Diabetes
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Purchase Article
Right arrow View Shopping Cart
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
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 Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Maedler, K.
Right arrow Articles by Donath, M. Y.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Maedler, K.
Right arrow Articles by Donath, M. Y.
Social Bookmarking
Add to CiteULike   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?
Diabetes 50:69-76, 2001
© 2001 by the American Diabetes Association, Inc.

Distinct Effects of Saturated and Monounsaturated Fatty Acids on ß-Cell Turnover and Function

K. Maedler, G.A. Spinas, D. Dyntar, W. Moritz, N. Kaiser, and Marc Y. Donath

From the Division of Endocrinology and Diabetes (K.M., G.A.S., D.D., W.M., M.Y.D.), University Hospital, Zurich, Switzerland; and the Department of Endocrinology and Metabolism (N.K.), Hebrew University—Hadassah Medical Center, Jerusalem, Israel.

Address correspondence and reprint requests to Marc Donath, MD, Division of Endocrinology and Diabetes, Department of Medicine, University Hospital, CH-8091 Zurich, Switzerland. E-mail: marc.donath{at}dim.usz.ch .

Glucotoxicity and lipotoxicity contribute to the impaired ß-cell function observed in type 2 diabetes. Here we examine the effect of saturated and unsaturated fatty acids at different glucose concentrations on ß-cell proliferation and apoptosis. Adult rat pancreatic islets were cultured onto plates coated with extracellular matrix derived from bovine corneal endothelial cells. Exposure of islets to saturated fatty acid (0.5 mmol/l palmitic acid) in medium containing 5.5, 11.1, or 33.3 mmol/l glucose for 4 days resulted in a five- to ninefold increase of ß-cell DNA fragmentation. In contrast, monounsaturated palmitoleic acid alone (0.5 mmol/l) or in combination with palmitic acid (0.25 or 0.5 mmol/l each) did not affect DNA fragmentation. Increasing concentrations of glucose promoted ß-cell proliferation that was dramatically reduced by palmitic acid. Palmitoleic acid enhanced the proliferation activity in medium containing 5.5 mmol/l glucose but had no additional effect at higher glucose concentrations (11.1 and 33.3 mmol/l). The cell-permeable ceramide analog C2-ceramide mimicked both the palmitic acid—induced ß-cell apoptosis and decrease in proliferation. Moreover, the ceramide synthetase inhibitor fumonisin B1 blocked the deleterious effects of palmitic acid on ß-cell viability. Additionally, palmitic acid but not palmitoleic acid decreased the expression of the mitochondrial adenine nucleotide translocator and induced release of cytochrome c from the mitochondria into the cytosol. Finally, palmitoleic acid improved ß-cell—secretory function that was reduced by palmitic acid. Taken together, these results suggest that the lipotoxic effect of the saturated palmitic acid involves an increased apoptosis rate coupled with reduced proliferation capacity of ß-cells and impaired insulin secretion. The deleterious effect of palmitate on ß-cell turnover is mediated via formation of ceramide and activation of the apoptotic mitochondrial pathway. In contrast, the monounsaturated palmitoleic acid does not affect ß-cell apoptosis, yet it promotes ß-cell proliferation at low glucose concentrations, counteracting the negative effects of palmitic acid as well as improving ß-cell function.


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


This article has been cited by other articles:


Home page
 DiabetesHome page
S. C. Martinez, K. Tanabe, C. Cras-Meneur, N. A. Abumrad, E. Bernal-Mizrachi, and M. A. Permutt
Inhibition of Foxo1 Protects Pancreatic Islet {beta}-Cells Against Fatty Acid and Endoplasmic Reticulum Stress-Induced Apoptosis
Diabetes, April 1, 2008; 57(4): 846 - 859.
[Abstract] [Full Text] [PDF]

Home page
 DiabetesHome page
C. S. Olofsson, S. Collins, M. Bengtsson, L. Eliasson, A. Salehi, K. Shimomura, A. Tarasov, C. Holm, F. Ashcroft, and P. Rorsman
Long-Term Exposure to Glucose and Lipids Inhibits Glucose-Induced Insulin Secretion Downstream of Granule Fusion With Plasma Membrane
Diabetes, July 1, 2007; 56(7): 1888 - 1897.
[Abstract] [Full Text] [PDF]

Home page
 J Mol EndocrinolHome page
Y. Zhang, M. Xu, S. Zhang, L. Yan, C. Yang, W. Lu, Y. Li, and H. Cheng
The role of G protein-coupled receptor 40 in lipoapoptosis in mouse {beta}-cell line NIT-1
J. Mol. Endocrinol., June 1, 2007; 38(6): 651 - 661.
[Abstract] [Full Text] [PDF]

Home page
 DiabetesHome page
S. S. Choe, A H. Choi, J.-W. Lee, K. H. Kim, J.-J. Chung, J. Park, K.-M. Lee, K.-G. Park, I.-K. Lee, and J. B. Kim
Chronic Activation of Liver X Receptor Induces {beta}-Cell Apoptosis Through Hyperactivation of Lipogenesis: Liver X Receptor-Mediated Lipotoxicity in Pancreatic {beta}-Cells
Diabetes, June 1, 2007; 56(6): 1534 - 1543.
[Abstract] [Full Text] [PDF]

Home page
 DiabetesHome page
J. B. Flowers, M. E. Rabaglia, K. L. Schueler, M. T. Flowers, H. Lan, M. P. Keller, J. M. Ntambi, and A. D. Attie
Loss of Stearoyl-CoA Desaturase-1 Improves Insulin Sensitivity in Lean Mice but Worsens Diabetes in Leptin-Deficient Obese Mice
Diabetes, May 1, 2007; 56(5): 1228 - 1239.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Endocrinol. Metab.Home page
S. M. Turpin, G. I. Lancaster, I. Darby, M. A. Febbraio, and M. J. Watt
Apoptosis in skeletal muscle myotubes is induced by ceramides and is positively related to insulin resistance
Am J Physiol Endocrinol Metab, December 1, 2006; 291(6): E1341 - E1350.
[Abstract] [Full Text] [PDF]

Home page
 DiabetesHome page
K. Maedler, D. M. Schumann, N. Sauter, H. Ellingsgaard, D. Bosco, R. Baertschiger, Y. Iwakura, J. Oberholzer, C. B. Wollheim, B. R. Gauthier, et al.
Low Concentration of Interleukin-1{beta} Induces FLICE-Inhibitory Protein-Mediated {beta}-Cell Proliferation in Human Pancreatic Islets.
Diabetes, October 1, 2006; 55(10): 2713 - 2722.
[Abstract] [Full Text] [PDF]

Home page
 DiabetesHome page
K. Maedler, D. M. Schumann, F. Schulthess, J. Oberholzer, D. Bosco, T. Berney, and M. Y. Donath
Aging Correlates With Decreased {beta}-Cell Proliferative Capacity and Enhanced Sensitivity to Apoptosis: A Potential Role for Fas and Pancreatic Duodenal Homeobox-1
Diabetes, September 1, 2006; 55(9): 2455 - 2462.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Endocrinol. Metab.Home page
Y. Wei, D. Wang, F. Topczewski, and M. J. Pagliassotti
Saturated fatty acids induce endoplasmic reticulum stress and apoptosis independently of ceramide in liver cells
Am J Physiol Endocrinol Metab, August 1, 2006; 291(2): E275 - E281.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
E. Karaskov, C. Scott, L. Zhang, T. Teodoro, M. Ravazzola, and A. Volchuk
Chronic Palmitate But Not Oleate Exposure Induces Endoplasmic Reticulum Stress, Which May Contribute to INS-1 Pancreatic {beta}-Cell Apoptosis
Endocrinology, July 1, 2006; 147(7): 3398 - 3407.
[Abstract] [Full Text] [PDF]

Home page
 J Mol EndocrinolHome page
K. Ravnskjaer, M. Boergesen, L. T Dalgaard, and S. Mandrup
Glucose-induced repression of PPAR{alpha} gene expression in pancreatic {beta}-cells involves PP2A activation and AMPK inactivation.
J. Mol. Endocrinol., April 1, 2006; 36(2): 289 - 299.
[Abstract] [Full Text] [PDF]

Home page
 DiabetesHome page
L. I. Rachek, N. P. Thornley, V. I. Grishko, S. P. LeDoux, and G. L. Wilson
Protection of INS-1 Cells From Free Fatty Acid-Induced Apoptosis by Targeting hOGG1 to Mitochondria.
Diabetes, April 1, 2006; 55(4): 1022 - 1028.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Endocrinol. Metab.Home page
J. Hong, L. Chen, P. B. Jeppesen, I. Nordentoft, and K. Hermansen
Stevioside counteracts the {alpha}-cell hypersecretion caused by long-term palmitate exposure
Am J Physiol Endocrinol Metab, March 1, 2006; 290(3): E416 - E422.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
D. Wang, Y. Wei, and M. J. Pagliassotti
Saturated Fatty Acids Promote Endoplasmic Reticulum Stress and Liver Injury in Rats with Hepatic Steatosis
Endocrinology, February 1, 2006; 147(2): 943 - 951.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
K. Staiger, N. Stefan, H. Staiger, M. D. Brendel, D. Brandhorst, R. G. Bretzel, F. Machicao, M. Kellerer, M. Stumvoll, A. Fritsche, et al.
Adiponectin Is Functionally Active in Human Islets but Does Not Affect Insulin Secretory Function or {beta}-Cell Lipoapoptosis
J. Clin. Endocrinol. Metab., December 1, 2005; 90(12): 6707 - 6713.
[Abstract] [Full Text] [PDF]

Home page
 DiabetesHome page
M. Y. Donath, J. A. Ehses, K. Maedler, D. M. Schumann, H. Ellingsgaard, E. Eppler, and M. Reinecke
Mechanisms of {beta}-Cell Death in Type 2 Diabetes
Diabetes, December 1, 2005; 54(suppl_2): S108 - S113.
[Abstract] [Full Text] [PDF]

Home page
 ReproductionHome page
J L M R Leroy, T Vanholder, B Mateusen, A Christophe, G Opsomer, A de Kruif, G Genicot, and A Van Soom
Non-esterified fatty acids in follicular fluid of dairy cows and their effect on developmental capacity of bovine oocytes in vitro
Reproduction, October 1, 2005; 130(4): 485 - 495.
[Abstract] [Full Text] [PDF]

Home page
 DiabetesHome page
A. K. Busch, E. Gurisik, D. V. Cordery, M. Sudlow, G. S. Denyer, D. R. Laybutt, W. E. Hughes, and T. J. Biden
Increased Fatty Acid Desaturation and Enhanced Expression of Stearoyl Coenzyme A Desaturase Protects Pancreatic {beta}-Cells from Lipoapoptosis
Diabetes, October 1, 2005; 54(10): 2917 - 2924.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
K. Ravnskjaer, M. Boergesen, B. Rubi, J. K. Larsen, T. Nielsen, J. Fridriksson, P. Maechler, and S. Mandrup
Peroxisome Proliferator-Activated Receptor {alpha} (PPAR{alpha}) Potentiates, whereas PPAR{gamma} Attenuates, Glucose-Stimulated Insulin Secretion in Pancreatic {beta}-Cells
Endocrinology, August 1, 2005; 146(8): 3266 - 3276.
[Abstract] [Full Text] [PDF]

Home page
 DiabetesHome page
Z. Medarova, S. Bonner-Weir, M. Lipes, and A. Moore
Imaging {beta}-Cell Death With a Near-Infrared Probe
Diabetes, June 1, 2005; 54(6): 1780 - 1788.
[Abstract] [Full Text] [PDF]

Home page
 DiabetesHome page
J. M. Cacicedo, S. Benjachareowong, E. Chou, N. B. Ruderman, and Y. Ido
Palmitate-Induced Apoptosis in Cultured Bovine Retinal Pericytes: Roles of NAD(P)H Oxidase, Oxidant Stress, and Ceramide
Diabetes, June 1, 2005; 54(6): 1838 - 1845.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
I. Kharroubi, L. Ladriere, A. K. Cardozo, Z. Dogusan, M. Cnop, and D. L. Eizirik
Free Fatty Acids and Cytokines Induce Pancreatic {beta}-Cell Apoptosis by Different Mechanisms: Role of Nuclear Factor-{kappa}B and Endoplasmic Reticulum Stress
Endocrinology, November 1, 2004; 145(11): 5087 - 5096.
[Abstract] [Full Text] [PDF]

Home page
 DiabetesHome page
P. C. Moore, M. A. Ugas, D. K. Hagman, S. D. Parazzoli, and V. Poitout
Evidence Against the Involvement of Oxidative Stress in Fatty Acid Inhibition of Insulin Secretion
Diabetes, October 1, 2004; 53(10): 2610 - 2616.
[Abstract] [Full Text] [PDF]

Home page
 DiabetesHome page
M.-L. Peyot, C. J. Nolan, K. Soni, E. Joly, R. Lussier, B. E. Corkey, S. P. Wang, G. A. Mitchell, and M. Prentki
Hormone-Sensitive Lipase Has a Role in Lipid Signaling for Insulin Secretion but Is Nonessential for the Incretin Action of Glucagon-Like Peptide 1
Diabetes, July 1, 2004; 53(7): 1733 - 1742.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
K. Maedler, P. Sergeev, J. A. Ehses, Z. Mathe, D. Bosco, T. Berney, J.-M. Dayer, M. Reinecke, P. A. Halban, and M. Y. Donath
Leptin modulates {beta} cell expression of IL-1 receptor antagonist and release of IL-1{beta} in human islets
PNAS, May 25, 2004; 101(21): 8138 - 8143.
[Abstract] [Full Text] [PDF]

Home page
 DiabetesHome page
R. P. Robertson, J. Harmon, P. O. T. Tran, and V. Poitout
{beta}-Cell Glucose Toxicity, Lipotoxicity, and Chronic Oxidative Stress in Type 2 Diabetes
Diabetes, February 1, 2004; 53(90001): S119 - 124.
[Abstract] [Full Text]

Home page
 DiabetesHome page
T. J. Biden, D. Robinson, D. Cordery, W. E. Hughes, and A. K. Busch
Chronic Effects of Fatty Acids on Pancreatic {beta}-Cell Function: New Insights From Functional Genomics
Diabetes, February 1, 2004; 53(90001): S159 - 165.
[Abstract] [Full Text]

Home page
 EndocrinologyHome page
W. El-Assaad, J. Buteau, M.-L. Peyot, C. Nolan, R. Roduit, S. Hardy, E. Joly, G. Dbaibo, L. Rosenberg, and M. Prentki
Saturated Fatty Acids Synergize with Elevated Glucose to Cause Pancreatic {beta}-Cell Death
Endocrinology, September 1, 2003; 144(9): 4154 - 4163.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
C. L. Kelpe, P. C. Moore, S. D. Parazzoli, B. Wicksteed, C. J. Rhodes, and V. Poitout
Palmitate Inhibition of Insulin Gene Expression Is Mediated at the Transcriptional Level via Ceramide Synthesis
J. Biol. Chem., August 8, 2003; 278(32): 30015 - 30021.
[Abstract] [Full Text] [PDF]

Home page
 DiabetesHome page
K. Eitel, H. Staiger, J. Rieger, H. Mischak, H. Brandhorst, M. D. Brendel, R. G. Bretzel, H.-U. Haring, and M. Kellerer
Protein Kinase C {delta} Activation and Translocation to the Nucleus Are Required for Fatty Acid-Induced Apoptosis of Insulin-Secreting Cells
Diabetes, April 1, 2003; 52(4): 991 - 997.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
L. L. Listenberger, X. Han, S. E. Lewis, S. Cases, R. V. Farese Jr., D. S. Ory, and J. E. Schaffer
Triglyceride accumulation protects against fatty acid-induced lipotoxicity
PNAS, March 18, 2003; 100(6): 3077 - 3082.
[Abstract] [Full Text] [PDF]

Home page
 DiabetesHome page
K. Maedler, J. Oberholzer, P. Bucher, G. A. Spinas, and M. Y. Donath
Monounsaturated Fatty Acids Prevent the Deleterious Effects of Palmitate and High Glucose on Human Pancreatic {beta}-Cell Turnover and Function
Diabetes, March 1, 2003; 52(3): 726 - 733.
[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
 Proc. Natl. Acad. Sci. USAHome page
K. Maedler, A. Fontana, F. Ris, P. Sergeev, C. Toso, J. Oberholzer, R. Lehmann, F. Bachmann, A. Tasinato, G. A. Spinas, et al.
FLIP switches Fas-mediated glucose signaling in human pancreatic beta cells from apoptosis to cell replication
PNAS, June 11, 2002; 99(12): 8236 - 8241.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
D. R. Laybutt, A. Sharma, D. C. Sgroi, J. Gaudet, S. Bonner-Weir, and G. C. Weir
Genetic Regulation of Metabolic Pathways in beta -Cells Disrupted by Hyperglycemia
J. Biol. Chem., March 22, 2002; 277(13): 10912 - 10921.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Regul. Integr. Comp. Physiol.Home page
K. L. Regnauld, E. Leteurtre, S. J. Gutkind, C. P. Gespach, and S. Emami
Activation of adenylyl cyclases, regulation of insulin status, and cell survival by Galpha olf in pancreatic beta -cells
Am J Physiol Regulatory Integrative Comp Physiol, March 1, 2002; 282(3): R870 - R880.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
H. Wobser, H. Du{beta}mann, D. Kogel, H. Wang, C. Reimertz, C. B. Wollheim, M. M. Byrne, and J. H. M. Prehn
Dominant-negative Suppression of HNF-1alpha Results in Mitochondrial Dysfunction, INS-1 Cell Apoptosis, and Increased Sensitivity to Ceramide-, but Not to High Glucose-induced Cell Death
J. Biol. Chem., February 15, 2002; 277(8): 6413 - 6421.
[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
K. Maedler, G. A. Spinas, R. Lehmann, P. Sergeev, M. Weber, A. Fontana, N. Kaiser, and M. Y. Donath
Glucose Induces {beta}-Cell Apoptosis Via Upregulation of the Fas Receptor in Human Islets
Diabetes, August 1, 2001; 50(8): 1683 - 1690.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Diabetes Diabetes Care Clinical Diabetes Diabetes Spectrum
Copyright © 2001 by the American Diabetes Association.