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Diabetes mellitus and expression of the enterocyte renin-angiotensin system: implications for control of glucose transport across the brush border membrane.
Am J Physiol Cell Physiol 2009; 297(3):C601-10AJ

Abstract

Streptozotocin-induced (Type 1) diabetes mellitus (T1DM) in rats promotes jejunal glucose transport, but the trigger for this response remains unclear. Our recent work using euglycemic rats has implicated the enterocyte renin-angiotensin system (RAS) in control of sodium-dependent glucose transporter (SGLT1)-mediated glucose uptake across the jejunal brush border membrane (BBM). The aim of the present study was to examine whether expression of enterocyte RAS components is influenced by T1DM. The effects of mucosal addition of angiotensin II (AII) on [(14)C]-D-glucose uptake by everted diabetic jejunum was also determined. Two-week diabetes caused a fivefold increase in blood glucose level and reduced mRNA and protein expression of AII type 1 (AT(1)) and AT(2) receptors and angiotensin-converting enzyme in isolated jejunal enterocytes. Angiotensinogen expression was, however, stimulated by diabetes while renin was not detected in either control or diabetic enterocytes. Diabetes stimulated glucose uptake into everted jejunum by 58% and increased the BBM expression of SGLT1 and facilitated glucose transporter 2 (GLUT2) proteins, determined by Western blotting by 25% and 135%, respectively. Immunohistochemistry confirmed an enhanced BBM expression of GLUT2 in diabetes and also showed that this was due to translocation of the transporter from the basolateral membrane to BBM. AII (5 microM) or L-162313 (1 microM), a nonpeptide AII analog, decreased glucose uptake by 18% and 24%, respectively, in diabetic jejunum. This inhibitory action was fully accountable by an action on SGLT1-mediated transport and was abolished by the AT(1) receptor antagonist losartan (1 microM). The decreased inhibitory action of AII on in vitro jejunal glucose uptake in diabetes compared with that noted previously in jejunum from normal animals is likely to be due to reduced RAS expression in diabetic enterocytes, together with a disproportionate increase in GLUT2, compared with SGLT1 expression at the BBM.

Authors+Show Affiliations

School of Biomedical Sciences, Faculty of Medicine, The Chinese Univ. of Hong Kong, Shatin, N.T., Hong Kong, China.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19535516

Citation

Wong, Tung Po, et al. "Diabetes Mellitus and Expression of the Enterocyte Renin-angiotensin System: Implications for Control of Glucose Transport Across the Brush Border Membrane." American Journal of Physiology. Cell Physiology, vol. 297, no. 3, 2009, pp. C601-10.
Wong TP, Debnam ES, Leung PS. Diabetes mellitus and expression of the enterocyte renin-angiotensin system: implications for control of glucose transport across the brush border membrane. Am J Physiol, Cell Physiol. 2009;297(3):C601-10.
Wong, T. P., Debnam, E. S., & Leung, P. S. (2009). Diabetes mellitus and expression of the enterocyte renin-angiotensin system: implications for control of glucose transport across the brush border membrane. American Journal of Physiology. Cell Physiology, 297(3), pp. C601-10. doi:10.1152/ajpcell.00135.2009.
Wong TP, Debnam ES, Leung PS. Diabetes Mellitus and Expression of the Enterocyte Renin-angiotensin System: Implications for Control of Glucose Transport Across the Brush Border Membrane. Am J Physiol, Cell Physiol. 2009;297(3):C601-10. PubMed PMID: 19535516.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Diabetes mellitus and expression of the enterocyte renin-angiotensin system: implications for control of glucose transport across the brush border membrane. AU - Wong,Tung Po, AU - Debnam,Edward S, AU - Leung,Po Sing, Y1 - 2009/06/17/ PY - 2009/6/19/entrez PY - 2009/6/19/pubmed PY - 2009/10/6/medline SP - C601 EP - 10 JF - American journal of physiology. Cell physiology JO - Am. J. Physiol., Cell Physiol. VL - 297 IS - 3 N2 - Streptozotocin-induced (Type 1) diabetes mellitus (T1DM) in rats promotes jejunal glucose transport, but the trigger for this response remains unclear. Our recent work using euglycemic rats has implicated the enterocyte renin-angiotensin system (RAS) in control of sodium-dependent glucose transporter (SGLT1)-mediated glucose uptake across the jejunal brush border membrane (BBM). The aim of the present study was to examine whether expression of enterocyte RAS components is influenced by T1DM. The effects of mucosal addition of angiotensin II (AII) on [(14)C]-D-glucose uptake by everted diabetic jejunum was also determined. Two-week diabetes caused a fivefold increase in blood glucose level and reduced mRNA and protein expression of AII type 1 (AT(1)) and AT(2) receptors and angiotensin-converting enzyme in isolated jejunal enterocytes. Angiotensinogen expression was, however, stimulated by diabetes while renin was not detected in either control or diabetic enterocytes. Diabetes stimulated glucose uptake into everted jejunum by 58% and increased the BBM expression of SGLT1 and facilitated glucose transporter 2 (GLUT2) proteins, determined by Western blotting by 25% and 135%, respectively. Immunohistochemistry confirmed an enhanced BBM expression of GLUT2 in diabetes and also showed that this was due to translocation of the transporter from the basolateral membrane to BBM. AII (5 microM) or L-162313 (1 microM), a nonpeptide AII analog, decreased glucose uptake by 18% and 24%, respectively, in diabetic jejunum. This inhibitory action was fully accountable by an action on SGLT1-mediated transport and was abolished by the AT(1) receptor antagonist losartan (1 microM). The decreased inhibitory action of AII on in vitro jejunal glucose uptake in diabetes compared with that noted previously in jejunum from normal animals is likely to be due to reduced RAS expression in diabetic enterocytes, together with a disproportionate increase in GLUT2, compared with SGLT1 expression at the BBM. SN - 1522-1563 UR - https://www.unboundmedicine.com/medline/citation/19535516/Diabetes_mellitus_and_expression_of_the_enterocyte_renin_angiotensin_system:_implications_for_control_of_glucose_transport_across_the_brush_border_membrane_ L2 - http://www.physiology.org/doi/full/10.1152/ajpcell.00135.2009?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -