related to oxidative energy (sugar) metabolism, ATP production (1, 26), and reduction of cellular oxidative stress (3,14). Thus it is not surprising that cellular thiamin deficiency leads to acute energy failure and to a propensity for oxidative stress (2,3,5,14,26); such a deficiency also leads to functional and structural abnormalities in mitochondria (2).The pancreas is a complex organ with important exocrine and endocrine functions. A variety of disease conditions and factors affect the health of this vital organ, leading to significant morbidity and mortality. The pancreas maintains a high level...

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confidence: 99%

Mechanisms involved in the inhibitory effect of chronic alcohol exposure on pancreatic acinar thiamin uptake

Srinivasan

Subramanian

Said³

2014

American Journal of Physiology-Gastrointestinal and Liver Physi

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“…1F)in the bone marrow of the proband and his late brother investigated in the current study. Previous studies reported that thiamine deficiency altered the secretion of pancreatic cells [17]. Rathanaswami et al [18].…”

Section: Discussionmentioning

confidence: 99%

A Novel Mutation of SLC19A2 in a Chinese Zhuang Ethnic Family with Thiamine-Responsive Megaloblastic Anemia

Xian

Liao

Shu

et al. 2018

Cell Physiol Biochem

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Background/Aims: Thiamine-responsive megaloblastic anemia syndrome is a rare autosomal recessive disorder resulting from mutations in SLC19A2, and is mainly characterized by megaloblastic anemia, diabetes, and progressive sensorineural hearing loss. Methods: We study a Chinese Zhuang ethnicity family with thiamine-responsive megaloblastic anemia. The proband of the study presented with anemia and diabetes, similar to his late brother, as well as visual impairment. All clinical manifestations were corrected with thiamine (30 mg/d) supplementation for 1–3 months, except for visual impairment, which was irreversible. The presence of mutations in all exons and the flanking sequences of the SLC19A2 gene were analyzed in this family based on the proband’s and his brother’s clinical data. Computer analysis and prediction of the protein conformation of mutant THTR-1. The relative concentration of thiamine pyrophosphate in the proband’s whole blood before and after initiation of thiamine supplement was measured by high performance liquid chromatography (HPLC). Results: Gene sequencing showed a homozygous mutation in exon 6 of the SLC19A2 gene (c.1409insT) in the proband. His parents and sister were diagnosed as heterozygous carriers of the c.1409insT mutation. Computer simulation showed that the mutations caused a change in protein conformation. HPLC results suggested that the relative concentration of thiamine pyrophosphate in the proband’s whole blood after thiamine supplement was significantly different (P=0.016) from that at baseline. Conclusions: This novel homozygous mutation (c.1409insT) caused the onset of thiamine-responsive megaloblastic anemia in the proband.

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“…The vitamin, in its pyrophosphate forms [mainly thiamine pyrophosphate (TPP), the most abundant form of thiamine in mammalian cells], is indispensable for oxidative energy (sugar) metabolism, ATP production in the mitochondria, and reduction of cellular oxidative stress (17,83); it is also important for maintaining normal mitochondrial structure and function (the mitochondrion is the major site of accumulation and utilization of thiamine) (13). Thus, low intracellular levels of thiamine lead to acute energy failure, propensity for oxidative stress, and mitochondrial abnormalities (13,17,64,83,101). There are two types of thiamine deficiencies: systemic and localized (tissue-specific).…”

Section: Production Of Wsv By Intestinal Microbiota and Their Absorptmentioning

confidence: 99%

Recent advances in transport of water-soluble vitamins in organs of the digestive system: a focus on the colon and the pancreas

Said

2013

American Journal of Physiology-Gastrointestinal and Liver Physi

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This review focuses on recent advances in our understanding of the mechanisms and regulation of water-soluble vitamin (WSV) transport in the large intestine and pancreas, two important organs of the digestive system that have only recently received their fair share of attention. WSV, a group of structurally unrelated compounds, are essential for normal cell function and development and, thus, for overall health and survival of the organism. Humans cannot synthesize WSV endogenously; rather, WSV are obtained from exogenous sources via intestinal absorption. The intestine is exposed to two sources of WSV: a dietary source and a bacterial source (i.e., WSV generated by the large intestinal microbiota). Contribution of the latter source to human nutrition/health has been a subject of debate and doubt, mostly based on the absence of specialized systems for efficient uptake of WSV in the large intestine. However, recent studies utilizing a variety of human and animal colon preparations clearly demonstrate that such systems do exist in the large intestine. This has provided strong support for the idea that the microbiota-generated WSV are of nutritional value to the host, and especially to the nutritional needs of the local colonocytes and their health. In the pancreas, WSV are essential for normal metabolic activities of all its cell types and for its exocrine and endocrine functions. Significant progress has also been made in understanding the mechanisms involved in the uptake of WSV and the effect of chronic alcohol exposure on the uptake processes.

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Thiamine deficiency and protein secretion by pancreatic slices in vitro

Cited by 20 publications

References 9 publications

Mechanisms involved in the inhibitory effect of chronic alcohol exposure on pancreatic acinar thiamin uptake

Mechanisms involved in the inhibitory effect of chronic alcohol exposure on pancreatic acinar thiamin uptake

A Novel Mutation of SLC19A2 in a Chinese Zhuang Ethnic Family with Thiamine-Responsive Megaloblastic Anemia

Recent advances in transport of water-soluble vitamins in organs of the digestive system: a focus on the colon and the pancreas

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