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

J Physiol. 1997 Feb 1;498 ( Pt 3)(Pt 3):787-96. doi: 10.1113/jphysiol.1997.sp021902.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arginine / metabolism*
  • Citrulline / metabolism
  • Cyclic GMP / metabolism
  • Diabetes Mellitus, Experimental / metabolism*
  • Enzyme Inhibitors / pharmacology
  • Exocrine Glands / metabolism*
  • Gastric Mucosa / metabolism*
  • Hypoglycemic Agents / pharmacology*
  • Insulin / pharmacology*
  • Kinetics
  • Male
  • Nitric Oxide / biosynthesis*
  • Nitric Oxide Synthase / antagonists & inhibitors
  • Nitroarginine / pharmacology
  • Rabbits


  • Enzyme Inhibitors
  • Hypoglycemic Agents
  • Insulin
  • Nitroarginine
  • Citrulline
  • Nitric Oxide
  • Arginine
  • Nitric Oxide Synthase
  • Cyclic GMP