help button home button Endocrine Society Endocrinology
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Copyright Permission
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Tajiri, Y.
Right arrow Articles by Grill, V.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Tajiri, Y.
Right arrow Articles by Grill, V.
Endocrinology Vol. 138, No. 1 273-280
Copyright © 1997 by The Endocrine Society

ARTICLES

Long Term Effects of Aminoguanidine on Insulin Release and Biosynthesis: Evidence That the Formation of Advanced Glycosylation End Products Inhibits B Cell Function1

Yuji Tajiri, Christer Möller and Valdemar Grill

Department of Molecular Medicine, Endocrine and Diabetes Unit, Karolinska Hospital, Karolinska Institute, Stockholm, Sweden; and the Department of Internal Medicine, University of Trondheim, Trondheim, Norway

Address all correspondence and requests for reprints to: Dr. Valdemar Grill, Department of Molecular Medicine, Endocrine and Diabetes Unit, Karolinska Hospital, S-17176 Stockholm, Sweden.

Chronic hyperglycemia has adverse effects on B cell function. We investigated the possible role of advanced glycosylation end products (AGEs) in glucotoxicity. Rat islets were cultured at different glucose concentrations for 1–6 weeks in RPMI 1640. Culture was performed with or without aminoguanidine (AG), which is known to prevent AGE formation in other tissues. AGE-associated fluorescence (370 nm excitation and 440 nm emission) progressively increased during 6 weeks of culture at 38 mM, but not at 11 or 5.5 mM, glucose. The increase in fluorescence was significantly inhibited by AG. The effects of AG on insulin secretion were tested directly after the culture period as well as after a wash-out period of continued culture at 11 mM glucose in the absence of AG. The presence of AG during culture for 1 week at 38 mM glucose failed to affect basal release at 3.3 mM glucose or stimulated release at 27 mM glucose. AG was ineffective whether tested directly after the culture period or after wash-out. When the same culture conditions were prolonged for 6 weeks, culture with AG suppressed basal and stimulated insulin secretion after the culture period. However, after wash-out, previous AG treatment enhanced the insulin response to 27 mM glucose 2-fold compared to culture without AG (P < 0.01). Proinsulin and total protein biosyntheses in 38 mM glucose-cultured islets were increased 40–80% by AG after 6 weeks of culture, and this effect was similar after wash-out. Preproinsulin messenger RNA levels were significantly increased (P < 0.05) after 6 weeks of culture with AG. NG-Methyl-L-arginine, a nitric oxide synthase inhibitor, failed to mimic the effects of AG. The results indicate that the time-dependent beneficial effects of AG on insulin secretion and biosynthesis are related to inhibitory effects on AGE formation and that accumulation of islet AGEs could be important for glucotoxicity toward B cells.




This article has been cited by other articles:


Home page
 EndocrinologyHome page
Z. Zhao, C. Zhao, X. H. Zhang, F. Zheng, W. Cai, H. Vlassara, and Z. A. Ma
Advanced Glycation End Products Inhibit Glucose-Stimulated Insulin Secretion through Nitric Oxide-Dependent Inhibition of Cytochrome c Oxidase and Adenosine Triphosphate Synthesis
Endocrinology, June 1, 2009; 150(6): 2569 - 2576.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
A. Cassese, I. Esposito, F. Fiory, A. P. M. Barbagallo, F. Paturzo, P. Mirra, L. Ulianich, F. Giacco, C. Iadicicco, A. Lombardi, et al.
In Skeletal Muscle Advanced Glycation End Products (AGEs) Inhibit Insulin Action and Induce the Formation of Multimolecular Complexes Including the Receptor for AGEs
J. Biol. Chem., December 26, 2008; 283(52): 36088 - 36099.
[Abstract] [Full Text] [PDF]

Home page
 FASEB J.Home page
K. Maedler, F. T. Schulthess, C. Bielman, T. Berney, C. Bonny, M. Prentki, M. Y. Donath, and R. Roduit
Glucose and leptin induce apoptosis in human {beta}-cells and impair glucose-stimulated insulin secretion through activation of c-Jun N-terminal kinases
FASEB J, June 1, 2008; 22(6): 1905 - 1913.
[Abstract] [Full Text] [PDF]

Home page
 Endocr. Rev.Home page
V. Poitout and R. P. Robertson
Glucolipotoxicity: Fuel Excess and {beta}-Cell Dysfunction
Endocr. Rev., May 1, 2008; 29(3): 351 - 366.
[Abstract] [Full Text] [PDF]

Home page
 J Mol EndocrinolHome page
S. Kooptiwut, M. Kebede, S. Zraika, S. Visinoni, K. Aston-Mourney, J. Favaloro, C. Tikellis, M. C Thomas, J. M Forbes, M. E Cooper, et al.
High glucose-induced impairment in insulin secretion is associated with reduction in islet glucokinase in a mouse model of susceptibility to islet dysfunction
J. Mol. Endocrinol., August 1, 2005; 35(1): 39 - 48.
[Abstract] [Full Text] [PDF]

Home page
 DiabetesHome page
M. Peppa, C. He, M. Hattori, R. McEvoy, F. Zheng, and H. Vlassara
Fetal or Neonatal Low-Glycotoxin Environment Prevents Autoimmune Diabetes in NOD Mice
Diabetes, June 1, 2003; 52(6): 1441 - 1448.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
I. Maestre, J. Jordan, S. Calvo, J. A. Reig, V. Cena, B. Soria, M. Prentki, and E. Roche
Mitochondrial Dysfunction Is Involved in Apoptosis Induced by Serum Withdrawal and Fatty Acids in the {beta}-Cell Line Ins-1
Endocrinology, January 1, 2003; 144(1): 335 - 345.
[Abstract] [Full Text] [PDF]

Home page
 DiabetesHome page
J. L. Evans, I. D. Goldfine, B. A. Maddux, and G. M. Grodsky
Are Oxidative Stress-Activated Signaling Pathways Mediators of Insulin Resistance and {beta}-Cell Dysfunction?
Diabetes, January 1, 2003; 52(1): 1 - 8.
[Abstract] [Full Text] [PDF]

Home page
 Endocr. Rev.Home page
J. L. Evans, I. D. Goldfine, B. A. Maddux, and G. M. Grodsky
Oxidative Stress and Stress-Activated Signaling Pathways: A Unifying Hypothesis of Type 2 Diabetes
Endocr. Rev., October 1, 2002; 23(5): 599 - 622.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
V. Poitout and R. P. Robertson
Minireview: Secondary {beta}-Cell Failure in Type 2 Diabetes--A Convergence of Glucotoxicity and Lipotoxicity
Endocrinology, February 1, 2002; 143(2): 339 - 342.
[Abstract] [Full Text] [PDF]

Home page
 DiabetesHome page
M. Biarnes, M. Montolio, V. Nacher, M. Raurell, J. Soler, and E. Montanya
{beta}-Cell Death and Mass in Syngeneically Transplanted Islets Exposed to Short- and Long-Term Hyperglycemia
Diabetes, January 1, 2002; 51(1): 66 - 72.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
Y. Tanaka, C. E. Gleason, P. O. T. Tran, J. S. Harmon, and R. P. Robertson
Prevention of glucose toxicity in HIT-T15 cells and Zucker diabetic fatty rats by antioxidants
PNAS, September 14, 1999; 96(19): 10857 - 10862.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Pathol.Home page
M. Koyama, R.-i. Wada, H. Sakuraba, H. Mizukami, and S. Yagihashi
Accelerated Loss of Islet ß Cells in Sucrose-Fed Goto-Kakizaki Rats, a Genetic Model of Non-Insulin-Dependent Diabetes Mellitus
Am. J. Pathol., August 1, 1998; 153(2): 537 - 545.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Endocrinology Endocrine Reviews J. Clin. End. & Metab.
Molecular Endocrinology Recent Prog. Horm. Res. All Endocrine Journals
Copyright © 1997 by The Endocrine Society