Impaired intestinal and renal glucose transport in PDK-1 hypomorphic mice

Artunc, Ferruh; Rexhepaj, Rexhep; Völkl, Harald; Grahammer, Florian; Remy, Christine; Sandulache, Diana; Nasir, Omaima; Wagner, Carsten A.; Alessi, Dario R.; Läng, Florian

doi:10.1152/ajpregu.00024.2006

Cited by 11 publications

(11 citation statements)

References 47 publications

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“…PDK1 activates the serum and glucocorticoid inducible kinase and protein kinase B PKB/ Akt isoforms [32], which in turn have been shown to regulate a wide variety of transporters [33]. Previous experiments in PDK1 hm mice indeed revealed a decreased activity of glucose transporters [34] and amino acid transporters [35]. Moreover, an increased fluid and food intake has been reported in PDK1 hm mice, while urinary excretion of glutamate and tryptophan, but not 5-hydroxytryptophan is increased in PDK1 hm mice [35].…”

Section: Discussionmentioning

confidence: 95%

Phosphatidylinositide Dependent Kinase Deficiency Increases Anxiety and Decreases GABA and Serotonin Abundance in the Amygdala

Ackermann¹,

Hörtnagl²,

Wolfer³

et al. 2008

Cell Physiol Biochem

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Pathological anxiety is paralleled by deficits in serotonergic and GABAergic neurotransmission in the amygdala. Conversely, anxiety disorders and depression may be reversed by brain-derived neurotrophic factor (BDNF). BDNF signaling involves Phosphatidylinositol 3-Kinase / 3-phosphoinositide-dependent protein kinase 1 (PI3K/PDK1). We thus hypothesized that impaired function of PDK1 might be associated with increased anxiety and concomitant neurotransmitter changes. Here we used the hypomorphic PDK1^hm mouse to investigate anxiety behavior in different settings: PDK1^hm mice differed from Wt littermates PDK1^WT in several behavioral measures related to anxiety and exploration, namely in the open field, dark-light box, O-maze and startle response. Further we analyzed the brain substrate underlying this phenotype and found significantly decreased GABA, taurine and serotonin concentrations in the amygdala and olfactory bulb of PDK1^hm mice, while BDNF and nerve growth factor (NGF) concentrations were not significantly different between PDK1^hm and PDK1^WT mice. These results suggest that impaired PI3K signaling in the PDK1^hm mouse reduces concentrations of GABA and serotonin in anxiety related brain regions and can serve as a molecular substrate for behavior indicative for anxious and depressive-like mood states.

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Section: Discussionmentioning

confidence: 95%

Phosphatidylinositide Dependent Kinase Deficiency Increases Anxiety and Decreases GABA and Serotonin Abundance in the Amygdala

Ackermann¹,

Hörtnagl²,

Wolfer³

et al. 2008

Cell Physiol Biochem

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“…Factors modifying SGLT1 activity include carbohydraterich diet [19], adrenergic innervation [20], insulin [21], glucagon-like peptide 2 [22], cholecystokinin [17], insulinlike growth factors [23], cytosolic Na + [24] and lipopolysaccharides [25]. Moreover, SGLT1 activity is regulated by phosphatidylinositol (PI) 3 kinase [26], the phosphoinositide-dependent kinase 1 (PDK1) [27] as well as the serum-and glucocorticoid-regulated kinase isoforms SGK1 and SGK3 [14,28], kinases regulating the transport of a variety of nutrients and channels [14,[28][29][30][31][32][33]. SGLT1 activity is further subject to downregulation by the 67-kDa-protein RS1 [11].…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, GA treatment prevented the body weight gain following a four week treatment with glucose-rich diet despite similar fluid and food intake in untreated and GA-treated mice. A diet rich in dietary fibres is associated with reduced body weight [27] and prevention of metabolic syndrome [28]. In patients with diabetes mellitus type 2, an increased intake of dietary fibers improved glycemic control and reduced hyperinsulinemia [29].…”

Section: Discussionmentioning

confidence: 99%

Downregulation of Mouse Intestinal Na⁺-coupled Glucose Transporter SGLT1 by Gum Arabic (Acacia Senegal)

Nasir

Artunc

Wang

et al. 2010

Cell Physiol Biochem

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Intestinal Na⁺-coupled glucose transporter SGLT1 determines the rate of glucose transport, which in turn influences glucose-induced insulin release and development of obesity. The present study explored effects of Gum Arabic (GA), a dietary polysaccharide from dried exudates of Acacia Senegal, on intestinal glucose transport and body weight in wild-type C57Bl/6 mice. Treatment with GA (100 g/l) in drinking water for four weeks did not affect intestinal SGLT1 transcript levels but decreased SGLT1 protein abundance in jejunal brush border membrane vesicles. Glucose-induced jejunal short-circuit currents revealed that GA treatment decreased electrogenic glucose transport. Drinking a 20% glucose solution for four weeks significantly increased body weight and fasting plasma glucose concentrations, effects significantly blunted by simultaneous treatment with GA. GA further significantly blunted the increase in body weight, fasting plasma glucose and fasting insulin concentrations during high fat diet. In conclusion, the present observations disclose a completely novel effect of gum arabic, i.e. its ability to decrease intestinal SGLT1 expression and activity and thus to counteract glucose-induced obesity.

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“…SGLT1 activity is influenced by carbohydrate-rich diet [50], adrenergic innervation [51], insulin [52] glucagon-like peptide 2 [53], cholecystokinin [48], and insulin-like growth factors [54]. Signaling of SGLT1 regulation includes phosphatidylinositol (PI) 3 kinase [55], phosphoinositide-dependent kinase 1 (PDK1) [56] as well as the serum-and glucocorticoid-regulated kinase isoforms SGK1 [57,58] and SGK3 [59]. SGLT1 activity is further subject to downregulation by the 67-kDa-protein RS1 [60,61].…”

Section: Extrarenal Effects Of Gamentioning

confidence: 99%

Renal and Extrarenal Effects of Gum Arabic (Acacia Senegal) - What Can be Learned from Animal Experiments?

Nasir

2013

Kidney Blood Press Res

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Gum arabic (GA), a water-soluble dietary fiber rich in Ca²⁺, Mg²⁺ and K⁺, is used in Middle Eastern countries for the treatment of patients with chronic kidney disease. Recent animal experiments shed some light into mechanisms involved in the therapeutic action of GA. According to experiments in healthy mice, GA treatment increases creatinine clearance, enhances renal excretion of ADH, Mg²⁺ and Ca²⁺, decreases plasma phosphate concentration as well as urinary excretion of phosphate and Na⁺. In diabetic mice GA treatment increases urinary Ca²⁺ excretion, and decreases plasma phosphate concentration, plasma urea concentration, urinary flow rate, natriuresis, phosphaturia, glucosuria, proteinuria as well as blood pressure. Extrarenal effects of GA treatment in mice include decreased expression of intestinal Na⁺ coupled glucose carrier SGLT1 with subsequent delay of electrogenic intestinal glucose transport, glucose-induced hyperglycemia, hyperinsulinemia and body weight gain. GA treatment decreases colonic transcription of the angiogenetic factors angiogenin 1, angiogenin 3 and angiogenin 4, of CD38 antigen, aquaporin4, interleukin18, vav-3-oncogene, y⁺-amino acid-transporter, sulfatase1, ubiquitinD and chemokine ligand5. Moreover, GA treatment decreases angiogenin and ß-catenin protein expression. Accordingly, GA treatment counteracts the development of tumors following chemical cancerogenesis. In mouse dendritic cells, antigen-presenting cells linking innate and adaptive immunity, GA treatment modifies maturation and cytokine release. GA treatment further favourably influences the course of murine malaria. The effects of GA treatment on plasma phosphate concentration, blood pressure and proteinuria may prove beneficial in chronic renal failure and diabetic nephropathy. The effect of GA on intestinal glucose transport may be useful in the prophylaxis and treatment of obesity and diabetes, the effect of GA on angiogenin and ß-catenin expression could be exploited for the prophylaxis against colon carcinoma, the effects of GA on angiogenin expression and dendritic cells may be useful in the treatment of inflammatory disease and malaria.

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Impaired intestinal and renal glucose transport in PDK-1 hypomorphic mice

Abstract: . Impaired intestinal and renal glucose transport in PDK-1 hypomorphic mice.

Cited by 11 publications

References 47 publications

Phosphatidylinositide Dependent Kinase Deficiency Increases Anxiety and Decreases GABA and Serotonin Abundance in the Amygdala

Phosphatidylinositide Dependent Kinase Deficiency Increases Anxiety and Decreases GABA and Serotonin Abundance in the Amygdala

Downregulation of Mouse Intestinal Na⁺-coupled Glucose Transporter SGLT1 by Gum Arabic (Acacia Senegal)

Renal and Extrarenal Effects of Gum Arabic (Acacia Senegal) - What Can be Learned from Animal Experiments?

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Impaired intestinal and renal glucose transport in PDK-1 hypomorphic mice

Abstract: . Impaired intestinal and renal glucose transport in PDK-1 hypomorphic mice.

Cited by 11 publications

References 47 publications

Phosphatidylinositide Dependent Kinase Deficiency Increases Anxiety and Decreases GABA and Serotonin Abundance in the Amygdala

Phosphatidylinositide Dependent Kinase Deficiency Increases Anxiety and Decreases GABA and Serotonin Abundance in the Amygdala

Downregulation of Mouse Intestinal Na+-coupled Glucose Transporter SGLT1 by Gum Arabic (Acacia Senegal)

Renal and Extrarenal Effects of Gum Arabic (Acacia Senegal) - What Can be Learned from Animal Experiments?

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Downregulation of Mouse Intestinal Na⁺-coupled Glucose Transporter SGLT1 by Gum Arabic (Acacia Senegal)