Preserving insulin secretion in diabetes by inhibiting VDAC1 overexpression and surface translocation in β cells
Open accessAbstract
Type 2 diabetes (T2D) develops after years of prediabetes during which high glucose (glucotoxicity) impairs insulin secretion. We report that the ATP-conducting mitochondrial outer membrane voltage-dependent anion channel-1 (VDAC1) is upregulated in islets from T2D and non-diabetic organ donors under glucotoxic conditions. This is caused by a glucotoxicity-induced transcriptional program, triggered during years of prediabetes with suboptimal blood glucose control. Metformin counteracts VDAC1 induction. VDAC1 overexpression causes its mistargeting to the plasma membrane of the insulin-secreting β cells with loss of the crucial metabolic coupling factor ATP. VDAC1 antibodies and inhibitors prevent ATP loss. Through direct inhibition of VDAC1 conductance, metformin, like specific VDAC1 inhibitors and antibodies, restores the impaired generation of ATP and glucose-stimulated insulin secretion in T2D islets. Treatment of db/db mice with VDAC1 inhibitor prevents hyperglycemia, and maintains normal glucose tolerance and physiological regulation of insulin secretion. Thus, β cell function is preserved by targeting the novel diabetes executer protein VDAC1.
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Glucotoxicity decreases mitochondrial oxygen consumption rate in pancreatic β cells by inducing upregulation of voltage-dependent anion channel-1.
“The detrimental effect of hyperglycaemic glucotoxicity on mitochondria has also been recently described in pancreatic β cells with glucotoxicity decreasing mitochondrial oxygen consumption rate by inducing the upregulation of voltage-dependent anion channel-1 (Zhang et al., 2019).”
From Mitochondrial (Dys)function and Insulin Resistance: From Pathophysiological Molecular Mechanisms to the Impact of Diet (2019) · cites this paper as Zhang et al., 2019
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Cites
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BackgroundMitochondrial Matrix Calcium Is an Activating Signal for Hormone Secretion
Wiederkehr, A., Szanda, G., Akhmedov, D., Mataki, C., Heizmann, C. W., Schoonjans, K., Pozzan, T., Spät, A., & Wollheim, C. B. (2011) · Cell Metabolism · doi:10.1016/j.cmet.2011.03.015 · Cited by 149 · cited 1× · see citing works
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BackgroundVoltage-Dependent Anion Channel 1 As an Emerging Drug Target for Novel Anti-Cancer Therapeutics
Shoshan‐Barmatz, V., Krelin, Y., Shteinfer‐Kuzmine, A., & Arif, T. (2017) · Frontiers in Oncology · doi:10.3389/fonc.2017.00154 · Cited by 134 · cited 2× · see citing works
“VDAC1 is a target in cancer therapy (Shoshan-Barmatz et al., 2017) and”
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Buettner, R., Papoutsoglou, G., Scemes, E., Spray, D. C., & Dermietzel, R. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.97.7.3201 · Cited by 131 · cited 2× · see citing works
“Plasma membrane resident VDAC1 has been documented in various mouse and human tissues with the mitochondrial surface residues facing the extracellular space (Akanda et al., 2008; Buettner et al., 2000; De Pinto et al., 2010; Okada et al., 2004; Stadtmuller et al., 1999; Thinnes, 2015).”
BackgroundVDAC2-specific cellular functions and the underlying structure
Naghdi, S., & Hajnóczky, G. (2016) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2016.04.020 · Cited by 117 · cited 2× · see citing works
“VDAC1 and VDAC2 determine cell life and death by regulating flux of metabolites, nucleotides, including ADP and ATP, as well as ions between the mitochondria and the cytosol, while the VDAC3 isoform is less well characterized (Naghdi and Hajnoczky, 2016; Shoshan-Barmatz et al., 2010).”
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“In T2D islets, mitochondrial dysfunction underlies the blunted GSIS (Anello et al., 2005; Doliba et al., 2012).”
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“This is, however, difficult due to the reduced fertility of Vdac1-KO mice (Raghavan et al., 2012).”
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“T2D islets display increased transcripts of both ChREBP and TXNIP (Figure 3A), confirming published results (Bompada et al., 2016; Poungvarin et al., 2012; Shalev, 2014).”
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Ribé, E. M., & Lovestone, S. (2016) · Journal of Internal Medicine · doi:10.1111/joim.12534 · Cited by 84 · cited 1× · see citing works
“There is a striking comorbidity between T2D andAlzheimer’s disease (AD) (Ribe and Lovestone, 2016).”
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“To further characterize the roles of ChREBP and TXNIP in VDAC expression, we used INS-1 cells with Ep300 knockout (KO) established by CRISPR/ Cas9 (Bompada et al., 2016).”
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“Ce amyloid b (Ab) peptide-induced neurotoxicity (Akanda et al., 2008; Smilansky et al., 2015).”
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“Epigenetic mechanisms have been implemented in the development of b cell dysfunction in T2D through environmental stress (Nilsson and Ling, 2017).”
BackgroundVDAC: old protein with new roles in diabetes
Sasaki, K., Donthamsetty, R., Heldak, M., Cho, Y.-E., Scott, B. T., & Makino, A. (2012) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00087.2012 · Cited by 62 · cited 2× · see citing works
“, 2014) (Figure S7K), which may reflect involvement of altered VDAC1 expression in insulin target tissues (Li et al., 2016; Sasaki et al., 2012).”
BackgroundMetformin-induced anticancer activities: recent insights
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“the chemopreventive action of metformin (Safe et al., 2018) may in part be exerted through the here reported VDAC1 inhibition.”
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“Similar results were previously reportedwithmetformin in human islets under glucotoxic conditions (Masini et al., 2014) and the drug improved the function of T2D islets (Marchetti et al.”
BackgroundMethodResultInfluentialNew Insight Into Metformin Action: Regulation of ChREBP and FOXO1 Activities in Endothelial Cells
Li, X., Kover, K. L., Heruth, D. P., Watkins, D. J., Moore, W. V., Jackson, K., Zang, M., Clements, M. A., & Yan, Y. (2015) · Molecular Endocrinology · doi:10.1210/me.2015-1090 · Cited by 51 · cited 2× · see citing works
“, 2014), which prevents ChREBP nuclear translocation and TXNIP transcriptional activation (Li et al., 2015; Shaked et al., 2011; Shalev, 2014).”
BackgroundVDAC1 cysteine residues: topology and function in channel activity and apoptosis
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“, 2016), although they are not important for VDAC1-induced apoptosis (Aram et al., 2010).”
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“VDAC1 Surface Expression Involves Its Two Cysteine Residues Cell surface mistargeting of VDAC1 in T2D may involve posttranslational modification of its two cysteine residues (cys127/ 232) (Aram et al., 2010; Piroli et al., 2016), although they are not important for VDAC1-induced apoptosis (Aram et al.”
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“In AD, VDAC1 is induced early in the disease, associated with its overexpression in the neurolemma (Fernandez-Echevarria et al., 2014).”
BackgroundPalanisamy, S., Yien, E. L. H., Shi, L., Yi, L., Qi, S. H., Soon, L., Lun, T. W., & Chen, Y. N. (2018) · Pharmacy · doi:10.3390/pharmacy6030057 · Cited by 37 · cited 1× · see citing works
“Among these, glucagon-like peptide-1 (GLP-1) analogs and dipeptidyl peptidase-4 inhibitors enhance insulin secretion, while sodium-glucose cotransporter-2 inhibitors lower blood glucose by preventing renal glucose reabsorption (Palanisamy et al., 2018).”
BackgroundImaging Changes in the Cytosolic ATP-to-ADP Ratio
Tantama, M., & Yellen, G. (2014) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/b978-0-12-801415-8.00017-5 · Cited by 29 · see citing works
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“To further characterize the roles of ChREBP and TXNIP in VDAC expression, we used INS-1 cells with Ep300 knockout (KO) established by CRISPR/ Cas9 (Bompada et al., 2016).”
BackgroundMethodResultInfluentialRetnakaran, R. R., Choi, H., Ye, C., Kramer, C. K., & Zinman, B. (2018) · Diabetes Obesity and Metabolism · doi:10.1111/dom.13236 · Cited by 21 · cited 1× · see citing works
“The b cell protective action of metformin with ameliorated insulin secretion rather than improved insulin effectiveness was recently reported in T2D subjects (Retnakaran et al., 2018).”
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“Metformin Inhibits VDAC1 Solute Conductance Altered membrane permeability is further substantiated by patch-clamp experiments (Buda et al., 2013).”
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“Extramitochondrial plasma membrane VDAC1 (De Pinto et al., 2010; Stadtmuller et al., 1999; Thinnes, 2015) participates in volume regulation, ATP and metabolite transport, and intrinsic mitochondrial apoptosis (Akanda et al., 2008; Okada et al., 2004; Shoshan-Barmatz et al., 2010).”
BackgroundStadtmüller, U., Eben-Brunnen, J., Schmid, A., Hesse, D., Klebert, S., Kratzin, H., Hesse, J., Zimmermann, B. K., Reymann, S., THINNES, F. P., et al. (1999) · Biological Chemistry · doi:10.1515/bc.1999.189 · Cited by 10 · cited 3× · see citing works
“Plasma membrane resident VDAC1 has been documented in various mouse and human tissues with the mitochondrial surface residues facing the extracellular space (Akanda et al., 2008; Buettner et al., 2000; De Pinto et al., 2010; Okada et al., 2004; Stadtmuller et al., 1999; Thinnes, 2015).”
BackgroundMethod
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Sergi, D., Naumovski, N., Heilbronn, L. K., Abeywardena, M., O’Callaghan, N., Lionetti, L., & Luscombe-Marsh, N. (2019) · Frontiers in Physiology · doi:10.3389/fphys.2019.00532 · Cited by 347 · see citing works
“…5 May 2019 | Volume 10 | Article 532 of hyperglycaemic glucotoxicity on mitochondria has also been recently described in pancreatic β cells with glucotoxicity decreasing mitochondrial oxygen consumption rate by inducing the upregulation of voltage-dependent anion channel-1 (Zhang et al., 2019).”
BackgroundInsulin: The Friend and the Foe in the Development of Type 2 Diabetes Mellitus
Rachdaoui, N. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21051770 · Cited by 278 · see citing works
“Mitochondrial coupling of β-cell glucose metabolism to insulin secretion was also shown to be impaired in T2DM and suggested as a contributing factor to β-cell decompensation [17,18].”
BackgroundVDAC1 at the Intersection of Cell Metabolism, Apoptosis, and Diseases
Shoshan‐Barmatz, V., Shteinfer‐Kuzmine, A., & Verma, A. (2020) · Biomolecules · doi:10.3390/biom10111485 · Cited by 232 · see citing works
“Specific anti-VDAC1 antibodies, and our VDAC1 inhibitor, VBIT-4, could restore generation of cellular ATP and normalize glucose-stimulated insulin secretion in T2D islets [84].”
BackgroundInfluentialQuercetin for managing type 2 diabetes and its complications, an insight into multitarget therapy
Dhanya, R. (2021) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2021.112560 · Cited by 180 · see citing works
Lee, H. J., Jung, Y., Choi, G., Kim, J. S., Chang, W.-C., Lim, J. R., Kim, S. Y., Yoon, J., Cho, J. H., Lee, S.-J., et al. (2020) · Cell Death and Differentiation · doi:10.1038/s41418-020-0593-1 · Cited by 1 · see citing works
Metabolic implications of organelle–mitochondria communication
Gordaliza‐Alaguero, I., Cantó, C., & Zorzano, A. (2019) · EMBO Reports · doi:10.15252/embr.201947928 · Cited by 174 · see citing works
“In line with these results, the downregulation of VDAC1 in pancreatic beta-cells has a protective effect against high glucose concentrations and maintains cellular reductive capacity [153].”
InfluentialKoh, A., Mannerås-Holm, L., Yunn, N.-O., Nilsson, P. M., Ryu, S. H., Molinaro, A., Perkins, R., Smith, J. G., & Bäckhed, F. (2020) · Cell Metabolism · doi:10.1016/j.cmet.2020.07.012 · Cited by 160 · see citing works
Nutrient-Induced Metabolic Stress, Adaptation, Detoxification, and Toxicity in the Pancreatic β-Cell
Prentki, M., Peyot, M., Masiello, P., & Madiraju, S. R. M. (2020) · Diabetes · doi:10.2337/dbi19-0014 · Cited by 149 · see citing works
“It was postulated that the overexpression and altered localization of VDAC1 is another mechanism of b-cell glucotoxicity (29), as VDAC1 allows the movement of ATP and causes its cellular loss when present in the cell membrane.”
BackgroundDiabetes Mellitus, Mitochondrial Dysfunction and Ca2+-Dependent Permeability Transition Pore
Belosludtsev, K. N., Belosludtseva, N. V., & Dubinin, M. V. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21186559 · Cited by 122 · see citing works
Verma, A., Pittala, S., Alhozeel, B., Shteinfer‐Kuzmine, A., Ohana, E., Gupta, R., Chung, J. H., & Shoshan‐Barmatz, V. (2021) · Molecular Therapy · doi:10.1016/j.ymthe.2021.06.024 · Cited by 116 · see citing works
Verma, A., Shteinfer‐Kuzmine, A., Kamenetsky, N., Pittala, S., Paul, A., Crystal, E. N., Ouro, A., Caspi, V. C., Pandey, S. K., Monsonego, A., et al. (2022) · Translational Neurodegeneration · doi:10.1186/s40035-022-00329-7 · Cited by 106 · see citing works
“These have been shown for neuro-degenerative diseases [32, 36, 135], type 2 diabetes [42], lupus [26], colitis [43], acute liver injury [136], rheumatoid arthritis [137], and spinal cord injury [138].”
Hu, H., Guo, L., Overholser, J. P., & Wang, X. (2022) · Cells · doi:10.3390/cells11193174 · Cited by 97 · see citing works
“Furthermore, VDAC1 is widely involved in cancer [28,253], neurodegenerative diseases [254,255], diabetes [72,256], kidney disease [257,258], aging [259] and other areas of study.”
BackgroundThioredoxin (Trx): A redox target and modulator of cellular senescence and aging-related diseases
Yang, B., Lin, Y., Huang, Y., Shen, Y.-Q., & Chen, Q. (2024) · Redox Biology · doi:10.1016/j.redox.2024.103032 · Cited by 90 · see citing works
“The expression of TXNIP is induced by glucose and ROS through the activation of carbohydrate response element-binding protein (ChREBP) and mitogen-activated protein kinases (MAPKs), respectively [192 – 194].”
BackgroundMetabolic regulation of calcium signaling in beta cells
Idevall‐Hagren, O., & Tengholm, A. (2020) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2020.01.008 · Cited by 82 · see citing works
Obesity-induced overexpression of miR-802 impairs insulin transcription and secretion
Zhang, F., Ma, D., Zhao, W., Wang, D., Liu, T., Liu, Y., Yang, Y., Liu, Y., Mu, J., Li, B., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-15529-w · Cited by 86 · see citing works
Bcl-2-Protein Family as Modulators of IP 3 Receptors and Other Organellar Ca 2+ ChannelsPreprint
Ivanova, H., Vervliet, T., Monaco, G., Terry, L. E., Rosa, N., Baker, M. R., Parys, J. B., Serysheva, I. I., Yule, D. I., & Bultynck, G. (2019) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a035089 · Cited by 79 · see citing works
Apoptotic proteins with non-apoptotic activity: expression and function in cancer
Shoshan‐Barmatz, V., Arif, T., & Shteinfer‐Kuzmine, A. (2023) · APOPTOSIS · doi:10.1007/s10495-023-01835-3 · Cited by 70 · see citing works
“Although VDAC1 overexpression is associated with apoptosis [17], it is somewhat unexpectedly also overexpressed in cancers [17, 36, 45, 48–50], as well as in other pathologies [36] such as Alzheimer’s disease [51–54], in β-cells in type 2 diabetes [55], and in autoimmune diseases such as lupus [24], inflammatory bowel…”
BackgroundPinto, V. D. (2021) · Biomolecules · doi:10.3390/biom11010107 · Cited by 65 · see citing works
“(V) The involvement of VDAC in many pathologies, from tumors [29] to neurodegenerative diseases like ALS [30], Parkinson’s disease [31], Alzheimer’s disease [32], type 2 diabetes [33], and the identification of it as a potential therapeutic target [34–37].”
BackgroundLi, W., Zeng, H., Xu, M., Huang, C., Tao, L., Li, J., Zhang, T., Chen, H., Xia, J., Li, C., et al. (2021) · Frontiers in Pharmacology · doi:10.3389/fphar.2021.697483 · Cited by 59 · see citing works
“Interestingly, it has been reported that VDAC inhibitors can restore insulin secretion in type 2 diabetes islet donors and prevent hyperglycemia in diabetic mice (Zhang et al., 2019).”
BackgroundTranscriptional mechanisms of pancreatic β-cell maturation and functional adaptation
Wortham, M., & Sander, M. (2021) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2021.04.011 · Cited by 56 · see citing works
“Similarly, the systemic environment of T2D can activate maladaptive transcriptional programs through SDTFs that impair insulin secretion [64,65].”
BackgroundMetabolic roles of G protein‐coupled receptor signaling in obesity and type 2 diabetes
Barella, L. F., Jain, S., Kimura, T., & Pydi, S. P. (2021) · FEBS Journal · doi:10.1111/febs.15800 · Cited by 56 · see citing works
Cysteine Oxidations in Mitochondrial Membrane Proteins: The Case of VDAC Isoforms in Mammals
Reina, S., Pittalà, M. G. G., Guarino, F., Messina, A. A., Pinto, V. D., Foti, S., & Saletti, R. (2020) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.00397 · Cited by 55 · see citing works
Yang, S. S., Zhou, R., Zhang, C., He, S., & Su, Z. (2020) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.571554 · Cited by 55 · see citing works
“In line with these results, silencing VDAC1 in pancreatic islets from diabetic (db/db) mice results in increased ATP production and glucose-stimulated insulin exocytosis in response to high glucose levels (Zhang et al., 2019).”
BackgroundResultHe, X., Gao, F., Hou, J., Li, T., Tan, J., Wang, C., Liu, X., Wang, M., Liu, H., Chen, Y., et al. (2021) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2021.101002 · Cited by 52 · see citing works
“The abbreviations used are: AMPK, AMP-activated protein kinase; AQP7, aquaporin 7; CD36, cluster determinant 36; ERK1/2, extracellular signal-regulated kinases 1/2; FBG, fasting blood glucose; Glu, glucose; GSIS, glucose-stimulated insulin secretion; HE, hematoxylin and eosin; JNK, c-Jun N-terminal kinase; KD, knockdo…”
BackgroundMitochondria and Oxidative Stress as a Link between Alzheimer’s Disease and Diabetes Mellitus
Veselov, I. M., Vinogradova, D. V., Maltsev, A. V., Shevtsov, P. N., Spirkova, E. A., Бачурин, С. О., & Shevtsova, E. F. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms241914450 · Cited by 55 · see citing works
“VDAC dysregulation may be a common mechanism in the development of T2D and NDs [66,67].”
BackgroundMechanisms of gut microbiota-immune-host interaction on glucose regulation in type 2 diabetes
Zhou, Y.-D., Liang, F.-X., Tian, H.-R., Luo, D., Wang, Y., & Yang, S. (2023) · Frontiers in Microbiology · doi:10.3389/fmicb.2023.1121695 · Cited by 45 · see citing works
Zhang, F. F., Liu, Y. H., Wang, D. W., Liu, T. S., Yang, Y., Guo, J., Pan, Y., Zhang, Y. F., Du, H., Li, L., et al. (2020) · Diabetologia · doi:10.1007/s00125-020-05090-y · Cited by 44 · see citing works
“Glucose-stimulated insulin secretion (GSIS) assays of the islets and MIN6 cells were performed as described previously [23].”
Methodβ Cell Dysfunction in Type 2 Diabetes: Drained of Energy?
Knudsen, J. G., & Rorsman, P. (2019) · Cell Metabolism · doi:10.1016/j.cmet.2018.12.015 · Cited by 42 · see citing works
Shoshan‐Barmatz, V., Anand, U., Crystal, E. N., Carlo, M. D., & Shteinfer‐Kuzmine, A. (2021) · Frontiers in Physiology · doi:10.3389/fphys.2021.730048 · Cited by 42 · see citing works
Zhou, X., Tang, X., Li, T., Li, D., Gong, Z., Zhang, X., Li, Y., Zhu, J., Wang, Y., & Zhang, B. (2023) · Mediators of Inflammation · doi:10.1155/2023/6739691 · Cited by 41 · see citing works
Klapper‐Goldstein, H., Verma, A., Elyagon, S., Gillis, R., Murninkas, M., Pittala, S., Paul, A., Shoshan‐Barmatz, V., & Etzion, Y. (2020) · Scientific Reports · doi:10.1038/s41598-020-79056-w · Cited by 43 · see citing works
Yang, J., Xiao, L., Hao, J., Li, L., Ruan, Y.-T., An, X.-N., Huang, Q., Dong, X., & Gao, P. H. (2025) · Nature Communications · doi:10.1038/s41467-025-56494-6 · Cited by 46 · see citing works
“To explore whether VSTM2L suppression contributed to the fer-roptosis of PCa cells through regulating oligomerization of VDAC1, we employed a VDAC1 oligomerization inhibitor, VBIT4 55,56 , in our subsequent studies.”
The role of mitochondrial-related nuclear genes in age-related common disease
Li, H., Slone, J. D., & Huang, T. (2020) · Mitochondrion · doi:10.1016/j.mito.2020.04.012 · Cited by 41 · see citing works
Chareyron, I., Christen, S., Moco, S., Valsesia, A., Lassueur, S., Dayon, L., Wollheim, C. B., Domingo, J. S., & Wiederkehr, A. (2020) · Diabetologia · doi:10.1007/s00125-020-05275-5 · Cited by 38 · see citing works
“The observed reduction in insulin content and diminished glucose-induced insulin secretion are consistent with findings from earlier studies [27, 29, 35, 36, 49].”
BackgroundResultPalanisamy, S., Yien, E. L. H., Shi, L., Yi, L., Qi, S. H., Soon, L., Lun, T. W., & Chen, Y. N. (2018) · Pharmacy · doi:10.3390/pharmacy6030057 · Cited by 37 · see citing works
Xie, J., Cui, Y., Chen, X., Yu, H., Chen, J., Huang, T., He, M., Zhang, L., & Meng, Q. (2021) · Experimental Eye Research · doi:10.1016/j.exer.2021.108640 · Cited by 36 · see citing works
The functional impact of G protein-coupled receptor 142 (Gpr142) on pancreatic β-cell in rodent
Al-Amily, I. M., Dunér, P., Groop, L., & Salehi, A. A. (2019) · Pflügers Archiv - European Journal of Physiology · doi:10.1007/s00424-019-02262-7 · Cited by 35 · see citing works
GNAS gene is an important regulator of insulin secretory capacity in pancreatic β-cells
Taneera, J., Dhaiban, S., Mohammed, A. K., Mukhopadhyay, D., Aljaibeji, H., Sulaiman, N. D., Fadista, J., & Salehi, A. A. (2019) · Gene · doi:10.1016/j.gene.2019.144028 · Cited by 35 · see citing works
Nguyen, H. T., Polo, C. N., Wiederkehr, A., Wollheim, C. B., & Park, K. (2023) · British Journal of Pharmacology · doi:10.1111/bph.16160 · Cited by 35 · see citing works
“Moreover, in such diabetic β -cells, VDAC1 is mistargeted to the plasma membrane, causing ATP depletion and impaired insulin secretion (E. Zhang et al., 2019).”
BackgroundTubular Mas receptor mediates lipid-induced kidney injury
Kong, Y., Zhao, X., Qiu, M., Lin, Y., Feng, P., Li, S., Liang, B., Zhu, Q., Huang, H., Li, C., et al. (2021) · Cell Death and Disease · doi:10.1038/s41419-020-03375-z · Cited by 33 · see citing works
Targeting the Mitochondrial Protein VDAC1 as a Potential Therapeutic Strategy in ALS
Shteinfer‐Kuzmine, A., Argueti-Ostrovsky, S., Leyton-Jaimes, M. F., Anand, U., Abu‐Hamad, S., Zalk, R., Shoshan‐Barmatz, V., & Israelson, A. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23179946 · Cited by 33 · see citing works
“We previously demonstrated that VBIT-4 treatment via drinking water is well tolerated in mice [43,55,56].”
BackgroundMethodInfluentialNandwani, A., Rathore, S., & Datta, M. (2023) · Redox Biology · doi:10.1016/j.redox.2023.102989 · Cited by 33 · see citing works
“These were additionally validated using metformin, a commonly used antidiabetic medication that acts by inhibiting VDAC1 levels [41].”
BackgroundMethodVDAC1: A Key Player in the Mitochondrial Landscape of Neurodegeneration
Argueti-Ostrovsky, S., Barel, S., Kahn, J., & Israelson, A. (2024) · Biomolecules · doi:10.3390/biom15010033 · Cited by 31 · see citing works
“These compounds have been shown to prevent mitochondrial dysfunction and apoptosis in various mouse models with VDAC1 overexpressed, including type 2 diabetes [52], lupus [53], and colitis (Table 1) [54].”
Tau suppresses microtubule-regulated pancreatic insulin secretion
Mangiafico, S. P., Tuo, Q., Li, X.-L., Liu, Y., Haralambous, C., Ding, X., Ayton, S., Wang, Q., Laybutt, D. R., Chan, J. Y., et al. (2023) · Molecular Psychiatry · doi:10.1038/s41380-023-02267-w · Cited by 32 · see citing works
“GSIS in INS-1 cells was determined as described previously [26].”
Yin, L., Qi, S., & Zhu, Z. (2023) · Frontiers in Endocrinology · doi:10.3389/fendo.2023.1267170 · Cited by 32 · see citing works
Pharmacological inhibitors of β-cell dysfunction and death as therapeutics for diabetes
Dalle, S., Abderrahmani, A., & Renard, É. (2023) · Frontiers in Endocrinology · doi:10.3389/fendo.2023.1076343 · Cited by 29 · see citing works
“Treatment of db/db mice with VDAC1 inhibitor VBIT-4 prevented hyperglycemia, and maintained b-cell function and glucose tolerance (96).”
BackgroundInfluentialDYRK1A Kinase Inhibitors Promote β-Cell Survival and Insulin Homeostasis
Barzowska, A., Pucelik, B., Pustelny, K., Matsuda, A., Martyniak, A., Stępniewski, J., Maksymiuk, A., Dawidowski, M., Rothweiler, U., Dulak, J., et al. (2021) · Cells · doi:10.3390/cells10092263 · Cited by 27 · see citing works
“IT) [14], INDY [15] and benzothiazoles derivatives [16], azaindoles and aminopyrazines such as GNF-4877 [17–19], VBIT-4, G-1 [3,4] (Figure S1).”
BackgroundXian, T., Liu, Y., Ye, Y., Peng, B., Huang, J., Liang, L., Zhang, J., Wu, H. B., & Lin, Z. (2024) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2024.09.046 · Cited by 25 · see citing works
Taneera, J., Mohammed, I., Mohammed, A. K., Hachim, M. Y., Dhaiban, S., Malek, A. I., Dunér, P., Elemam, N. M., Sulaiman, N. D., Hamad, M. A., et al. (2019) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2019.110592 · Cited by 24 · see citing works
Regulation of autophagy by perilysosomal calcium: a new player in β-cell lipotoxicity
Nguyen, H. T., Wiederkehr, A., Wollheim, C. B., & Park, K. (2024) · Experimental & Molecular Medicine · doi:10.1038/s12276-024-01161-x · Cited by 24 · see citing works
“The acute restoration of insulin secretion by metformin is caused by inhibition of voltage-dependent anion channel-1 (VDAC1), which is mistargeted to the β -cell plasma membrane in diabetes 60 .”
BackgroundLi, J., Yan, H., Xiang, R., Yang, W., Ye, J., Yin, R., Yang, J., & Chi, Y. (2022) · Frontiers in Physiology · doi:10.3389/fphys.2022.918042 · Cited by 24 · see citing works
“So far, it had been widely acknowledged that islet β cell dysfunctions and insulin resistance are the two key factors causing T2DM (Bensellam et al., 2018; Holst et al., 2018; Zhang et al., 2019).”
BackgroundThe VDAC1-based R-Tf-D-LP4 Peptide as a Potential Treatment for Diabetes Mellitus
Pittala, S., Levy, I., De, S., Pandey, S. K., Melnikov, N., Hyman, T., & Shoshan‐Barmatz, V. (2020) · Cells · doi:10.3390/cells9020481 · Cited by 23 · see citing works
Is Type 2 Diabetes a Primary Mitochondrial Disorder?
Weksler‐Zangen, S. (2022) · Cells · doi:10.3390/cells11101617 · Cited by 22 · see citing works
Zhang, W., Sakoda, H., & Nakazato, M. (2019) · The FASEB Journal · doi:10.1096/fj.201901743r · Cited by 21 · see citing works
“Aberrant insertion of a mitochondrial voltage-dependent anion channel in the plasma membrane of β-cells is an important event in type 2 diabetes (18).”
BackgroundRetnakaran, R. R., Choi, H., Ye, C., Kramer, C. K., & Zinman, B. (2018) · Diabetes Obesity and Metabolism · doi:10.1111/dom.13236 · Cited by 21 · see citing works
D’Amico, A. G., Maugeri, G., Magrì, B., Bucolo, C., & D’Agata, V. (2024) · Experimental Eye Research · doi:10.1016/j.exer.2024.110024 · Cited by 20 · see citing works
Role of ferroptosis inhibitors in the management of diabetes
Krishna Prasad, M., Mohandas, S., & Ramkumar, K. M. (2022) · BioFactors · doi:10.1002/biof.1920 · Cited by 22 · see citing works
“In addition, it was reported that VDAC1 inhibitors improved the insulin secretion levels, and also attenuated hyperglycemic effects in diabetic mice models.(62) Another study revealed that VDAC1 expression was elevated, while VDAC2 expression was reduced in rat pancreatic beta cells cultured in hyperglycemic condition…”
BackgroundBelosludtsev, K. N., Serov, D. A., Ilzorkina, A. I., Starinets, V. S., Dubinin, M. V., Talanov, E. Y., Karagyaur, M. N., Primak, A. L., & Belosludtseva, N. V. (2023) · Antioxidants · doi:10.3390/antiox12071459 · Cited by 20 · see citing works
“A number of studies have shown that the development of diabetes mellitus is accompanied by an increase in VDAC1 expression, which may be one of the factors in the development of this pathology [23,24].”
BackgroundInfluentialBelosludtseva, N. V., Dubinin, M. V., & Belosludtsev, K. N. (2024) · Biochemistry (Moscow) · doi:10.1134/s0006297924060075 · Cited by 20 · see citing works
“The development of diabetes mellitus is accompanied by changes in the content of VDAC1 in the mitochondria, which may be one of the pathogenetic factors in this pathology [4, 12, 28, 144].”
InfluentialMarchi, U. D., Fernandez‐Martinez, S., de la Fuente, S., Wiederkehr, A., & Domingo, J. S. (2020) · British Journal of Pharmacology · doi:10.1111/bph.15018 · Cited by 20 · see citing works
The glucose-lowering effects of α-glucosidase inhibitor require a bile acid signal in mice
Qiu, Y., Shen, L., Fu, L., Yang, J., Cui, C., Li, T., Li, X., Fu, C., Gao, X., Wang, W., et al. (2020) · Diabetologia · doi:10.1007/s00125-020-05095-7 · Cited by 18 · see citing works
Decoding Cancer through Silencing the Mitochondrial Gatekeeper VDAC1
Arif, T., Shteinfer‐Kuzmine, A., & Shoshan‐Barmatz, V. (2024) · Biomolecules · doi:10.3390/biom14101304 · Cited by 21 · see citing works
“This overexpression is observed in cancer [1,19,54,75,121,154], Alzheimer’s disease (AD) [65,155–157], type 2 diabetes (T2DM) [64,158,159], autoimmune diseases such as lupus [62], cardiovascular diseases [160–168], inflammatory bowel diseases (IBDs) [61], non-alcoholic fatty liver disease (NAFLD)…”
BackgroundSignaling architecture of the glucagon-like peptide-1 receptor
Austin, G. O., & Tomás, A. (2026) · Journal of Clinical Investigation · doi:10.1172/jci194752 · Cited by 20 · see citing works
“VDAC is known to play important roles in the control of ER-to-mitochondria Ca 2+ transfer (73) and ATP flux (74) both in β cells and in neurons, with T2D defects associated with VDAC1 mistargeting, which causes loss of ATP flux, mitochondrial Ca 2+ dysregulation, and impaired insulin secretion (75).”
Jeyarajan, S., Zhang, I. X., Arvan, P. R., Lentz, S. I., & Satin, L. S. (2023) · Biosensors · doi:10.3390/bios13030382 · Cited by 17 · see citing works
“To determine whether raising the cytosolic Ca2+ in turn affected the ER and mitochondrial Ca2+, we added 30 mM KCl to the INS1-832/13 cells to depolarize them to open the voltage-gated Ca2+ channels (VDAC) [51].”
BackgroundZhang, T., Cao, R.-J., Niu, J.-L., Chen, Z., Mu, S.-Q., Cao, T., Pang, J.-X., & Dong, L. (2024) · Cellular & Molecular Biology Letters · doi:10.1186/s11658-024-00566-w · Cited by 17 · see citing works
“On the other hand, a decrease in apoptosis is typically associated with a reduction in VDAC1 oligomerization [49, 50].”
BackgroundHong, Y., Chen, Y.-X., Linghu, K., Ren, P.-Y., Yao, Y.-T., Jiang, F., Wu, G., Chen, T., Ji, Y., Tao, L., et al. (2024) · Phytomedicine · doi:10.1016/j.phymed.2024.156099 · Cited by 17 · see citing works
Yang, H., Wang, Z., Hu, S., Chen, L., Li, W., & Yang, Z. (2023) · Aging · doi:10.18632/aging.204474 · Cited by 16 · see citing works
“mitochondria, and VDAC1 regulates energy and metabolism [30].”
BackgroundEffect of VBIT-4 on the functional activity of isolated mitochondria and cell viability
Belosludtsev, K. N., Ilzorkina, A. I., Matveeva, L. A., Chulkov, A. V., Semenova, A. A., Dubinin, M. V., & Belosludtseva, N. V. (2024) · Biochimica et Biophysica Acta (BBA) - Biomembranes · doi:10.1016/j.bbamem.2024.184329 · Cited by 19 · see citing works
Ma, Y., Yang, W., Liang, P., Feng, R., Qiu, T., Zhang, J., Sun, X., Li, Q., Yang, G., & Yao, X. (2024) · Ecotoxicology and Environmental Safety · doi:10.1016/j.ecoenv.2024.116647 · Cited by 17 · see citing works
Han, A., Peng, T., Xie, Y., Zhang, W., Sun, W., Xie, Y., Ma, Y., Wang, C., & Xie, N. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1301074 · Cited by 15 · see citing works
“This VDAC1-based treatment strategy has been effective in some animal models of autoimmune diseases, such as in fl ammatory bowel disease, systemic lupus erythematosus, and type 2 diabetes (97, 98, 105).”
MethodXu, R., Li, S., Shi, M., Li, Z., Wang, Y., Li, J., Li, Q., Klausen, L. H., Li, A., Zhao, H., et al. (2020) · Nano Today · doi:10.1016/j.nantod.2020.101054 · Cited by 15 · see citing works
Wei, S., Zhang, H., Lü, Y., Yu, H., Ma, T., Wang, S., Yang, K., Tian, M., Huang, A., Wang, W., et al. (2023) · SLEEP · doi:10.1093/sleep/zsad039 · Cited by 17 · see citing works
Zhang, S., Xie, W., Zhai, Z.-Q., Chen, C., Zhao, F. J., & Wang, P. (2023) · Environmental Pollution · doi:10.1016/j.envpol.2023.121553 · Cited by 14 · see citing works
Dalle, S., & Abderrahmani, A. (2024) · Cells · doi:10.3390/cells13151244 · Cited by 14 · see citing works
“The treatment of db/db mice VBIT-4 reduced the emergence of hyperglycemia and maintained their beta-cell function and glucose tolerance [216].”
BackgroundMetformin Perturbs Pancreatic Differentiation From Human Embryonic Stem Cells
Nguyen, L. T. V., Lim, L. Y., Ding, S. S. L., Amirruddin, N. S., Hoon, S. S., Chan, S., & Teo, A. K. K. (2021) · Diabetes · doi:10.2337/db20-0722 · Cited by 16 · see citing works
Karunakaran, U., Elumalai, S., Moon, J. S., & Won, K. C. (2022) · Translational research · doi:10.1016/j.trsl.2022.06.007 · Cited by 14 · see citing works
Gorny, H., Mularoni, A., Delcros, J., Freton, C., Preto, J., & Krimm, I. (2023) · Journal of Enzyme Inhibition and Medicinal Chemistry · doi:10.1080/14756366.2022.2121821 · Cited by 14 · see citing works
Al-Amily, I. M., Sjögren, M., Dunér, P., Mohammad, T., Wollheim, C. B., & Salehi, A. A. (2023) · Biomolecules · doi:10.3390/biom13030557 · Cited by 13 · see citing works
“Vdac1 is an ATP-conducting anion channel normally allowing the transport of ATP from mitochondria to the cytoplasm in cells [11,14].”
BackgroundResultInfluentialSuleiman, M., Sawatani, T., Tesi, M., Yi, X., Papadopoulou, T. A., Rufer, C., Lytrivi, M., Bosi, E., Burdet, F., Fantuzzi, F., et al. (2025) · Science Advances · doi:10.1126/sciadv.ads2905 · Cited by 12 · see citing works
“…responsiveness, accompanied by better ultrastructural features, changes in expression of genes associated with cellular redox balance, and reduced induction of the adenosine 5 ′ - triphosphate (ATP)–conducting mitochondrial outer membrane voltage-dependent anion channel-1 (VDAC1) ( 16 , 17 ).”
Shteinfer‐Kuzmine, A., Verma, A., Bornshten, R., Chetrit, E. B., Yaʼacov, A. B., Pahima, H. T., Rubin, E., Mograbi, Y., Shteyer, E., & Shoshan‐Barmatz, V. (2024) · APOPTOSIS · doi:10.1007/s10495-024-02025-5 · Cited by 13 · see citing works
“…and apoptosis were triggered by various apoptosis-inducing conditions including chemotherapy drugs and UV irradiation [16–18, 20, 94] in several disorders such as Alzheimer’s disease [95], type 2 diabetes [96], and autoimmune diseases such as lupus [23] and inflammatory bowel diseases [97].”
Cytochrome c Oxidase Activity as a Metabolic Regulator in Pancreatic Beta-Cells
Aharon‐Hananel, G., Romero, L., Saada, A., Mantzur, C., Raz, I., & Weksler‐Zangen, S. (2022) · Cells · doi:10.3390/cells11060929 · Cited by 12 · see citing works
Functional Relationship of Arabidopsis AOXs and PTOX Revealed via Transgenic Analysis
Wang, D., Wang, C., Li, C., Song, H., Qin, J., Chang, H., Fu, W., Wang, Y., Wang, F., Li, B., et al. (2021) · Frontiers in Plant Science · doi:10.3389/fpls.2021.692847 · Cited by 12 · see citing works
“It has been reported that some of the overexpressed proteins could be mis-targeted to wrong organelles (Lisenbee et al., 2003; Vitali et al., 2018; Zhang et al., 2019).”
BackgroundRaviv, T., Shteinfer‐Kuzmine, A., Moyal, M. M., & Shoshan‐Barmatz, V. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26093963 · Cited by 11 · see citing works
“…(Figure In this content, VDAC1 overexpression has been implicated in many diseases including cancer, Alzheimer’s disease (AD) [69–72], Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS) [73,74], type 2 diabetes (T2D) [75–77], cardiovascular diseases [78,79], and autoimmune diseases [80].”
Chebulic Acid Prevents Methylglyoxal-Induced Mitochondrial Dysfunction in INS-1 Pancreatic β-Cells
Yoo, H.-J., Hong, C., Ha, S. K., & Lee, K. (2020) · Antioxidants · doi:10.3390/antiox9090771 · Cited by 11 · see citing works
Inhibitory effect of UDP-glucose on cAMP generation and insulin secretion
Parandeh, F., Amisten, S., Verma, G., Al-Amily, I. M., Dunér, P., & Salehi, A. A. (2020) · Journal of Biological Chemistry · doi:10.1074/jbc.ra120.012929 · Cited by 11 · see citing works
“Colocalization analysis of islet P2Y14 with insulin (indicator of β-cells) in islets was performed using the ZEN2009 software based on Pearson’s coefficient analysis, which recognizes the co-localized pair by comparison pixel by pixel intensity (19,27,30).”
MethodResultInfluentialFourny, N., Lan, C., Bernard, M., & Desrois, M. (2021) · Nutrients · doi:10.3390/nu13092914 · Cited by 11 · see citing works
“This is a reversible condition preceding well-established type 2 diabetes [3], highly related to sedentary lifestyle and consumption of high fat and/or high sucrose diet.”
BackgroundShen, Y., Si, Y., Lu, J., Ma, X., Zhang, L., Mo, Y., Lu, W., Zhu, W., Bao, Y., Hu, G., et al. (2020) · Journal of Diabetes Research · doi:10.1155/2020/4243053 · Cited by 10 · see citing works
“A recently reported study demonstrated that β-cell metabolism-secretion coupling could be decreased by glucotoxicity via a novel mechanism [5].”
BackgroundRab26 restricts insulin secretion via sequestering Synaptotagmin-1
Zhuang, R., Zhou, Y., Wang, Z., Cao, Y., Chen, J., Xu, L., Ren, Y., Zheng, Y., Wei, Z., Qiu, H., et al. (2023) · PLoS Biology · doi:10.1371/journal.pbio.3002142 · Cited by 10 · see citing works
“Dysfunction in mitochondria with loss of ATP also results in the impaired glucose-stimulated insulin secretion [6].”
BackgroundStructural insights into human EMC and its interaction with VDAC
Li, M., Zhang, C., Xu, Y., Li, S., Huang, C., Wu, J., & Lei, M. (2024) · Aging · doi:10.18632/aging.205660 · Cited by 7 · see citing works
“Intriguingly, there is an increase in the translocation of VDAC1 under certain pathological conditions [46, 52].”
Pan, X., Olatunji, O. J., Basit, A., Sripetthong, S., Nalinbenjapun, S., & Ovatlarnporn, C. (2024) · Frontiers in Pharmacology · doi:10.3389/fphar.2024.1424346 · Cited by 9 · see citing works
Belosludtseva, N. V., Ilzorkina, A. I., Serov, D. A., Dubinin, M. V., Talanov, E. Y., Karagyaur, M. N., Primak, A. L., Liu, J., & Belosludtsev, K. N. (2024) · Biomolecules · doi:10.3390/biom14091159 · Cited by 9 · see citing works
Zhang, J., Li, D., Zhou, L., Li, Y., Xi, Q., Zhang, L.-Y., & Zhang, J. (2025) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2025.1629568 · Cited by 9 · see citing works
Gautier, B., Jacquard, M. F., Guelfi, S., Abbou, S., Gonzalez, E., Berthelot, J., Boukhaddaoui, H., Lebrun, A., Legrand, B., Tricaud, N., et al. (2022) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.2c00411 · Cited by 9 · see citing works
Metabolomics of Mice with Type 2 Diabetes and Nonalcoholic Fatty Liver Treated by Acupuncture
Guo, Y., Zhang, L., Li, M., Lin, L., Xue, F., Gao, W., Xu, X., & Huang, H. (2024) · International Journal of Endocrinology · doi:10.1155/2024/5568337 · Cited by 8 · see citing works
VDAC1 is a target for pharmacologically induced insulin hypersecretion in β cells
Roy, G., Ordonez, A. D., Binns, D. D., Rodrigues-dos-Santos, K., Kwakye, M. B., King, G. C., Kuntz, R., Mukherjee, N., Templin, A. T., Tan, Z., et al. (2025) · Cell Reports · doi:10.1016/j.celrep.2025.115834 · Cited by 7 · see citing works
Preservation of β-Cells as a Therapeutic Strategy for Diabetes
Taneera, J., & Saber-Ayad, M. M. (2024) · Hormone and Metabolic Research · doi:10.1055/a-2239-2668 · Cited by 10 · see citing works
“Inhibition of VDAC1 conductance using metformin and specific VDAC1 inhibitors has been shown to restore ATP generation and glucose-stimulated insulin secretion in T2D pancreatic islets, protecting β-cells from glucotoxicity [71].”
Carrasco, M., Wang, C., Søviknes, A. M., Bjørlykke, Y., Abadpour, S., Paulo, J. A., Tjora, E., Njølstad, P. R., Ghabayen, J., Nermoen, I., et al. (2022) · Diabetes · doi:10.2337/db20-1279 · Cited by 8 · see citing works
“The OCR values were normalized to the average baseline values measured in assay media containing 1.67 mmol/L glucose.”
MethodInfluentialCo-exposure to multiple vitamins and the risk of all-cause mortality in patients with diabetes
Zhou, L., Zhang, J., Zhang, D., Ye, Y., Jiang, M., Liu, H., Li, J., Li, M., Zhang, Z., & Guo, L. (2023) · Frontiers in Endocrinology · doi:10.3389/fendo.2023.1254133 · Cited by 7 · see citing works
“Vitamin D can act directly on pancreatic b-cells, affecting insulin secretion (32, 33), improve insulin sensitivity through vitamin D receptors in insulin-sensitive organs (34), and reduce oxidative stress in patients with diabetes (22).”
BackgroundNoncanonical Regulation of cAMP-dependent Insulin Secretion and Its Implications in Type 2 Diabetes
Ramanadham, S., Turk, J., & Bhatnagar, S. (2023) · Comprehensive Physiology · doi:10.1002/j.2040-4603.2023.tb00278.x · Cited by 10 · see citing works
“This triggering of the exocytotic process releases a short but robust burst of insulin for the first 10 min of glucose stimulation (16, 158, 395).”
VDAC1 Inhibition Protects Against Noise‐Induced Hearing Loss via the PINK1 /Parkin Pathway
Jin, Y., Dong, W., Jiang, Y., Dong, L., Li, Z., & Yu, D. (2025) · CNS Neuroscience & Therapeutics · doi:10.1111/cns.70410 · Cited by 6 · see citing works
“In type 2 diabetes, VDAC1 is overexpressed in pancreatic β-cells and is linked to impaired cellular ATP generation, both of which may contribute to β-cell dysfunction and insulin resistance [42].”
- Authors
- Zhang, E., Mohammed Al-Amily, I., Mohammed, S., Luan, C., Asplund, O., Ahmed, M., Ye, Y., Ben-Hail, D., Soni, A., Vishnu, N., Bompada, P., De Marinis, Y., Groop, L., Shoshan-Barmatz, V., Renström, E., Wollheim, C. B., & Salehi, A.
- Affiliations
- Lund University (SE)
- Uppsala University (SE)
- Ben-Gurion University of the Negev (IL)
- University of Helsinki (FI)
- University of Geneva (CH)
- Corresponding author
- Wollheim, Claes B.
- Salehi, Albert
- ORCID
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2019-01
- Volume
- 29
- Issue
- 1
- Pages
- 64-77.e6
- ISSN
- 1550-4131 (ISSN-L)
- PMC
- PMC6331340
- OpenAlex
- W2894698210
- Cited by
- 171
- References
- 55
- Citations by year
- 2026: 18 · 2025: 21 · 2024: 30 · 2023: 28 · 2022: 17 · 2021: 18 · 2020: 27 · 2019: 10 · 2018: 2
- FWCI
- 14.81
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Cell Metabolism (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Archive ouverte UNIGE (University of Geneva) (publishedVersion, other-oa)
- Työväentutkimus Vuosikirja (submittedVersion)
- Lund University Publications (Lund University) (submittedVersion)
- Archive ouverte UNIGE (University of Geneva) (submittedVersion, cc-by)
- Funders
- Sweden, Öresund Diabetes Academy
- Mats Paulsson Foundation
- Forget foundation
- Bo and Kerstin Hjelt foundation
- Lund University
- Crafoord Foundation
- Israel Science Foundation
- Sima and Philip Needleman research
- ERC Advanced Researcher (GA269045)
- Knut and Alice Wallenberg Foundation
- Swedish Research Council (Dnr 349-2006-237)
- Swedish Diabetes Association
- Diabetes Wellness Sweden Foundation
- ALF
- Strategic Research Area Exodiab (Dnr 2009-1039)
- Strategic Research LUDC-IRC (Dnr IRC15-0067)
- Topics
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Keywords
- VDAC1, type 2 diabetes, insulin secretion, pancreatic beta cells, glucotoxicity, prediabetes, metformin, mitochondrial ATP, mitochondrial outer membrane, glucose-stimulated insulin secretion, islets, db/db mice, glucose tolerance
- MeSH terms
- Insulin Secretion, Animals, Diabetes Mellitus, Type 2, Glucose, Humans, Hyperglycemia, Insulin, Metformin, Cell Line, Tumor, Insulin-Secreting Cells, Voltage-Dependent Anion Channel 1, Mice
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