Expression of glucose transporter‐2, glucokinase and mitochondrial glycerolphosphate dehydrogenase in pancreatic islets during rat ontogenesis

García-Flores, Marta; Zueco, José Antonio; Arenas, Joaquı́n; Blázquez, Enrique

doi:10.1046/j.0014-2956.2002.02625.x

Cited by 16 publications

(17 citation statements)

References 42 publications

(45 reference statements)

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“…It has been previously shown that Glut2 messages are increased in adult islets compared with those in the postnatal young mice [34,35]; here we confirmed this finding showing higher gene expression of Glut2 in adult compared to P5 and P8 islets (Fig. 6B).…”

supporting

confidence: 81%

Glucocorticoid Signaling Enhances Expression of Glucose-Sensing Molecules in Immature Pancreatic Beta-Like Cells Derived from Murine Embryonic Stem Cells In Vitro

Ghazalli

Walker

et al. 2018

Stem Cells and Development

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Pluripotent stem cells may serve as an alternative source of beta-like cells for replacement therapy of type 1 diabetes; however, the beta-like cells generated in many differentiation protocols are immature. The maturation of endogenous beta cells involves an increase in insulin expression starting in late gestation and a gradual acquisition of the abilities to sense glucose and secrete insulin by week 2 after birth in mice; however, what molecules regulate these maturation processes are incompletely known. In this study, we aim to identify small molecules that affect immature beta cells. A cell-based assay, using pancreatic beta-like cells derived from murine embryonic stem (ES) cells harboring a transgene containing an insulin 1-promoter driven enhanced green fluorescent protein reporter, was used to screen a compound library (NIH Clinical Collection-003). Cortisone, a glucocorticoid, was among five positive hit compounds. Quantitative reverse transcription-polymerase chain reaction analysis revealed that glucocorticoids enhance the gene expression of not only insulin 1 but also glucose transporter-2 (Glut2; Slc2a2) and glucokinase (Gck), two molecules important for glucose sensing. Mifepristone, a pharmacological inhibitor of glucocorticoid receptor (GR) signaling, reduced the effects of glucocorticoids on Glut2 and Gck expression. The effects of glucocorticoids on ES-derived cells were further validated in immature primary islets. Isolated islets from 1-week-old mice had an increased Glut2 and Gck expression in response to a 4-day treatment of exogenous hydrocortisone in vitro. Gene deletion of GR in beta cells using rat insulin 2 promoter-driven Cre crossed with GR flox/flox mice resulted in a reduced gene expression of Glut2, but not Gck, and an abrogation of insulin secretion when islets were incubated in 0.5 mM d-glucose and stimulated by 17 mM d-glucose in vitro. These results demonstrate that glucocorticoids positively regulate glucose sensors in immature murine beta-like cells.

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supporting

confidence: 81%

Glucocorticoid Signaling Enhances Expression of Glucose-Sensing Molecules in Immature Pancreatic Beta-Like Cells Derived from Murine Embryonic Stem Cells In Vitro

Ghazalli

Walker

et al. 2018

Stem Cells and Development

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“…This could be due to a number of factors. A good possibility is the lack of sufficient glucose transporters (GLUT2), as has been previously observed (11,13). As shown in Fig.…”

Section: Resultsmentioning

confidence: 66%

Physiological development of insulin secretion, calcium channels, and GLUT2 expression of pancreatic rat β-cells

Navarro-Tableros¹,

Fiordelisio²,

Hernández‐Cruz³

et al. 2007

American Journal of Physiology-Endocrinology and Metabolism

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Insulin secretion in mature β-cells increases vigorously when extracellular glucose concentration rises. Glucose-stimulated insulin secretion depends on Ca2+ influx through voltage-gated Ca2+ channels. During fetal development, this structured response is not well established, and it is after birth that β-cells acquire glucose sensitivity and a robust secretion. We compared some elements of glucose-induced insulin secretion coupling in β-cells obtained from neonatal and adult rats and found that neonatal cells are functionally immature compared with adult cells. We observed that neonatal cells secrete less insulin and cannot sense changes in extracellular glucose concentrations. This could be partially explained because in neonates Ca2+ current density and synthesis of mRNA α1 subunit Ca2+ channel are lower than in adult cells. Interestingly, immunostaining for α1B, α1C, and α1D subunits in neonatal cells is similar in cytoplasm and plasma membrane, whereas it occurs predominantly in the plasma membrane in adult cells. We also observed that GLUT2 expression in adult β-cells is mostly located in the membrane, whereas in neonatal cells glucose transporters are predominantly in the cytoplasm. This could explain, in part, the insensitivity to extracellular glucose in neonatal β-cells. Understanding neonatal β-cell physiology and maturation contributes toward a better comprehension of type 2 diabetes physiopathology, where alterations in β-cells include diminished L-type Ca2+ channels and GLUT2 expression that results in an insufficient insulin secretion.

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Section: Discussionmentioning

confidence: 99%

“…GLUT2 mRNA expression was low in islets isolated from fetal or neonatal rats, but increased to adult levels during the suckling period, whereas GLUT2 protein levels remained low until adulthood [10,11]. GCK mRNA was already at adult levels by late fetal life [10,11]. In an immunohistochemical study, GLUT2 was restricted to pancreatic epithelium at early stages of rat fetal development and few beta cells were positive for GLUT2 until gestational day 17 [12].…”

Section: Discussionmentioning

confidence: 99%

Low levels of glucose transporters and % MathType!Translator!2!1!AMS LaTeX.tdl!TeX -- AMS-LaTeX! % MathType!MTEF!2!1!+- % feaaeaart1ev0aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbbjxAHX % garmWu51MyVXgatuuDJXwAK1uy0HwmaeHbfv3ySLgzG0uy0Hgip5wz % aebbnrfifHhDYfgasaacH8qrps0lbbf9q8WrFfeuY-Hhbbf9v8qqaq % Fr0xc9pk0xbba9q8WqFfea0-yr0RYxir-Jbba9q8aq0-yq-He9q8qq % Q8frFve9Fve9Ff0dmeaabaqaciGacaGaaeqabaWaaeWaeaaakeaaca % WGlbWaa0baaSqaaiaadgeacaWGubGaamiuaaqaaiabgUcaRaaaaaa!3BE3! $$ K^{ + }_{{ATP}} $$ channels in human panc

et al. 2007

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Aims/hypothesis Although cells expressing insulin are detected early in human fetal development, islets isolated from fetal pancreases show poor insulin secretory responses to glucose, which may be the result of deficient glucose sensing. We have used dual and triple immunolabelling of human fetal and adult pancreas sections to investigate the presence of proteins that participate in glucose sensing in the pancreatic beta cell, namely glucose transporter 1 (GLUT 1, also known as SLC2A1), glucose transporter 2 (GLUT2, also known as SLC2A2), glucokinase (GCK) and inwardly rectifying K + channel (KIR6.2, also known as KCNJ11) and sulphonylurea receptor 1 (SUR1, also known as ABCC8) subunits of ATP-sensitive K + channels (K þ ATP channels). Materials and methods Pancreases obtained with ethical approval from human fetuses from 11 to 36 weeks of gestation, from infants and from adults were formalin-fixed and embedded in paraffin. Sections were labelled with antibodies to proteins of interest. Co-production of antigens was examined by dual and triple immunolabelling. Results GLUT2 and K þ ATP channel labelling was detected in the 11-week pancreas, but largely within the pancreatic epithelium, whereas no labelling for GLUT1 was observed. From 15 weeks, GLUT1, GCK and K þ ATP channel labelling was detected in an increasing proportion of insulin-positive cells and epithelial labelling with K þ ATP channel antibodies diminished. GLUT2 was seen in the majority of beta cells only after 7 months of age. Conclusions/interpretation The results demonstrate that only a subpopulation of beta cells in the human fetal pancreas produce all key elements of the glucose-sensing apparatus, which may contribute to poor secretory responses in early life.

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Expression of glucose transporter‐2, glucokinase and mitochondrial glycerolphosphate dehydrogenase in pancreatic islets during rat ontogenesis

Cited by 16 publications

References 42 publications

Glucocorticoid Signaling Enhances Expression of Glucose-Sensing Molecules in Immature Pancreatic Beta-Like Cells Derived from Murine Embryonic Stem Cells In Vitro

Glucocorticoid Signaling Enhances Expression of Glucose-Sensing Molecules in Immature Pancreatic Beta-Like Cells Derived from Murine Embryonic Stem Cells In Vitro

Physiological development of insulin secretion, calcium channels, and GLUT2 expression of pancreatic rat β-cells

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