Diabetes and insulin-induced stimulation of L-arginine transport and nitric oxide synthesis in rabbit isolated gastric glands

Mann G.E.; Sobrevia L.; Fuentes O.; Contreras R.

Keywords: kinetics, model, insulin, stimulation, acid, enzyme, transport, animals, synthesis, histamine, ion, cell, bradykinin, mellitus, synthase, gland, diabetes, experiment, ph, male, stereochemistry, agents, oxide, sodium, methyl, rabbits, rabbit, glands, experimental, stomach, mucosa, inhibitors, article, arginine, ester, polypeptide, concentration, leucine, controlled, animal, hyperpolarization, alloxan, gastric, study, response, amino, priority, cyclic, nonhuman, journal, citrulline, gmp, nitric, Intestinal, n(g), nitroarginine, Mellitus,, phenylalanine, vasoactive, Hypoglycemic, tetraphenylphosphonium, Exocrine

Abstract

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 V(max) 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 nondiabetic glands histamine, vasoactive intestinal peptide, and bradykinin increased caMP levels. The NO synthase inhibitor N(G)-nitro-L-arginine methyl ester (100 μM) 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 nondiabetic 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.

Más información

Título según SCOPUS: Diabetes and insulin-induced stimulation of L-arginine transport and nitric oxide synthesis in rabbit isolated gastric glands
Título de la Revista: JOURNAL OF PHYSIOLOGY-LONDON
Volumen: 498
Número: 3
Editorial: Wiley
Fecha de publicación: 1997
Página de inicio: 787
Página final: 796
Idioma: English
URL: http://www.scopus.com/inward/record.url?eid=2-s2.0-0031050810&partnerID=q2rCbXpz
Notas: SCOPUS