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Diabetes and insulin‐induced stimulation of L‐arginine transport and nitric oxide synthesis in rabbit isolated gastric glands.
Author(s) -
Contreras R,
Fuentes O,
Mann G E,
Sobrevia L
Publication year - 1997
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.1997.sp021902
Subject(s) - medicine , endocrinology , arginine , nitric oxide , vasoactive intestinal peptide , insulin , chemistry , stimulation , extracellular , nitric oxide synthase , streptozotocin , biology , amino acid , diabetes mellitus , biochemistry , neuropeptide , receptor
1. The properties of L‐arginine transport have been characterized and correlated with cGMP production (index of nitric oxide (NO)) in whole gastric glands isolated from non‐diabetic and alloxan‐diabetic rabbits. 2. In non‐diabetic and diabetic glands, transport of L‐arginine was stereoselective, Na+ and pH independent and inhibited by other cationic amino acids. L‐Arginine transport was slightly inhibited by L‐leucine and L‐phenylalanine, but unaffected by other neutral amino acids. 3. Diabetes enhanced the Vmax for saturable L‐arginine transport from 10.7 +/‐ 1.0 to 17.7 +/‐ 0.5 pmol (mg protein)‐1 s‐1, with negligible changes in K(m). 4. Accumulation of the membrane potential‐sensitive probe tetra[3H]phenylphosphonium (TPP+) was increased 2‐fold in diabetic compared with non‐diabetic gastric glands, suggesting a membrane hyperpolarization. 5. Basal intracellular cGMP levels were elevated 2‐fold in diabetic gastric glands, and in non‐diabetic glands histamine, vasoactive intestinal peptide, and bradykinin increased cGMP levels. The NO synthase inhibitor NG‐nitro‐L‐arginine methyl ester (100 microM) abolished basal cGMP accumulation. 6. Addition of extracellular L‐arginine induced a concentration‐dependent increase in cGMP levels in gastric glands isolated from non‐diabetic rabbits, but had no effect on elevated cGMP levels in diabetic glands. 7. Insulin induced a rapid (5 min) concentration‐dependent increase in cGMP levels in non‐diabetic gastric glands, but reduced elevated cGMP levels in diabetic gastric glands. 8. The present study has identified a specific transport system for L‐arginine in gastric glands which resembles the classical system y+. Our findings also provide the first direct evidence that diabetes increases the basal activity of system y+ and NO synthase in gastric glands. The differential modulation of L‐arginine transport by insulin and L‐arginine identified in non‐diabetic and diabetic glands, may be of importance in protecting the gastric mucosa from injuries associated with diabetes.