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Supratherapeutic Insulin Alters Intracellular pH in Human Kidney Tubular Epithelial Cells
Author(s) -
Kruss Szilvia Ilona,
ValyiNagy Klara,
Setty Suman
Publication year - 2009
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.23.1_supplement.930.7
Subject(s) - insulin , endocrinology , lisinopril , medicine , intracellular , kidney , insulin resistance , carbohydrate metabolism , metabolic syndrome , diabetes mellitus , chemistry , biochemistry , blood pressure , angiotensin converting enzyme
Background The profile of metabolic syndrome includes high fasting sugars and hypertension. Intracellular pH (pHi) is vital for the maintenance of the normal metabolic function of human kidney tubular epithelial cells (HK‐2). In the present study we investigated whether high glucose levels and two common agents that are used to treat metabolic syndrome, insulin and lisinopril have an effect on pHi in cultured HK‐2 cells. Methods Immortalized tubular kidney HK‐2 cells were cultured in media containing normal (5 mM) or increased (25 mM) amounts of glucose. Cultures were then exposed to therapeutic or supratherapeutic (3 times higher) doses of insulin and lisinopril and consequent changes in pHi were determined using a SNARF 5‐(and‐6)‐carboxy SNARF®‐1, acetoxymethyl ester agent (Invitrogen, Carlsbad) at 8 days after treatment. Results pHi was significantly higher (p<.05) in cells treated with 25 mM versus 5 mM glucose. Supratherapeutic insulin treatment was associated with significantly (p<.01) increased pHi relative to cells cultured in normal and increased glucose. Intracellular pH in the supratherapeutic insulin condition was also significantly elevated (p<.01) relative to lisinopril treated cells. Conclusions Increased glucose and supratherapeutic insulin lead to increased (more basic) pHi in human kidney tubular epithelial cells. Altered pHi in these cells may have extensive effects on a variety of cellular functions, including promoting insulin resistance. Furthermore, alkalinic changes could assist the propagation of certain types of cancers which will be the basis of further research in our laboratory.