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Angiotensin Receptor Blockade Ameliorates Imperative Factors Following a High Glucose Challenge in a Model of Metabolic Syndrome
Author(s) -
Veliz Kenny,
Thorwald Max,
Rodriguez Gema,
Rodriguez Marco Antonio,
Nakano Daisuke,
Nishiyama Akira,
Ortiz Rudy M.
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.1014.24
Subject(s) - medicine , endocrinology , angiotensin ii receptor type 1 , insulin , angiotensin ii , gluconeogenesis , insulin resistance , diabetes mellitus , phosphoenolpyruvate carboxykinase , chemistry , receptor , metabolism , enzyme , biochemistry
The over production of glucose is a key factor in the development of hyperglycemia in diabetes. Angiotensin II (Ang II), increases de novo glucose production by the liver. Blockade of angiotensin II receptor type 1 (AT1) decreases the expression of phosphoenolpyruvate carboxykinase (PEPCK), the rate limiting enzyme in gluconeogenesis, in non‐insulin dependent diabetes. However, whether AT1 activation contributes de novo glucose production by the liver in a metabolic syndrome (MetS) setting/model is not known. To test the hypothesis that activation of AT1 increases the expression of enzymes involved in de novo glucose production by the liver in MetS, hepatic PEPCK protein expression was examined after a 12 hour fast (T0) and 180 and 360 minutes following a glucose challenge (2g/kg) in the following groups of rats (n = 8/group): 1) untreated, lean Long‐Evans Tokushima Otsuka (LETO; 2) untreated, obese Otsuka Long‐Evans Tokushima fatty (OLETF); and 3) OLETF + angiotensin receptor blocker (ARB; 10 mg/kgd in diet for 8 wk; OLETF ARB). We expect an increase in PEPCK expression in OLETF at T0 and that it will remain elevated following the glucose challenge as compared to LETO. We also expect that AT1blockade will reverse this effect. In conclusion, the activation of AT1 in a MetS setting, contributes to glucose intolerance via an upregulation of gluconeogenesis which may ultimately lead to type II diabetes. 1Measurement of systolic blood pressure in lean LETO, insulin resistant OLETF, and OLETF ARB.2Measurements of plasma glucose in lean LETO, insulin resistant OLETF, and OLETF ARB.3Insulin measurements in lean LETO, OLETF, and OLETF ARB.4Mean PEPCK protein expression in lean LETO, insulin resistant OLETF, and OLETF ARB