Effect of high‐fat diet on glucose homeostasis and gene expression in glucokinase knockout mice

Gorman, Tracy; Hope, David; Brownlie, R. P.; Yu, Alice; Gill, Derek; Löfvenmark, J.; Wedin, Marianne; Mayers, Rachel M.; Snaith, Michael; Smith, David M.

doi:10.1111/j.1463-1326.2007.00819.x

Cited by 30 publications

(45 citation statements)

References 41 publications

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“…Table 1 summarises the data for those genes in which changes were observed, either greater than twofold or statistically significant (for full gene list, see Gorman et al (2008)). A marked increase in insulin gene expression was observed, consistent with the individual gene Taqman.…”

Section: Gka71 Is a Potent Activator Of Human Pancreatic Gk And Acutementioning

confidence: 99%

“…Male C57Bl/6J mice were 8-10 weeks of age (22-24 g) and male Hannover Wistar rats 8-9 weeks of age (230-260 g). Male global heterozygous GK knockout (gk del/wt ) and wild-type (gk wt/wt ) mice were used between 10 and 16 weeks of age; these animals were generated as described previously (Gorman et al 2008). All procedures were carried out in accordance with the Animals (Scientific Procedures) Act 1986.…”

Section: Experimental Animals and Islet Isolationmentioning

confidence: 99%

“…RNA isolation and gene expression analysis were carried out as described previously (Gorman et al 2008).…”

Section: Rna Isolation and Reverse Transcriptionmentioning

confidence: 99%

“…'Assay on demand' primer/probe mixes (Applied Biosystems) were used for analysis of rat samples: insulin (Rn01774648), GLUT2 (Rn00563565), hypoxanthine phosphoribosyltransferase (HPRT) (Rn01527838), cyclophilin (Rn00690933), b-glucuronidase (Rn00566655), IAPP (Rn00561411), PDX1 (Rn00755591), GK (Rn00561265), PC1 (Rn00 567266) and CEBPb (Rn00824635). Samples from the C57Bl/6J chronic islet experiment were used to perform Taqman low-density arrays (TLDA), which were carried out as described previously (Gorman et al 2008).…”

Section: Gene Expression Analysismentioning

confidence: 99%

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Upregulation of β-cell genes and improved function in rodent islets following chronic glucokinase activation

Gill¹,

Brocklehurst²,

Brown³

et al. 2011

Journal of Molecular Endocrinology

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Glucokinase (GK) plays a critical role in controlling blood glucose; GK activators have been shown to stimulate insulin secretion acutely both in vitro and in vivo. Sustained stimulation of insulin secretion could potentially lead to b-cell exhaustion; this study examines the effect of chronic GK activation on b-cells. Gene expression and insulin secretion were measured in rodent islets treated in vitro with GKA71 for 72 h. Key b-cell gene expression was measured in rat, mouse and global GK heterozygous knockout mouse islets (gk del/wt ). Insulin secretion, after chronic exposure to GKA71, was measured in perifused rat islets. GKA71 acutely increased insulin secretion in rat islets in a glucose-dependent manner. Chronic culture of mouse islets with GKA71 in 5 mmol/l glucose significantly increased the expression of insulin, IAPP, GLUT2, PDX1 and PC1 and decreased the expression of C/EBPb compared with 5 mmol/l glucose alone. Similar increases were shown for insulin, GLUT2, IAPP and PC1 in chronically treated rat islets. Insulin mRNA was also increased in GKA71-treated gk del/wt islets. No changes in GK mRNA were observed. Glucose-stimulated insulin secretion was improved in perifused rat islets following chronic treatment with GKA71. This was associated with a greater insulin content and GK protein level. Chronic treatment of rodent islets with GKA71 showed an upregulation of key b-cell genes including insulin and an increase in insulin content and GK protein compared with glucose alone.

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Section: Gka71 Is a Potent Activator Of Human Pancreatic Gk And Acutementioning

confidence: 99%

Section: Experimental Animals and Islet Isolationmentioning

confidence: 99%

“…RNA isolation and gene expression analysis were carried out as described previously (Gorman et al 2008).…”

Section: Rna Isolation and Reverse Transcriptionmentioning

confidence: 99%

Section: Gene Expression Analysismentioning

confidence: 99%

See 2 more Smart Citations

Upregulation of β-cell genes and improved function in rodent islets following chronic glucokinase activation

Gill¹,

Brocklehurst²,

Brown³

et al. 2011

Journal of Molecular Endocrinology

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show abstract

“…Since the report by Grimsby et al in 2003 [5], several glucokinase activators (GKAs) have been developed, and these have been shown to lower blood glucose in several animal models of type 2 diabetes [5][6][7][8][9][10][11][12]. In a study of beta cell function, it was reported that a GKA stimulated insulin secretion in a Ca 2+ -dependent manner in rodent islets and MIN6 cells [13], and we and others have reported that GKAs promoted beta cell proliferation and increased production of IRS2 [11,14], which is critically required for beta cell growth and survival [3,[15][16][17].…”

Section: Introductionmentioning

confidence: 99%

Control of beta cell function and proliferation in mice stimulated by small-molecule glucokinase activator under various conditions

et al. 2012

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Aims/hypothesis We investigated changes in the expression of genes involved in beta cell function and proliferation in mouse islets stimulated with glucokinase activator (GKA) in order to elucidate the mechanisms by which GKA stimulates beta cell function and proliferation. Methods Islets isolated from mice were used to investigate changes in the expression of genes related to beta cell function and proliferation stimulated by GKA. In addition, Irs2 knockout (Irs2 −/− ) mice on a high-fat diet or a high-fat diet containing GKA were used to investigate the effects of GKA on beta cell proliferation in vivo. Results In wild-type mice, Irs2 and Pdx1 expression was increased by GKA. In Irs2 −/− mice, GKA administration increased the glucose-stimulated secretion of insulin and Pdx1 expression, but not beta cell proliferation. It was particularly noteworthy that oxidative stress inhibited the upregulation of the Irs2 and Pdx1 genes induced by GKA. Moreover, whereas neither GKA alone nor exendin-4 alone upregulated the expression of Irs2 and Pdx1 in the islets of db/db mice, prior administration of exendin-4 to the mice caused GKA to increase the expression of these genes.Conclusions/interpretation GKA-stimulated IRS2 production affected beta cell proliferation but not beta cell function. Oxidative stress diminished the effects of GKA on the changes in expression of genes involved in beta cell function and proliferation. A combination of GKA and an incretin-related agent might therefore be effective in therapy.

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Current literature in diabetes

2009

Diabetes Metabolism Res

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In order to keep subscribers up‐to‐date with the latest developments in their field, John Wiley & Sons are providing a current awareness service in each issue of the journal. The bibliography contains newly published material in the field of diabetes/metabolism. Each bibliography is divided into 26 sections: 1 Reviews; 2 General; 3 Genetics; 4 Epidemiology; 5 Immunology; 6 Obesity; 7 Prediction and Prevention; 8 Intervention: a) General; b) Care; c) Drug Therapy; d)Economics; e) Gene therapy; f) Nursing; g) Nutrition; h) Surgery; i) Transplantation; 9 Pathology and Complications: a) General; b) Cardiovascular; c) Eye disease; d) Gestational and fetal; e) Neurological; f) Podiatrical; g) Renal; 10 Endocrinology & Metabolism; 11 Experimental Studies; 12 Diagnosis and Techniques. Within each section, articles are listed in alphabetical order with respect to author

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Effect of high‐fat diet on glucose homeostasis and gene expression in glucokinase knockout mice

Cited by 30 publications

References 41 publications

Upregulation of β-cell genes and improved function in rodent islets following chronic glucokinase activation

Upregulation of β-cell genes and improved function in rodent islets following chronic glucokinase activation

Control of beta cell function and proliferation in mice stimulated by small-molecule glucokinase activator under various conditions

Current literature in diabetes

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