Biotin increases glucokinase expression via soluble guanylate cyclase/protein kinase G, adenosine triphosphate production and autocrine action of insulin in pancreatic rat islets☆

Flores, Angélica; Tovar, Armando R.; Marín‐Hernández, Álvaro; Rojas-Ochoa, Alberto; Fernández-Mejía, Cristina

doi:10.1016/j.jnutbio.2009.03.009

Cited by 29 publications

(32 citation statements)

References 63 publications

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“…The vitamin plays a role in the expression of genes that are critical for maintaining the differentiated phenotype of pancreatic beta cells and in preserving their mass; it also plays a role in insulin secretion (3,30,39,44) and in expression of glucokinase (30,39) and Pdx1 (44), proteins that favor function and preservation of pancreatic beta cells (2,21). Despite the importance of biotin for the normal homeostasis and function of the endocrine pancreas, little is known about how cells of this important organ take up biotin, how the process is regulated, and how internal and external factors affect the uptake process.…”

Section: Discussionmentioning

confidence: 99%

“…In reference to the latter, the vitamin has been shown to increases the expression of pancreatic and duodenal homeobox 1 (Pdx-1) (44), a critical transcription factor for the expression of insulin, and several genes involved in its synthesis and secretion by pancreatic beta cells (2). In pancreatic beta cells, biotin appears to increase the expression of insulin receptor (7) and glucokinase (3,30,39), a rate-limiting enzyme in glucose-stimulated insulin secretion (20). It also decreases the expression of several gluconeogenic genes (6,36).…”

mentioning

confidence: 99%

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Biotin uptake by mouse and human pancreatic beta cells/islets: a regulated, lipopolysaccharide-sensitive carrier-mediated process

Ghosal

Sekar

Said

2014

American Journal of Physiology-Gastrointestinal and Liver Physi

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Ghosal A, Sekar TV, Said HM. Biotin uptake by mouse and human pancreatic beta cells/islets: a regulated, lipopolysaccharidesensitive carrier-mediated process. Am J Physiol Gastrointest Liver Physiol 307: G365-G373, 2014. First published June 5, 2014; doi:10.1152/ajpgi.00157.2014.-Biotin is essential for the normal function of pancreatic beta cells. These cells obtain biotin from their surroundings via transport across their cell membrane. Little is known about the uptake mechanism involved, how it is regulated, and how it is affected by internal and external factors. We addressed these issues using the mouse-derived pancreatic beta-TC-6 cells and freshly isolated mouse and human primary pancreatic beta cells as models. The results showed biotin uptake by pancreatic beta-TC-6 cells occurs via a Na ϩ -dependent, carrier-mediated process, that is sensitive to desthiobiotin, as well as to pantothenic acid and lipoate; the process is also saturable as a function of concentration (apparent K m ϭ 22.24 Ϯ 5.5 M). These cells express the sodium-dependent multivitamin transporter (SMVT), whose knockdown (with doxycycline-inducible shRNA) led to a sever inhibition in biotin uptake. Similarly, uptake of biotin by mouse and human primary pancreatic islets is Na ϩ -dependent and carrier-mediated, and both cell types express SMVT. Biotin uptake by pancreatic beta-TC-6 cells is also adaptively regulated (via transcriptional mechanism) by extracellular substrate level. Chronic treatment of pancreatic beta-TC-6 cells with bacterial lipopolysaccharides (LPS) leads to inhibition in biotin uptake. This inhibition is mediated via a Toll-Like receptor 4-mediated process and involves a decrease in membrane expression of SMVT. These findings show, for the first time, that pancreatic beta cells/islets take up biotin via a specific and regulated carrier-mediated process, and that the process is sensitive to the effect of LPS.biotin; pancreatic beta cells; biotin uptake mechanism; transport regulation THE WATER-SOLUBLE VITAMIN BIOTIN, also known as vitamin B7 or vitamin H, is required for normal cellular functions, growth, and development. Biotin acts as a cofactor (as a carboxyl carrier) for five carboxylases that catalyze indispensable steps in intermediate metabolism including gluconeogenesis and fatty acid metabolism (reviewed in Refs. 34, 35). Emerging evidences also point to a role for biotin in normal immune function and in the regulation of gene expression (reviewed in Refs. 24,29). In reference to the latter, biotin status has been shown to influence the expression of more than 2,000 human genes, at both the transcriptional and post-transcriptional levels (3, 30, 44). The affected genes include those that are critical for maintaining the differentiated phenotype of pancreatic beta cells, preservation of their mass (i.e., their proportion), and for insulin secretion (3,30,38,44). In reference to the latter, the vitamin has been shown to increases the expression of pancreatic and duodenal homeobox 1 (Pdx-1) (44), a critical transcri...

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Biotin uptake by mouse and human pancreatic beta cells/islets: a regulated, lipopolysaccharide-sensitive carrier-mediated process

Ghosal

Sekar

Said

2014

American Journal of Physiology-Gastrointestinal and Liver Physi

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“…A positive effect of biotin on insulin secretion has been reported (RomeroNavarro, G. et al 1999;Sone, H. et al 2000;Sone, H. et al 1999;Vilches-Flores, A. et al 2009). Studies by our group (Romero-Navarro, G. et al 1999;Vilches-Flores, A. et al 2009) and others (Sone, H. et al 2000;Sone, H. et al 1999) have revealed that glucose-stimulated insulin secretion increases in response to acute exposure to pharmacological doses of biotin in either primary cultured islets (Romero-Navarro, G. et al 1999), perifused pancreas (Sone, H. et al 1999) or perifused islets (Sone, H. et al 2000). This effect of biotin on insulin secretion also appears to be dose-dependent (Sone, H. et al 1999).…”

Section: Biotinmentioning

confidence: 92%

“…1998), this is likely the enzyme mediating cGMP actions on insulin secretion. It has also been shown that PKG activity is necessary to increase ATP content in response to cGMP (Vilches-Flores, A. et al 2009), and that glucose produces small increases in islet cGMP content (Laychock, S.G. et al 1991;Schmidt, H.H. et al 1992).…”

Section: The Cgmp/pkg Pathwaymentioning

confidence: 99%

“…The increase of ATP induces insulin secretion via ATP-sensitive potassium channels. Insulin, in an autocrine manner, activates PI3K/Akt signaling, which increases pancreatic glucokinase mRNA expression (Vilches-Flores, A. et al 2009). Although the acute effect of biotin on in vitro insulin secretion has been well documented, further studies addressing the effect of this vitamin on in vivo models, resembling the actual doses and periods of treatment currently recommended for diabetes treatment, need to be done.…”

Section: Biotinmentioning

confidence: 99%

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Beta-Cell Function and Failure in Type 1 Diabetes

Lazo-de-la-Vega-Monroy¹,

Fernández-Mejía²

2011

Type 1 Diabetes - Pathogenesis, Genetics and Immunotherapy

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The hypotriglyceridemic effect of biotin supplementation involves increased levels of cGMP and AMPK activation

Aguilera‐Méndez

Fernández-Mejía

2012

BioFactors

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In addition to its role as a carboxylase cofactor, biotin modifies gene expression and has manifold effects on systemic processes. Several studies have shown that biotin supplementation reduces hypertriglyceridemia. We have previously reported that this effect is related to decreased expression of lipogenic genes. In the present work, we analyzed signaling pathways and posttranscriptional mechanisms involved in the hypotriglyceridemic effects of biotin. Male BALB/cAnN Hsd mice were fed a control or a biotin-supplemented diet (1.76 or 97.7 mg of free biotin/kg diet, respectively for 8 weeks after weaning. The abundance of mature sterol regulatory element-binding protein (SREBP-1c), fatty-acid synthase (FAS), total acetyl-CoA carboxylase-1 (ACC-1) and its phosphorylated form, and AMP-activated protein kinase (AMPK) were evaluated in the liver. We also determined the serum triglyceride concentrations and the hepatic levels of triglycerides and cyclic GMP (cGMP). Compared to the control group, biotin-supplemented mice had lower serum and hepatic triglyceride concentrations. Biotin supplementation increased the levels of cGMP and the phosphorylated forms of AMPK and ACC-1 and decreased the abundance of the mature form of SREBP-1c and FAS. These data provide evidence that the mechanisms by which biotin supplementation reduces lipogenesis involve increased cGMP content and AMPK activation. In turn, these changes lead to augmented ACC-1 phosphorylation and decreased expression of both the mature form of SREBP-1c and FAS. Our results demonstrate for the first time that AMPK is involved in the effects of biotin supplementation and offer new insights into the mechanisms of biotin-mediated hypotriglyceridemic effects.

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Biotin increases glucokinase expression via soluble guanylate cyclase/protein kinase G, adenosine triphosphate production and autocrine action of insulin in pancreatic rat islets☆

Cited by 29 publications

References 63 publications

Biotin uptake by mouse and human pancreatic beta cells/islets: a regulated, lipopolysaccharide-sensitive carrier-mediated process

Biotin uptake by mouse and human pancreatic beta cells/islets: a regulated, lipopolysaccharide-sensitive carrier-mediated process

Beta-Cell Function and Failure in Type 1 Diabetes

The hypotriglyceridemic effect of biotin supplementation involves increased levels of cGMP and AMPK activation

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