%0 Journal Article %1 muhlemann2018altered %A Muhlemann, M. %A Zdzieblo, D. %A Friedrich, A. %A Berger, C. %A Otto, C. %A Walles, H. %A Koepsell, H. %A Metzger, M. %D 2018 %J Mol Metab %K Animals myOwn %P 67-76 %R 10.1016/j.molmet.2018.05.011 %T Altered pancreatic islet morphology and function in SGLT1 knockout mice on a glucose-deficient, fat-enriched diet %U https://www.ncbi.nlm.nih.gov/pubmed/29859847 %V 13 %X OBJECTIVES: Glycemic control by medical treatment represents one therapeutic strategy for diabetic patients. The Na+-d-glucose cotransporter 1 (SGLT1) is currently of high interest in this context. SGLT1 is known to mediate glucose absorption and incretin secretion in the small intestine. Recently, inhibition of SGLT1 function was shown to improve postprandial hyperglycemia. In view of the lately demonstrated SGLT1 expression in pancreatic islets, we investigated if loss of SGLT1 affects islet morphology and function. METHODS: Effects associated with the loss of SGLT1 on pancreatic islet (cyto) morphology and function were investigated by analyzing islets of a SGLT1 knockout mouse model, that were fed a glucose-deficient, fat-enriched diet (SGLT1(-/-)-GDFE) to circumvent the glucose-galactose malabsorption syndrome. To distinguish diet- and Sglt1(-/-)-dependent effects, wildtype mice on either standard chow (WT-SC) or the glucose-free, fat-enriched diet (WT-GDFE) were used as controls. Feeding a glucose-deficient, fat-enriched diet further required the analysis of intestinal SGLT1 expression and function under diet-conditions. RESULTS: Consistent with literature, our data provide evidence that small intestinal SGLT1 mRNA expression and function is regulated by nutrition. In contrast, pancreatic SGLT1 mRNA levels were not affected by the applied diet, suggesting different regulatory mechanisms for SGLT1 in diverse tissues. Morphological changes such as increased islet sizes and cell numbers associated with changes in proliferation and apoptosis and alterations of the beta- and alpha-cell population are specifically observed for pancreatic islets of SGLT1(-/-)-GDFE mice. Glucose stimulation revealed no insulin response in SGLT1(-/-)-GDFE mice while WT-GDFE mice displayed only a minor increase of blood insulin. Irregular glucagon responses were observed for both, SGLT1(-/-)-GDFE and WT-GDFE mice. Further, both animal groups showed a sustained release of GLP-1 compared to WT-SC controls. CONCLUSION: Loss or impairment of SGLT1 results in abnormal pancreatic islet (cyto)morphology and disturbed islet function regarding the insulin or glucagon release capacity from beta- or alpha-cells, respectively. Consequently, our findings propose a new, additional role for SGLT1 maintaining proper islet structure and function.

@article{muhlemann2018altered, abstract = {OBJECTIVES: Glycemic control by medical treatment represents one therapeutic strategy for diabetic patients. The Na+-d-glucose cotransporter 1 (SGLT1) is currently of high interest in this context. SGLT1 is known to mediate glucose absorption and incretin secretion in the small intestine. Recently, inhibition of SGLT1 function was shown to improve postprandial hyperglycemia. In view of the lately demonstrated SGLT1 expression in pancreatic islets, we investigated if loss of SGLT1 affects islet morphology and function. METHODS: Effects associated with the loss of SGLT1 on pancreatic islet (cyto) morphology and function were investigated by analyzing islets of a SGLT1 knockout mouse model, that were fed a glucose-deficient, fat-enriched diet (SGLT1(-/-)-GDFE) to circumvent the glucose-galactose malabsorption syndrome. To distinguish diet- and Sglt1(-/-)-dependent effects, wildtype mice on either standard chow (WT-SC) or the glucose-free, fat-enriched diet (WT-GDFE) were used as controls. Feeding a glucose-deficient, fat-enriched diet further required the analysis of intestinal SGLT1 expression and function under diet-conditions. RESULTS: Consistent with literature, our data provide evidence that small intestinal SGLT1 mRNA expression and function is regulated by nutrition. In contrast, pancreatic SGLT1 mRNA levels were not affected by the applied diet, suggesting different regulatory mechanisms for SGLT1 in diverse tissues. Morphological changes such as increased islet sizes and cell numbers associated with changes in proliferation and apoptosis and alterations of the beta- and alpha-cell population are specifically observed for pancreatic islets of SGLT1(-/-)-GDFE mice. Glucose stimulation revealed no insulin response in SGLT1(-/-)-GDFE mice while WT-GDFE mice displayed only a minor increase of blood insulin. Irregular glucagon responses were observed for both, SGLT1(-/-)-GDFE and WT-GDFE mice. Further, both animal groups showed a sustained release of GLP-1 compared to WT-SC controls. CONCLUSION: Loss or impairment of SGLT1 results in abnormal pancreatic islet (cyto)morphology and disturbed islet function regarding the insulin or glucagon release capacity from beta- or alpha-cells, respectively. Consequently, our findings propose a new, additional role for SGLT1 maintaining proper islet structure and function.}, added-at = {2024-02-15T15:08:22.000+0100}, author = {Muhlemann, M. and Zdzieblo, D. and Friedrich, A. and Berger, C. and Otto, C. and Walles, H. and Koepsell, H. and Metzger, M.}, biburl = {https://www.bibsonomy.org/bibtex/29146080ebcb3b845f3aa09f3b0185448/jvsi_all}, doi = {10.1016/j.molmet.2018.05.011}, interhash = {d19f526cf93e1fb8a3c3a7a8897b8216}, intrahash = {9146080ebcb3b845f3aa09f3b0185448}, issn = {2212-8778 (Electronic) 2212-8778 (Linking)}, journal = {Mol Metab}, keywords = {Animals myOwn}, note = {Muhlemann, Markus Zdzieblo, Daniela Friedrich, Alexandra Berger, Constantin Otto, Christoph Walles, Heike Koepsell, Hermann Metzger, Marco eng Research Support, Non-U.S. Gov't Germany 2018/06/04 Mol Metab. 2018 Jul;13:67-76. doi: 10.1016/j.molmet.2018.05.011. Epub 2018 May 23.}, pages = {67-76}, timestamp = {2024-02-15T15:08:22.000+0100}, title = {Altered pancreatic islet morphology and function in SGLT1 knockout mice on a glucose-deficient, fat-enriched diet}, type = {Journal Article}, url = {https://www.ncbi.nlm.nih.gov/pubmed/29859847}, volume = 13, year = 2018 }