HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text (PDF) Online-Only Appendix All Versions of this Article: dc07-1198v1 31/1/134    most recent Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kashyap, S. R. Articles by DeFronzo, R. A. Search for Related Content PubMed PubMed Citation Articles by Kashyap, S. R. Articles by DeFronzo, R. A. Social Bookmarking                What's this?

Insulin Reduces Plasma Arginase Activity in Type 2 Diabetes Patients

Sangeeta R. Kashyap, MD^*, Abigail Lara, MD, Renliang Zhang, MD, Young Mi Park, MD and Ralph A. DeFronzo, MD^**

*Department of Endocrinology, Diabetes and Metabolism, Cleveland Clinic,
Department of Cell Biology, Lerner Institute, Cleveland Clinic,
**Diabetes Division, University of Texas Health Science Center, San Antonio

kashyas{at}ccf.org

ABSTRACT

Objective: We sought to determine whether dysregulation of arginine metabolism is related to insulin resistance and underlies impaired nitric oxide generation in type 2 diabetic (T2DM) patients.

Research Design and Methods: We measured plasma arginase activity, arginine metabolites and skeletal muscle NOS activity in 12 T2DM and 10 age/BMI matched non-diabetic subjects before and following 4 hour euglycemic hyperinsulinemic clamp with muscle biopsies. Arginine metabolites were determined by tandem mass spectroscopy. Arginase activity was determined by conversion of [¹⁴C] guanidoinoarginine to [¹⁴ C] urea.

Results: Glucose disposal (Rd) was reduced by 50% in diabetic vs. control subjects. NOS activity was 4 fold reduced in the diabetic group (107 ± 45 vs. 459 ± 100 pmol/min•mg protein, P<0.05) and failed to increase with insulin. Plasma arginase activity was increased by 50% in diabetic vs. control group (0.48 ± 0.11 vs.0.32 ± 0.12 umol/ml•hr, P < 0.05) and markedly declined in diabetic subjects with 4-h insulin infusion (to 0.13 ± 0.04 vs. basal, P <0.05). In both groups collectively, plasma arginase activity correlated positively with fasting plasma glucose (R = 0.46, P < 0.05) and HbA1c levels (R = 0.51, P < 0.02), but not with Rd.

Conclusions: Plasma arginase activity is increased in T2DM subjects with impaired NOS activity, correlates with the degree of hyperglycemia, and is reduced by physiologic hyperinsulinemia. Elevated arginase activity may contribute to impaired nitric oxide generation in type 2 diabetes and insulin may ameliorate this defect via reducing arginase activity.

CiteULike    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				E. Altmaier, S. L. Ramsay, A. Graber, H.-W. Mewes, K. M. Weinberger, and K. Suhre Bioinformatics Analysis of Targeted Metabolomics--Uncovering Old and New Tales of Diabetic Mice under Medication Endocrinology, July 1, 2008; 149(7): 3478 - 3489. [Abstract] [Full Text] [PDF]