nach oben

Endocrine

Erschienen in:

04.08.2016 | Review

A hypothetical model to solve the controversy over the involvement of UCP2 in palmitate-induced β-cell dysfunction

verfasst von: Alaa Shaheen, Ahmad M. A. Aljebali

Erschienen in: Endocrine | Ausgabe 2/2016

Einloggen, um Zugang zu erhalten

Abstract

The aim of this article is to solve an existing controversy over the involvement of uncoupling protein-2 in the impairment of glucose-stimulated insulin secretion induced by chronic exposure of β-cells to palmitate. We analyzed and compared the results of studies that support and that deny the involvement of uncoupling protein-2 in this impairment. We observed that this impairment could occur in multiple stages. We provide a model in which palmitate-induced impairment of glucose-stimulated insulin secretion is proposed to occur in two stages, early stage and late stage, depending on the integrity of electron supply (glycolysis and Krebs cycle) and transport system through electron transport chain after palmitate treatment. Prolonged exposure of β-cells to palmitate can impair this system. Early-stage impairment occurs due to uncoupling by uncoupling protein-2 when this system is still intact. When this system becomes impaired, late-stage impairment occurs mainly due to reduced glucose-stimulated adenosine triphosphate production independent of uncoupling by uncoupling protein-2. The change in glucose-stimulated oxygen uptake after palmitate treatment reflects the integrity of this system and can be used to differentiate between the two stages. Some β-cells lines and islets appear to be more resistant to palmitate-induced impairment of electron supply and transport system than others, and therefore early stage is prominent in the more resistant cell lines and less prominent or absent in the less resistant cell lines. This may help to resolve the pathogenesis of diabetes and to monitor the progression of palmitate-induced β-cell dysfunction.

P. Newsholme, V. Cruzat, F. Arfuso, K. Keane, Nutrient regulation of insulin secretion and action. J. Endocrinol. 221(3), R105–R120 (2014). doi:10.1530/JOE-13-0616 CrossRefPubMed

G.M. Cooper. The Cell: A Molecular Approach. 2nd edn. (Sinauer Associates, Sunderland, MA, 2000)

P. Mitchell, Coupling of phosphorylation to electron and hydrogen transfer by a chemi-osmotic type of mechanism. Nature 191, 144–148 (1961). doi:10.1038/191144a0 CrossRefPubMed

N. Lameloise, P. Muzzin, M. Prentki, F. Assimacopoulos-Jeannet, Uncoupling protein-2: a possible link between fatty acid excess and impaired glucose-induced insulin secretion? Diabetes 50, 803–809 (2001). doi:10.2337/diabetes.50.4.803 CrossRefPubMed

J.W. Joseph, V. Koshkin, M.C. Saleh, W.I. Sivitz, C.Y. Zhang, B.B. Lowell et al., Free fatty acid-induced beta-cell defects are dependent on uncoupling protein-2 expression. J. Biol. Chem. 279, 51049–51056 (2004). doi:10.1074/jbc.M409189200 CrossRefPubMed

T.C. Esteves, M.D. Brand, The reactions catalysed by the mitochondrial uncoupling proteins UCP2 and UCP3. Biochim. Biophys. Acta. 1709, 35–44 (2005). doi:10.1016/j.bbabio.2005.06.002 CrossRefPubMed

K.S. Echtay, D. Roussel, J. St-Pierre, M.B. Jekabsons, S. Cadenas, J.A. Stuart et al., Superoxide activates mitochondrial uncoupling proteins. Nature. 415, 96–99 (2002). doi:10.1038/415096a CrossRefPubMed

K.S. Echtay, M.P. Murphy, R.A. Smith, D.A. Talbot, M.D. Brand, Superoxide activates mitochondrial uncoupling protein-2 from the matrix side: studies using targeted antioxidants. J. Biol. Chem. 277, 47129–47135 (2002). doi:10.1074/jbc.M208262200 CrossRefPubMed

S. Krauss, C.Y. Zhang, L. Scorrano, L.T. Dalgaard, J. St-Pierre, S.T. Grey et al., Superoxide-mediated activation of uncoupling protein-2 causes pancreatic beta cell dysfunction. J. Clin. Invest. 112, 1831–1842 (2003). doi:10.1172/JCI19774 CrossRefPubMedPubMedCentral

10.

C. Carlsson, L.A. Borg, N. Welsh, Sodium palmitate induces partial mitochondrial uncoupling and reactive oxygen species in rat pancreatic islets in vitro. Endocrinology. 140, 3422–3428 (1999). doi:10.1210/en.140.8.3422 PubMed

11.

J.W. Joseph, V. Koshkin, C.Y. Zhang, J. Wang, B.B. Lowell, C.B. Chan et al., Uncoupling protein-2 knockout mice have enhanced insulin secretory capacity after a high-fat diet. Diabetes. 51, 3211–3219 (2002). doi:10.2337/diabetes.51.11.3211 CrossRefPubMed

12.

V. Hirschberg Jensen, C. Affourtit, Mitochondrial uncoupling protein-2 is not involved in palmitate-induced impairment of glucose-stimulated insulin secretion in INS-1E insulinoma cells and is not needed for the amplification of insulin release. Biochem. Biophys. Rep. 1, 8–15 (2015). doi:10.1016/j.bbrep.2015.03.008 PubMedPubMedCentral

13.

Alberts B, Johnson A, Lewis J, Raff M, Roberts K, Walter P. Electron-Transport Chains and their Proton Pumps in Molecular Biology of the Cell, 4th edn. (Garland Science, New York, 2002).

14.

J. Barlow, V.H. Jensen, M. Jastroch, C. Affourtit, Palmitate-induced impairment of glucose-stimulated insulin secretion precedes mitochondrial dysfunction in mouse pancreatic islets. Biochem. J. 473(4), 487–496 (2016). doi:10.1042/BJ20151080 CrossRefPubMed

15.

J. Pi, S. Collins, Reactive oxygen species and uncoupling protein-2 in pancreatic β-cell function. Diabetes Obes. Metab. 12(Suppl. 2), 141–148 (2010). doi:10.1111/j.1463-1326.2010.01269.x CrossRefPubMed

16.

J. Barlow, V. Hirschberg-Jensen, C. Affourtit, Uncoupling protein-2 attenuates palmitoleate protection against the cytotoxic production of mitochondrial reactive oxygen species in INS-1E insulinoma cells. Redox Biol. 4, 14–22 (2015). doi:10.1016/j.redox.2014.11.009 CrossRefPubMed

17.

A.F. Oliveira, D.A. Cunha, L. Ladriere, M. Igoillo-Esteve, M. Bugliani, P. Marchetti, M. Cnop, In vitro use of free fatty acids bound to albumin: a comparison of protocols. Biotechniques 58(5), 228–233 (2015). doi:10.2144/000114285 CrossRefPubMed

18.

A.K. Busch, D. Cordery, G.S. Denyer, T.J. Biden, Expression profiling of palmitate- and oleate-regulated genes provides novel insights into the effects of chronic lipid exposure on pancreatic β-cell function. Diabetes 51, 977–987 (2002). doi:10.2337/diabetes.51.4.977 CrossRefPubMed

19.

H. Yoshikawa, Y. Tajiri, Y. Sako, T. Hashimoto, F. Umeda, H. Nawata, Effects of free fatty acids on beta-cell functions: a possible involvement of peroxisome proliferator-activated receptors alpha or pancreatic/duodenal homeobox. Metabolism 50, 613–618 (2001). doi:10.1053/meta.2001.22565 CrossRefPubMed

20.

T.C. Brelje, N.V. Bhagroo, L.E. Stout, R.L. Sorenson, Beneficial effects of lipids and prolactin on insulin secretion and beta-cell proliferation: a role for lipids in the adaptation of islets to pregnancy. J. Endocrinol. 197, 265–276 (2008). doi:10.1677/JOE-07-0657 CrossRefPubMed

21.

Y. Terauchi, H. Sakura, K. Yasuda, K. Iwamoto, N. Takahashi, K. Ito et al., Pancreatic beta-cell-specific targeted disruption of glucokinase gene: diabetes mellitus due to defective insulin secretion to glucose. J. Biol. Chem. 270, 30253–30256 (1995). doi:10.1074/jbc.270.51.30253 CrossRefPubMed

22.

J. Xiao, S. Gregersen, M. Kruhøffer, S.B. Pedersen, T.F. Ørntoft, K. Hermansen, The effect of chronic exposure to fatty acids on gene expression in clonal insulin-producing cells: studies using high density oligonucleotide microarray. Endocrinology 142, 4777–4784 (2001). doi:10.1210/en.142.11.4777 CrossRefPubMed

23.

M. Kebede, J. Favaloro, J.E. Gunton, D.R. Laybutt, M. Shaw, N. Wong et al., Fructose-1,6-bisphosphatase overexpression in pancreatic β-cells results in reduced insulin secretion: a new mechanism for fat-induced impairment of β-cell function. Diabetes 57, 1887–1895 (2008). doi:10.2337/db07-1326 CrossRefPubMedPubMedCentral

24.

Y. Zhang, Z. Xie, G. Zhou, H. Zhang, J. Lu, W.J. Zhang, Fructose-1,6-bisphosphatase regulates glucose-stimulated insulin secretion of mouse pancreatic beta-cells. Endocrinology 151, 4688–4695 (2010). doi:10.1210/en.2009-1185 CrossRefPubMed

25.

E. Hall, P. Volkov, T. Dayeh, K. Bacos, T. Rönn, M.D. Nitert et al., Effects of palmitate on genome-wide mRNA expression and DNA methylation patterns in human pancreatic islets. BMC Med. 12, 103 (2014). doi:10.1186/1741-7015-12-103 CrossRefPubMedPubMedCentral

26.

N. Sekine, V. Cirulli, R. Regazzi, L.J. Brown, E. Gine, J. Tamarit-Rodriguez et al., Low lactate dehydrogenase and high mitochondrial glycerol phosphate dehydrogenase in pancreatic beta-cells: potential role in nutrient sensing. J. Biol. Chem. 269, 4895–4902 (1994)PubMed

27.

C. Zhao, G.A. Rutter, Overexpression of lactate dehydrogenase A attenuates glucose-induced insulin secretion in stable MIN-6 β-cell lines. FEBS Lett. 430, 213–216 (1998). doi:10.1016/S0014-5793(98)00600-0 CrossRefPubMed

28.

E.K. Ainscow, C. Zhao, G.A. Rutter, Acute overexpression of lactate dehydrogenase-A perturbs beta-cell mitochondrial metabolism and insulin secretion. Diabetes 49, 1149–1155 (2000). doi:10.2337/diabetes.49.7.1149 CrossRefPubMed

29.

Y.P. Zhou, V.E. Grill, Palmitate-induced beta-cell insensitivity to glucose is coupled to decreased pyruvate dehydrogenase activity and enhanced kinase activity in rat pancreatic islets. Diabetes 44, 394–399 (1995). doi:10.2337/diab.44.4.394 CrossRefPubMed

30.

J. Xu, J. Han, P.N. Epstein, Y.Q. Liu, Regulation of PDK mRNA by high fatty acid and glucose in pancreatic islets. Biochem. Biophys. Res. Commun. 344, 827–833 (2006). doi:10.1016/j.bbrc.2006.03.211 CrossRefPubMed

31.

M. Cnop, B. Abdulkarim, G. Bottu, D.A. Cunha, M. Igoillo-Esteve, M. Masini et al., RNA sequencing identifies dysregulation of the human pancreatic islet transcriptome by the saturated fatty acid palmitate. Diabetes 63, 1978–1993 (2014). doi:10.2337/db13-1383 CrossRefPubMed

32.

T. Koeck, A.H. Olsson, M.D. Nitert, V.V. Sharoyko, C. Ladenvall, O. Kotova et al., A common variant in TFB1M is associated with reduced insulin secretion and increased future risk of type 2 diabetes. Cell Metab. 13, 80–91 (2011). doi:10.1016/j.cmet.2010.12.007 CrossRefPubMed

33.

J.A. Stuart, M.F. Brown, Mitochondrial DNA maintenance and bioenergetics. Biochim. Biophys. Acta. 1757, 79–89 (2006). doi:10.1016/j.bbabio.2006.01.003 CrossRefPubMed

34.

S.U. Mir, N.M. George, L. Zahoor, R. Harms, Z. Guinn, N.E. Sarvetnick, Inhibition of autophagic turnover in β-cells by fatty acids and glucose leads to apoptotic cell death. J. Biol. Chem. 290, 6071–6085 (2015). doi:10.1074/jbc.M114.605345 CrossRefPubMed

Titel: A hypothetical model to solve the controversy over the involvement of UCP2 in palmitate-induced β-cell dysfunction
verfasst von: Alaa Shaheen
Ahmad M. A. Aljebali
Publikationsdatum: 04.08.2016
Verlag: Springer US
Erschienen in: Endocrine / Ausgabe 2/2016
Print ISSN: 1355-008X
Elektronische ISSN: 1559-0100
DOI: https://doi.org/10.1007/s12020-016-1051-1

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

^{Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag}

Kostenlos registrieren

Neu im Fachgebiet Innere Medizin

Notfall-TEP der Hüfte ist auch bei 90-Jährigen machbar

26.04.2024 Hüft-TEP Nachrichten

Ob bei einer Notfalloperation nach Schenkelhalsfraktur eine Hemiarthroplastik oder eine totale Endoprothese (TEP) eingebaut wird, sollte nicht allein vom Alter der Patientinnen und Patienten abhängen. Auch über 90-Jährige können von der TEP profitieren.

Niedriger diastolischer Blutdruck erhöht Risiko für schwere kardiovaskuläre Komplikationen

25.04.2024 Hypotonie Nachrichten

Wenn unter einer medikamentösen Hochdrucktherapie der diastolische Blutdruck in den Keller geht, steigt das Risiko für schwere kardiovaskuläre Ereignisse: Darauf deutet eine Sekundäranalyse der SPRINT-Studie hin.

Bei schweren Reaktionen auf Insektenstiche empfiehlt sich eine spezifische Immuntherapie

25.04.2024 Allergien und Intoleranzreaktionen Nachrichten

Insektenstiche sind bei Erwachsenen die häufigsten Auslöser einer Anaphylaxie. Einen wirksamen Schutz vor schweren anaphylaktischen Reaktionen bietet die allergenspezifische Immuntherapie. Jedoch kommt sie noch viel zu selten zum Einsatz.

Therapiestart mit Blutdrucksenkern erhöht Frakturrisiko

25.04.2024 Hypertonie Nachrichten

Beginnen ältere Männer im Pflegeheim eine Antihypertensiva-Therapie, dann ist die Frakturrate in den folgenden 30 Tagen mehr als verdoppelt. Besonders häufig stürzen Demenzkranke und Männer, die erstmals Blutdrucksenker nehmen. Dafür spricht eine Analyse unter US-Veteranen.

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Springer Medizin

Abstract

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 2/2016

Two-miRNA classifiers differentiate mutation-negative follicular thyroid carcinomas and follicular thyroid adenomas in fine needle aspirations with high specificity

Physical exam in asymptomatic people drivers the detection of thyroid nodules undergoing ultrasound guided fine needle aspiration biopsy

Assessment of trabecular bone score (TBS) in overweight/obese men: effect of metabolic and anthropometric factors

Brown adipose tissue localization using 18F-FDG PET/MRI in adult

Implications of exercise-induced adipo-myokines in bone metabolism