Faculty Collaboration Database

Restoration of vascular endothelial function in diabetes. Diabetes Res Clin Pract 1996 Jul;31 Suppl:S157-62

Date

07/01/1996

Pubmed ID

8864654

DOI

10.1016/0168-8227(95)01243-5

Scopus ID

2-s2.0-0029739377 (requires institutional sign-in at Scopus site)   8 Citations

Abstract

Nitric oxide (NO) is believed to mediate the phenomenon known as endothelium-dependent relaxation (EDR). NO synthase produces NO from its precursor, arginine (ARG). We have previously demonstrated impaired EDR in diabetic blood vessels. In this study, we investigated a possible mechanism for defective EDR in experimental diabetes and whether pancreatic islet transplantation could reverse established endothelial dysfunction. Streptozotocin-induced diabetic rats were maintained for 8 or 12 weeks. NO-mediated EDR was assessed in isolated thoracic rings ex vivo. A group of untreated diabetic rats received syngeneic islet transplantation at 8 weeks of diabetes and were tested for EDR after 4 weeks of euglycemia. EDR to acetylcholine was impaired in untreated diabetic rings. Endothelium-independent relaxation to nitroglycerin was unaltered. In vitro incubation of diabetic rings with 3 mM L-ARG (but not D-ARG) improved EDR to acetylcholine in rings from 8-week but not 12-week diabetic rats. L-ARG did not alter EDR in control rings nor relaxation to nitroglycerin in control or diabetic rings. Islet transplantation at 8 weeks of diabetes normalized blood glucose, plasma arginine and total glycosylated hemoglobin while restoring normal EDR. In conclusion, a defect in substrate/supply for NO synthesis is acutely reversed by ARG supplementation at early but not at later stages of diabetes. Also, preemptive surgical intervention with islet transplantation prior to the ARG-insensitive phase is an effective strategy to reverse established endothelial dysfunction in diabetes mellitus.

Author List

Pieper GM, Jordan M, Adams MB, Roza AM

Author

Allan Roza MD Emeritus Professor in the Surgery department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Arginine
Blood Glucose
Diabetic Angiopathies
Endothelium, Vascular
Islets of Langerhans Transplantation
Male
Nitric Oxide
Rats
Rats, Inbred Lew
Vasodilation