Caloric restriction recovers impaired β-cell-β-cell gap junction coupling, calcium oscillation coordination, and insulin secretion in prediabetic mice

Corezola do Amaral, Maria Esméria; Kravets, Vira; Dwulet, JaeAnn M.; Farnsworth, Nikki L.; Piscopio, Robert; Schleicher, Wolfgang E.; Miranda, Jose Guadalupe; Benninger, Richard K. P.

doi:10.1152/ajpendo.00132.2020

Cited by 41Pancreatic function and diabetesConnexins and lens biologyDiabetes Treatment and Management

Caloric restriction recovers impaired β-cell-β-cell gap junction coupling, calcium oscillation coordination, and insulin secretion in prediabetic mice

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Corezola do Amaral, Maria Esméria, Kravets, Vira, Dwulet, JaeAnn M., Farnsworth, Nikki L., Piscopio, Robert, Schleicher, Wolfgang E., Miranda, Jose Guadalupe, Benninger, Richard K. P.·2020·American Journal of Physiology-Endocrinology and Metabolism

DOI 10.1152/ajpendo.00132.2020PMC PMC7750515

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Abstract

Abstract Caloric restriction has been shown to decrease the incidence of metabolic diseases such as obesity and type 2 diabetes mellitus (T2DM). The mechanisms underlying the benefits of caloric restriction involved in insulin secretion and glucose homeostasis and are not fully understood. Intercellular communication within the islets of Langerhans, mediated by Connexin36 (Cx36) gap junctions, regulates insulin secretion dynamics and glucose homeostasis. The goal of this study was to determine if caloric restriction can protect against decreases in Cx36 gap junction coupling and altered islet function induced in models of obesity and prediabetes. C57BL6 mice were fed with a high fat diet (HFD), showing indications of prediabetes after 2 months, including weight gain, insulin resistance, and elevated fasting glucose and insulin levels. Subsequently, mice were submitted to one month of 40% caloric restriction (2g/day of HFD). Mice under 40% caloric restriction showed reversal in weight gain and recovered insulin sensitivity, fasting glucose and insulin levels. In islets of mice fed the HFD, caloric restriction protected against obesity-induced decreases in gap junction coupling and preserved glucose-stimulated calcium signaling, including Ca 2+ oscillation coordination and oscillation amplitude. Caloric restriction also promoted a slight increase in glucose metabolism, as measured by increased NAD(P)H autofluorescence, as well as recovering glucose-stimulated insulin secretion. We conclude that declines in Cx36 gap junction coupling that occur in obesity can be completely recovered by caloric restriction and obesity reversal, improving Ca 2+ dynamics and insulin secretion regulation. This suggests a critical role for caloric restriction in the context of obesity to prevent islet dysfunction.

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Long term >40% caloric restriction recovered insulin sensitivity, fasting glucose, and insulin levels.
“long term >40% caloric restriction recovered insulin sensitivity, fasting glucose, and insulin levels”
From The cardioprotective effects of semaglutide exceed those of dietary weight loss in mice with HFpEF (2023) · cites this paper as [61]

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Global aetiology and epidemiology of type 2 diabetes mellitus and its complications
Zheng, Y., Ley, S. H., & Hu, F. B. (2018) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2017.151 · Cited by 5,697 · see citing works
Use and Abuse of HOMA Modeling
Wallace, T. M., Levy, J. C., & Matthews, D. R. (2004) · Diabetes Care · doi:10.2337/diacare.27.6.1487 · Cited by 5,114 · see citing works
Men and mice: Relating their ages
Dutta, S., & Sengupta, P. (2016) · Life Sciences · doi:10.1016/j.lfs.2015.10.025 · Cited by 1,710 · see citing works
Reversal of type 2 diabetes: normalisation of beta cell function in association with decreased pancreas and liver triacylglycerol
Lim, E. L., Hollingsworth, K. G., Aribisala, B. S., Chen, M. J., Mathers, J. C., & Taylor, R. (2011) · Diabetologia · doi:10.1007/s00125-011-2204-7 · Cited by 1,164 · see citing works
Durability of a primary care-led weight-management intervention for remission of type 2 diabetes: 2-year results of the DiRECT open-label, cluster-randomised trial
Lean, M. E. J., Leslie, W. S., Barnes, A. C., Brosnahan, N., Thom, G., McCombie, L., Peters, C., Zhyzhneuskaya, S., Al-Mrabeh, A., Hollingsworth, K. G., et al. (2019) · The Lancet Diabetes & Endocrinology · doi:10.1016/s2213-8587(19)30068-3 · Cited by 981 · see citing works
Standard operating procedures for describing and performing metabolic tests of glucose homeostasis in mice
Ayala, J. E., Samuel, V. T., Morton, G. J., Obici, S., Croniger, C. M., Shulman, G. I., Wasserman, D. H., & McGuinness, O. P. (2010) · Disease Models & Mechanisms · doi:10.1242/dmm.006239 · Cited by 722 · see citing works
The Importance of -Cell Failure in the Development and Progression of Type 2 Diabetes
Kahn, S. E. (2001) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.86.9.7713 · Cited by 694 · see citing works
Caloric Restriction Mimetics against Age-Associated Disease: Targets, Mechanisms, and Therapeutic Potential
Madeo, F., Carmona-Gutierrez, D., Hofer, S. J., & Kroemer, G. (2019) · Cell Metabolism · doi:10.1016/j.cmet.2019.01.018 · Cited by 630 · see citing works
Estimates ofIn VivoInsulin Action in Man: Comparison of Insulin Tolerance Tests with Euglycemic and Hyperglycemic Glucose Clamp Studies*
Bonora, E., Moghetti, P., Zancanaro, C., CIGOLINI, M., Querena, M., Cacciatori, V., Corgnati, A., & Muggeo, M. (1989) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem-68-2-374 · Cited by 525 · see citing works
Loss of Connexin36 Channels Alters β-Cell Coupling, Islet Synchronization of Glucose-Induced Ca2+ and Insulin Oscillations, and Basal Insulin Release
Ravier, M. A., Güldenagel, M., Charollais, A., Gjinovci, A., Caille, D., Söhl, G., Wollheim, C. B., Willecke, K., Henquin, J.-C., & Meda, P. (2005) · Diabetes · doi:10.2337/diabetes.54.6.1798 · Cited by 360 · see citing works
β Cell dysfunction during progression of metabolic syndrome to type 2 diabetes
Hudish, L. I., Reusch, J. E. B., & Sussel, L. (2019) · Journal of Clinical Investigation · doi:10.1172/jci129188 · Cited by 343 · see citing works
Oscillations of secretion driven by oscillations of cytoplasmic Ca2+ as evidences in single pancreatic islets.
Gilon, P., Shepherd, R. M., & Henquin, J. C. (1993) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)41522-0 · Cited by 329 · see citing works
Selective Inhibition of Eukaryotic Translation Initiation Factor 2α Dephosphorylation Potentiates Fatty Acid-induced Endoplasmic Reticulum Stress and Causes Pancreatic β-Cell Dysfunction and Apoptosis
Cnop, M., Ladrière, L., Hekerman, P., Ortis, F., Cardozo, A. K., Doğusan, Z., Flamez, D., Boyce, M., Yuan, J., & Eizirik, D. L. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m607627200 · Cited by 287 · see citing works
Exposing the exposures responsible for type 2 diabetes and obesity
Franks, P. W., & McCarthy, M. I. (2016) · Science · doi:10.1126/science.aaf5094 · Cited by 265 · see citing works
Synchronous oscillations of cytoplasmic Ca2+ and insulin release in glucose-stimulated pancreatic islets.
Bergsten, P., Grapengiesser, E., Gylfe, E., Tengholm, A., & Hellman, B. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)37032-1 · Cited by 260 · see citing works
Influence of membrane potential changes on cytoplasmic Ca2+ concentration in an electrically excitable cell, the insulin-secreting pancreatic B-cell.
Gilon, P., & Henquin, J. C. (1992) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)36744-4 · Cited by 251 · see citing works
Gap Junction Coupling and Calcium Waves in the Pancreatic Islet
Benninger, R. K. P., Zhang, M., Head, W. S., Satin, L. S., & Piston, D. W. (2008) · Biophysical Journal · doi:10.1529/biophysj.108.140863 · Cited by 240 · see citing works
Natural history of β-cell adaptation and failure in type 2 diabetes
Alejandro, E. U., Gregg, B. E., Blandino-Rosano, M., CRAS-MÉNEUR, C. M. H., & Bernal‐Mizrachi, E. (2014) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2014.12.002 · Cited by 235 · see citing works
Health Benefits of Fasting and Caloric Restriction
Golbidi, S., Daiber, A., Korać, B., Li, H., Essop, M. F., & Laher, I. (2017) · Current Diabetes Reports · doi:10.1007/s11892-017-0951-7 · Cited by 218 · see citing works
Calcium signaling in pancreatic β-cells in health and in Type 2 diabetes.
Gilon, P., Chae, H., Rutter, G., & Ravier, M. (2014) · Cell Calcium · doi:10.1016/j.ceca.2014.09.001 · Cited by 212 · see citing works
Lipotoxicity disrupts incretin-regulated human β cell connectivity
Hodson, D. J., Mitchell, R. K., Bellomo, E. A., Sun, G., Vinet, L., Meda, P., Li, D., Li, W.-H., Bugliani, M., Marchetti, P., et al. (2013) · Journal of Clinical Investigation · doi:10.1172/jci68459 · Cited by 210 · see citing works
Racial Disparities in Obesity Treatment
Byrd, A. S., Toth, A. T., & Stanford, F. C. (2018) · Current Obesity Reports · doi:10.1007/s13679-018-0301-3 · Cited by 204 · see citing works
β Cell Aging Markers Have Heterogeneous Distribution and Are Induced by Insulin Resistance
Aguayo-Mazzucato, C., van Haaren, M., Mruk, M., Lee, T. B., Crawford, C., Hollister-Lock, J., Sullivan, B. A., Johnson, J. W., Ebrahimi, A., Dreyfuss, J. M., et al. (2017) · Cell Metabolism · doi:10.1016/j.cmet.2017.03.015 · Cited by 198 · see citing works
Homologous and heterologous asynchronicity between identified α‐, β‐ and δ‐cells within intact islets of Langerhans in the mouse
Nadal, Á., Quesada, I., & Soria, B. (1999) · The Journal of Physiology · doi:10.1111/j.1469-7793.1999.0085z.x · Cited by 196 · see citing works
Connexin-36 Gap Junctions Regulate In Vivo First- and Second-Phase Insulin Secretion Dynamics and Glucose Tolerance in the Conscious Mouse
Head, W. S., Orseth, M. L., Nunemaker, C. S., Satin, L. S., Piston, D. W., & Benninger, R. K. P. (2012) · Diabetes · doi:10.2337/db11-1312 · Cited by 171 · see citing works
Cx36-Mediated Coupling Reduces β-Cell Heterogeneity, Confines the Stimulating Glucose Concentration Range, and Affects Insulin Release Kinetics
Speier, S., Gjinovci, A., Charollais, A., Meda, P., & Rupnik, M. (2007) · Diabetes · doi:10.2337/db06-0232 · Cited by 166 · see citing works
Gap junctions and other mechanisms of cell–cell communication regulate basal insulin secretion in the pancreatic islet
Benninger, R. K. P., Head, W. S., Zhang, M., Satin, L. S., & Piston, D. W. (2011) · The Journal of Physiology · doi:10.1113/jphysiol.2011.218909 · Cited by 165 · see citing works
Self-citation
Metabolic Stress and Compromised Identity of Pancreatic Beta Cells
Swisa, A., Gläser, B., & Dor, Y. (2017) · Frontiers in Genetics · doi:10.3389/fgene.2017.00021 · Cited by 163 · see citing works
The Beta Cell in Type 2 Diabetes
Christensen, A. A., & GANNON, M. A. (2019) · Current Diabetes Reports · doi:10.1007/s11892-019-1196-4 · Cited by 163 · see citing works
Leader β cells coordinate Ca2+ dynamics across pancreatic islets in vivo
Salem, V., Silva, L., Suba, K., Georgiadou, E., Gharavy, S. N. M., Akhtar, N., Martin-Alonso, A., Gaboriau, D. C. A., Rothery, S., Stylianides, T., et al. (2019) · Nature Metabolism · doi:10.1038/s42255-019-0075-2 · Cited by 159 · see citing works
Connexin 36 Controls Synchronization of Ca2+ Oscillations and Insulin Secretion in MIN6 Cells
Calabrese, A., Zhang, M., Serre‐Beinier, V., Caton, D., Mas, C., Satin, L. S., & Meda, P. (2003) · Diabetes · doi:10.2337/diabetes.52.2.417 · Cited by 143 · see citing works
The effects of graded levels of calorie restriction: I. impact of short term calorie and protein restriction on body composition in the C57BL/6 mouse
Mitchell, S. E., Tang, Z., Kerbois, C., Delville, C., Konstantopedos, P., Bruel, A., Derous, D., Green, C., Aspden, R. M., Goodyear, S. R., et al. (2015) · Oncotarget · doi:10.18632/oncotarget.4142 · Cited by 121 · see citing works
Glucose-Stimulated Calcium Dynamics in Islets of Langerhans in Acute Mouse Pancreas Tissue Slices
Stožer, A., Dolenšek, J., & Rupnik, M. S. (2013) · PLoS ONE · doi:10.1371/journal.pone.0054638 · Cited by 106 · see citing works
Spatially Organized β-Cell Subpopulations Control Electrical Dynamics across Islets of Langerhans.
Westacott, M. J., Ludin, N., & Benninger, R. (2017) · Biophysical Journal · doi:10.1016/j.bpj.2017.07.021 · Cited by 96 · see citing works
Metabolic mechanisms of failure of intraportally transplanted pancreatic beta-cells in rats: role of lipotoxicity and prevention by leptin.
Lee, Y., Ravazzola, M., Park, B., Bashmakov, Y., Orci, L., & Unger, R. (2007) · Diabetes · doi:10.2337/db07-0460 · Cited by 95 · see citing works
Connecting pancreatic islet lipid metabolism with insulin secretion and the development of type 2 diabetes
Imai, Y., Cousins, R. S., Liu, S., Phelps, B. M., & Promes, J. A. (2019) · Annals of the New York Academy of Sciences · doi:10.1111/nyas.14037 · Cited by 95 · see citing works
Insulin hypersecretion in islets from diet-induced hyperinsulinemic obese female mice is associated with several functional adaptations in individual β-cells.
González, A., Merino, B., Marroquí, L., Ñeco, P., Alonso-Magdalena, P., Caballero-Garrido, E., Vieira, E., Soriano, S., Gomis, R., Nadal, A., et al. (2013) · Endocrinology · doi:10.1210/en.2013-1424 · Cited by 92 · see citing works
Modulation of Autophagy Influences the Function and Survival of Human Pancreatic Beta Cells Under Endoplasmic Reticulum Stress Conditions and in Type 2 Diabetes
Bugliani, M., Mossuto, S., Grano, F., Suleiman, M., Marselli, L., Boggi, U., SIMONE, P. D., Eizirik, D. L., Cnop, M., Marchetti, P., et al. (2019) · Frontiers in Endocrinology · doi:10.3389/fendo.2019.00052 · Cited by 92 · see citing works
Fatty Acid-Stimulated Insulin Secretion vs. Lipotoxicity
Ježek, P., Jabůrek, M., Holendová, B., & Plecitá-Hlavatá, L. (2018) · Molecules · doi:10.3390/molecules23061483 · Cited by 78 · see citing works
Impaired β-cell-β-cell coupling mediated by Cx36 gap junctions in prediabetic mice
Carvalho, C. P. D. F., de Oliveira, R. B., Britan, A., Santos-Silva, J. C., Boschero, A. C., Meda, P., & Collares‐Buzato, C. B. (2012) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00489.2011 · Cited by 77 · see citing works
The Relationship between Membrane Potential and Calcium Dynamics in Glucose-Stimulated Beta Cell Syncytium in Acute Mouse Pancreas Tissue Slices
Dolenšek, J., Stožer, A., Klemen, M. S., Miller, E. W., & Rupnik, M. S. (2013) · PLoS ONE · doi:10.1371/journal.pone.0082374 · Cited by 72 · see citing works
Age-Dependent Decline in the Coordinated [Ca2+] and Insulin Secretory Dynamics in Human Pancreatic Islets
Westacott, M. J., Farnsworth, N. L., Clair, J. R. S., Poffenberger, G., Heintz, A., Ludin, N. W. F., Hart, N. J., Powers, A. C., & Benninger, R. K. P. (2017) · Diabetes · doi:10.2337/db17-0137 · Cited by 71 · see citing works
Pancreatic β-Cells From Mice Offset Age-Associated Mitochondrial Deficiency With Reduced KATP Channel Activity
Gregg, T., Poudel, C., Schmidt, B., Dhillon, R. S., Sdao, S. M., Truchan, N. A., Baar, E. L., Fernandez, L. A., Denu, J. M., Eliceiri, K. W., et al. (2016) · Diabetes · doi:10.2337/db16-0432 · Cited by 70 · see citing works
Disorganization of cytoplasmic Ca2+ oscillations and pulsatile insulin secretion in islets from ob/ob mice
Ravier, M., Sehlin, J., & Henquin, J. (2002) · Diabetologia · doi:10.1007/s00125-002-0883-9 · Cited by 59 · see citing works
Effects of caloric restriction on oxidative stress parameters
Stankovic, M. S., Mladenović, D. R., Ninković, M., Vučević, D. B., & Radosavljević, T. S. (2013) · General Physiology and Biophysics · doi:10.4149/gpb_2013027 · Cited by 59 · see citing works
Fluorescence recovery after photobleaching reveals regulation and distribution of connexin36 gap junction coupling within mouse islets of Langerhans
Farnsworth, N. L., Hemmati, A., Pozzoli, M., & Benninger, R. K. P. (2014) · The Journal of Physiology · doi:10.1113/jphysiol.2014.276733 · Cited by 57 · see citing works
Glucose represses connexin36 in insulin-secreting cells
Allagnat, F., Martin, D., Condorelli, D. F., Waeber, G., & Haefliger, J. (2005) · Journal of Cell Science · doi:10.1242/jcs.02600 · Cited by 57 · see citing works
Palmitate-induced lipotoxicity alters acetylation of multiple proteins in clonal β cells and human pancreatic islets
Ciregia, F., Bugliani, M., Ronci, M., Giusti, L., Boldrini, C., Mazzoni, M. R., Mossuto, S., Grano, F., Cnop, M., Marselli, L., et al. (2017) · Scientific Reports · doi:10.1038/s41598-017-13908-w · Cited by 57 · see citing works
β-cell metabolic alterations under chronic nutrient overload in rat and human islets
Vernier, S., Chiu, A., Schober, J. M., Weber, T., Nguyen, P., Luer, M. S., McPherson, T. B., Wanda, P. E., Marshall, C. A., Rohatgi, N., et al. (2012) · Islets · doi:10.4161/isl.22720 · Cited by 56 · see citing works
Enhanced glucose-induced intracellular signaling promotes insulin hypersecretion: Pancreatic beta-cell functional adaptations in a model of genetic obesity and prediabetes
Irles, E., Ñeco, P., Lluesma, M., Villar-Pazos, S., Santos-Silva, J. C., Vettorazzi, J. F., Alonso‐Magdalena, P., Carneiro, E. M., Boschero, A. C., Nadal, Á., et al. (2015) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2015.01.033 · Cited by 53 · see citing works
Moderate weight loss attenuates chronic endoplasmic reticulum stress and mitochondrial dysfunction in human obesity
López‐Domènech, S., Abad‐Jiménez, Z., Iannantuoni, F., Marañón, A., Rovira‐Llopis, S., Morillas, C., Bañuls, C., Víctor, V. M., & Rocha, M. (2018) · Molecular Metabolism · doi:10.1016/j.molmet.2018.10.005 · Cited by 53 · see citing works
The secretory deficit in islets from db/db mice is mainly due to a loss of responding beta cells
Do, O. H., Low, J. T., Gaisano, H. Y., & Thorn, P. (2014) · Diabetologia · doi:10.1007/s00125-014-3226-8 · Cited by 48 · see citing works
Differentiating the effects of Cx36 and E-cadherin for proper insulin secretion of MIN6 cells
Calabrese, A., Caton, D., & Meda, P. (2004) · Experimental Cell Research · doi:10.1016/j.yexcr.2003.12.007 · Cited by 48 · see citing works
Low Level Pro-inflammatory Cytokines Decrease Connexin36 Gap Junction Coupling in Mouse and Human Islets through Nitric Oxide-mediated Protein Kinase Cδ
Farnsworth, N. L., Walter, R. L., Hemmati, A., Westacott, M. J., & Benninger, R. K. P. (2016) · Journal of Biological Chemistry · doi:10.1074/jbc.m115.679506 · Cited by 48 · see citing works
Synchronous glucose‐dependent [Ca2+]i oscillations in mouse pancreatic islets of Langerhans recorded in vivo
Fernandez, J., & Valdeolmillos, M. (2000) · FEBS Letters · doi:10.1016/s0014-5793(00)01631-8 · Cited by 47 · see citing works
ICER-1γ Overexpression Drives Palmitate-mediated Connexin36 Down-regulation in Insulin-secreting Cells
Allagnat, F., Alonso, F., Martin, D., Abderrahmani, A., Waeber, G., & Haefliger, J. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m708181200 · Cited by 44 · see citing works
Defects in β-Cell Ca2+ Dynamics in Age-Induced Diabetes
Li, L., Trifunović, A., Köhler, M. G., Wang, Y., Berglund, J. P., Illies, C., Juntti‐Berggren, L., Larsson, N., & Berggren, P. (2014) · Diabetes · doi:10.2337/db13-1855 · Cited by 42 · see citing works
Combined lipidomic and proteomic analysis of isolated human islets exposed to palmitate reveals time-dependent changes in insulin secretion and lipid metabolism
Roomp, K., Kristinsson, H., Schvartz, D., Ubhayasekera, K. A., Sargsyan, E., Manukyan, L., Chowdhury, A. I., Manell, H., Satagopam, V., Groebe, K., et al. (2017) · PLoS ONE · doi:10.1371/journal.pone.0176391 · Cited by 41 · see citing works
Stress-induced dissociations between intracellular calcium signaling and insulin secretion in pancreatic islets
Qureshi, F. M., Dejene, E. A., Corbin, K. L., & Nunemaker, C. S. (2015) · Cell Calcium · doi:10.1016/j.ceca.2015.03.002 · Cited by 38 · see citing works
Metabolic consequence of long-term exposure of pancreatic β cells to free fatty acid with special reference to glucose insensitivity
Iizuka, K., Nakajima, H., Namba, M., Miyagawa, J.-I., Miyazaki, J., Hanafusa, T., & Matsuzawa, Y. (2002) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/s0925-4439(01)00082-5 · Cited by 37 · see citing works
Reversibility of β -Cell-Specific Transcript Factors Expression by Long-Term Caloric Restriction in db/db Mouse
Sheng, C., Li, F., Lin, Z., Zhang, M., Yang, P., Bu, L., Sheng, H., Li, H., & Qu, S. (2016) · Journal of Diabetes Research · doi:10.1155/2016/6035046 · Cited by 36 · see citing works
Dimensionality and Size Scaling of Coordinated Ca2+ Dynamics in MIN6 β-cell Clusters
Hraha, T. H., Bernard, A. B., Nguyen, L. M., Anseth, K. S., & Benninger, R. K. P. (2014) · Biophysical Journal · doi:10.1016/j.bpj.2013.11.026 · Cited by 35 · see citing works
β-Cell Control of Insulin Production During Starvation-Refeeding in Male Rats
Boland, B. B., Brown, C. L., Alarcón, C., Demozay, D., Grimsby, J. S., & Rhodes, C. J. (2017) · Endocrinology · doi:10.1210/en.2017-03120 · Cited by 34 · see citing works
Dietary restriction preserves the mass and function of pancreatic β cells via cell kinetic regulation and suppression of oxidative/ER stress in diabetic mice
Kanda, Y., Hashiramoto, M., Shimoda, M., Hamamoto, S., Tawaramoto, K., Kimura, T., Hirukawa, H., Nakashima, K., & Kaku, K. (2014) · The Journal of Nutritional Biochemistry · doi:10.1016/j.jnutbio.2014.10.007 · Cited by 33 · see citing works
The effect of different levels of dietary restriction on glucose homeostasis and metabolic memory
Matyi, S., Jackson, J. A., Garrett, K. P., Deepa, S. S., & Unnikrishnan, A. (2018) · GeroScience · doi:10.1007/s11357-018-0011-5 · Cited by 30 · see citing works
The In Vivo β-to-β-Cell Chat Room: Connexin Connections Matter
Meda, P. (2012) · Diabetes · doi:10.2337/db12-0336 · Cited by 29 · see citing works
The Lou/C rat: a model of spontaneous food restriction associated with improved insulin sensitivity and decreased lipid storage in adipose tissue
Veyrat‐Durebex, C., Montet, X., Vinciguerra, M., Gjinovci, A., Meda, P., Foti, M., & Rohner‐Jeanrenaud, F. (2009) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.90592.2008 · Cited by 29 · see citing works
In vivo Ca 2+ dynamics in single pancreatic β cells
Jacob, S., Köhler, M. G., Tröster, P., Visa, M., García‐Prieto, C. F., Alanentalo, T., Moede, T., Leibiger, B., Leibiger, I. B., & Berggren, P. (2019) · The FASEB Journal · doi:10.1096/fj.201901302rr · Cited by 27 · see citing works
Blocking Ca2+ Channel β3 Subunit Reverses Diabetes
Lee, K., Kim, J. J., Köhler, M. G., Yu, J. H., Shi, Y., Yang, S.-N., Ryu, S. H., & Berggren, P. (2018) · Cell Reports · doi:10.1016/j.celrep.2018.06.086 · Cited by 25 · see citing works
Short-term calorie restriction improves glucose homeostasis in old rats: involvement of AMPK
Pires, R. C., Souza, E. E., Vanzela, E. C., Ribeiro, R. A., Santos-Silva, J. C., Carneiro, E. M., Boschero, A. C., & do Amaral, M. E. C. (2014) · Applied Physiology, Nutrition, and Metabolism · doi:10.1139/apnm-2013-0520 · Cited by 24 · see citing works
Reduced expression of SIRT1 is associated with diminished glucose-induced insulin secretion in islets from calorie-restricted rats
do Amaral, M. E. C., Ueno, M., de Oliveira, C. A. M., Borsonello, N. C., Vanzela, E. C., Ribeiro, R. A., Alves, P. L., Barbosa, H. C. L., Carneiro, E. M., & Boschero, A. C. (2010) · The Journal of Nutritional Biochemistry · doi:10.1016/j.jnutbio.2010.04.010 · Cited by 24 · see citing works
Reduction of Connexin36 Content by ICER-1 Contributes to Insulin-Secreting Cells Apoptosis Induced by Oxidized LDL Particles
Haefliger, J., Martin, D. J., Favre, D., Petremand, Y., Mazzolai, L., Abderrahmani, A., Meda, P., Waeber, G., & Allagnat, F. (2013) · PLoS ONE · doi:10.1371/journal.pone.0055198 · Cited by 22 · see citing works
Metabolic effects of short-term caloric restriction in mice with reduced insulin gene dosage
Dommerholt, M. B., Dionne, D. A., Hutchinson, D., Kruit, J. K., & Johnson, J. D. (2018) · Journal of Endocrinology · doi:10.1530/joe-17-0505 · Cited by 21 · see citing works
Exendin‐4 overcomes cytokine‐induced decreases in gap junction coupling via protein kinase A and Epac2 in mouse and human islets
Farnsworth, N. L., Walter, R., Piscopio, R. A., Schleicher, W. E., & Benninger, R. K. P. (2018) · The Journal of Physiology · doi:10.1113/jp276106 · Cited by 21 · see citing works
Calorie Restriction from a Young Age Preserves the Functions of Pancreatic β Cells in Aging Rats
He, X., Zhao, X., Gu, Q., Shen, J., Hu, Y., & Hu, R. (2012) · The Tohoku Journal of Experimental Medicine · doi:10.1620/tjem.227.245 · Cited by 20 · see citing works
A Variant of GJD2, Encoding for Connexin 36, Alters the Function of Insulin Producing β-Cells
Cigliola, V., Populaire, C., Pierri, C. L., Deutsch, S., Haefliger, J., Fadista, J., Lyssenko, V., Groop, L., Rueedi, R., Thorel, F., et al. (2016) · PLoS ONE · doi:10.1371/journal.pone.0150880 · Cited by 20 · see citing works
Pancreatic islets from dexamethasone-treated rats show alterations in global gene expression and mitochondrial pathways
Roma, L. P., Souza, K. L. A., Carneiro, E. M., Boschero, A. C., & Bosqueiro, J. R. (2012) · General Physiology and Biophysics · doi:10.4149/gpb_2012_011 · Cited by 19 · see citing works
Chronic high fat feeding restricts islet mRNA translation initiation independently of ER stress via DNA damage and p53 activation
Hatanaka, M., Anderson‐Baucum, E. K., Lakhter, A. J., Kono, T., Maier, B., Tersey, S. A., Tanizawa, Y., Evans‐Molina, C., Mirmira, R. G., & Sims, E. K. (2017) · Scientific Reports · doi:10.1038/s41598-017-03869-5 · Cited by 19 · see citing works
Identification of early biological changes in palmitate-treated isolated human islets
Sargsyan, E., Cen, J., Roomp, K., Schneider, R., & Bergsten, P. (2018) · BMC Genomics · doi:10.1186/s12864-018-5008-z · Cited by 18 · see citing works
IKKβ inhibition prevents fat-induced beta cell dysfunction in vitro and in vivo in rodents
Ivovic, A., Oprescu, A. I., Koulajian, K., Mori, Y., Eversley, J. A., Zhang, L., Nino‐Fong, R., Lewis, G. F., Donath, M. Y., Karin, M., et al. (2017) · Diabetologia · doi:10.1007/s00125-017-4345-9 · Cited by 17 · see citing works
High‐fat‐diet‐induced remission of diabetes in a subset of K ATP ‐GOF insulin‐secretory‐deficient mice
Yan, Z., Shyr, Z. A., Fortunato, M., Welscher, A., Alisio, M., Martino, M. R., Finck, B. N., Conway, H., & Remedi, M. S. (2018) · Diabetes Obesity and Metabolism · doi:10.1111/dom.13423 · Cited by 8 · see citing works
Factors associated with progression to pre-diabetes: a recurrent events analysis
Mansourian, M., Yazdani, A., Faghihimani, E., Aminorroaya, A., Amini, M., & Jafari‐Koshki, T. (2018) · Eating and Weight Disorders - Studies on Anorexia Bulimia and Obesity · doi:10.1007/s40519-018-0529-7 · Cited by 7 · see citing works
Involvement of M1 and M3 receptors in isolated pancreatic islets function during weight cycling in ovariectomized rats
Pacher, K. A. S., Camargo, T. F., de Andrade, T. A. M., Barbosa, H. C. L., & do Amaral, M. E. C. (2019) · Biochemistry and Cell Biology · doi:10.1139/bcb-2018-0306 · Cited by 3 · see citing works

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The cardioprotective effects of semaglutide exceed those of dietary weight loss in mice with HFpEF
Withaar, C., Meems, L. M. G., Nollet, E. E., Schouten, E. M., Schroeder, M. A., Knudsen, L. B., Niss, K., Madsen, C. T., Hoegl, A., Mazzoni, G., et al. (2023) · JACC: Basic to Translational Science · doi:10.1016/j.jacbts.2023.05.012 · Cited by 74 · see citing works
The Role of cAMP in Beta Cell Stimulus–Secretion and Intercellular Coupling
Stožer, A., Leitgeb, E. P., Pohorec, V., Dolenšek, J., Bombek, L. K., Gosak, M., & Klemen, M. S. (2021) · Cells · doi:10.3390/cells10071658 · Cited by 64 · see citing works
“Along these lines, Cx36 gap junction coupling and its modulation are increasingly recognized as vital components in normal islet function [166168] and potentially viable targets to help restore insulin secretion in diabetes [169-171].”
Background
Redox Homeostasis in Pancreatic β-Cells: From Development to Failure
Benáková, Š., Holendová, B., & Plecitá‐Hlavatá, L. (2021) · Antioxidants · doi:10.3390/antiox10040526 · Cited by 55 · see citing works
“nization of calcium oscillations, and CX36-deficient mice show disrupted first-phase and pulsatile second phase of insulin release [234,235].”
Background
Glucose-dependent activation, activity, and deactivation of beta cell networks in acute mouse pancreas tissue slices
Stožer, A., Klemen, M. S., Gosak, M., Bombek, L. K., Pohorec, V., Rupnik, M. S., & Dolenšek, J. (2021) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00043.2021 · Cited by 45 · see citing works
Calorie restriction increases insulin sensitivity to promote beta cell homeostasis and longevity in mice
dos Santos, C., Cambraia, A., Shrestha, S., Cutler, M., Cottam, M. A., Perkins, G. A., Lev‐Ram, V., Roy, B., Acree, C., Keun-young Kim, A., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-53127-2 · Cited by 47 · see citing works
“…20 – 40% CR or CR achieved via TRF are linked to lower islet cell mass in lean mice 21 , whereas in pre-diabetic mice, CR restores normal beta cell secretory function, identity, and preserves beta cell mass 30 – 33 in a process dependent on activation of beta cell autophagy via Beclin-2 34 .”
BackgroundResult
Ca2+ Oscillations, Waves, and Networks in Islets From Human Donors With and Without Type 2 Diabetes
Gosak, M., Yan‐Do, R., Lin, H., MacDonald, P. E., & Stožer, A. (2022) · Diabetes · doi:10.2337/db22-0004 · Cited by 39 · see citing works
β-cell intrinsic dynamics rather than gap junction structure dictates subpopulations in the islet functional network
Briggs, J. K., Gresch, A., Marinelli, I., Dwulet, J. M., Albers, D. J., Kravets, V. V., & Benninger, R. K. P. (2023) · eLife · doi:10.7554/elife.83147 · Cited by 35 · see citing works
“…important in our understanding of islet dynamics in diabetes because both the gap junctions (e.g. the structural network) ( St. Clair et al., 2020 ; Corezola do Amaral et al., 2020 ; Farnsworth et al., 2022 ; Hodson et al., 2013 ; Carvalho et al., 2012 ; Farnsworth et al., 2016 ) and…”
BackgroundInfluential
Sirtuin function and metabolism: Role in pancreas, liver, and adipose tissue and their crosstalk impacting bone homeostasis
Avilkina, V., Chauveau, C., & Mhenni, O. G. (2021) · Bone · doi:10.1016/j.bone.2021.116232 · Cited by 32 · see citing works
From Isles of Königsberg to Islets of Langerhans: Examining the Function of the Endocrine Pancreas Through Network Science
Stožer, A., Sterk, M., Leitgeb, E. P., Markovič, R., Klemen, M. S., Ellis, C., Bombek, L. K., Dolenšek, J., Macdonald, P., & Gosak, M. (2022) · Frontiers in Endocrinology · doi:10.3389/fendo.2022.922640 · Cited by 28 · see citing works
Weight Cycling Impairs Pancreatic Insulin Secretion but Does Not Perturb Whole-Body Insulin Action in Mice With Diet-Induced Obesity
Winn, N. C., Cottam, M. A., Bhanot, M., Caslin, H. L., Garcia, J. N., Drigo, R. A. E., & Hasty, A. H. (2022) · Diabetes · doi:10.2337/db22-0161 · Cited by 28 · see citing works
Vertical sleeve gastrectomy triggers fast β-cell recovery upon overt diabetes
Oppenländer, L., Palit, S., Stemmer, K., Greisle, T., Sterr, M., Salinno, C., Bastidas-Ponce, A., Feuchtinger, A., Böttcher, A., Ansarullah, M., et al. (2021) · Molecular Metabolism · doi:10.1016/j.molmet.2021.101330 · Cited by 24 · see citing works
Exploring pancreatic beta-cell subgroups and their connectivity
Rutter, G. A., Gresch, A., Delgadillo-Silva, L. F., & Benninger, R. K. P. (2024) · Nature Metabolism · doi:10.1038/s42255-024-01097-6 · Cited by 24 · see citing works
Liraglutide increases islet Ca 2+ oscillation frequency and insulin secretion by activating hyperpolarization‐activated cyclic nucleotide‐gated channels
Zaborska, K. E., Jordan, K. L., Thorson, A. S., Dadi, P. K., Schaub, C. M., Nakhe, A. Y., Dickerson, M. T., Lynch, J. C., Weiss, A. J., Dobson, J. R., et al. (2022) · Diabetes Obesity and Metabolism · doi:10.1111/dom.14747 · Cited by 21 · see citing works
“from HFD-fed mice compared to control animals (Figure S11E); blunted and less coordinated islet Ca oscillations were also previously shown in mice exposed to prolonged HFD feeding.(42,43) Next,”
Background
Measurement of Pulsatile Insulin Secretion: Rationale and Methodology
LAURENTI, M. C., Matveyenko, A. V., & Vella, A. V. (2021) · Metabolites · doi:10.3390/metabo11070409 · Cited by 19 · see citing works
“At least in the early stages, these defects seem to be reversible [60,91,92].”
Background
Bariatric Surgery: Targeting pancreatic β cells to treat type II diabetes
Liu, T., Zou, X., Ruze, R., & Xu, Q. (2023) · Frontiers in Endocrinology · doi:10.3389/fendo.2023.1031610 · Cited by 22 · see citing works
A Critical Assessment of Fasting to Promote Metabolic Health and Longevity
Fazeli, P. K., & Steinhauser, M. L. (2025) · Endocrine Reviews · doi:10.1210/endrev/bnaf021 · Cited by 19 · see citing works
“…mechanisms may account for improved glucose homeostasis with fasting or caloric restriction, including improved β -cell survival or function (144, 145), improved skeletal muscle GLUT4 cell surface occupancy and responsiveness to insulin (55), and augmented mammalian target of rapamycin…”
Intra-islet glucagon signalling regulates beta-cell connectivity, first-phase insulin secretion and glucose homoeostasis
Suba, K., Patel, Y., Martin-Alonso, A., Hansen, B., Xu, X., Roberts, A. G., Norton, M., Chung, P., Shrewsbury, J. V., Kwok, R., et al. (2024) · Molecular Metabolism · doi:10.1016/j.molmet.2024.101947 · Cited by 18 · see citing works
Human Beta Cell Functional Adaptation and Dysfunction in Insulin Resistance and Its Reversibility
Klemen, M. S., Kopecký, J., Dolenšek, J., & Stožer, A. (2023) · The Nephron journals/Nephron journals · doi:10.1159/000534667 · Cited by 11 · see citing works
“…that is decreased in islets exposed to a diabetogenic environment in vivo or in vitro seems to be able to recover upon caloric restriction in mice [35] and at least in vitro and at least partially upon culture under normal conditions or by use of inhibitors of cytokine-mediated signaling pathways…”
Background
Network representation of multicellular activity in pancreatic islets: Technical considerations for functional connectivity analysis
Šterk, M., Zhang, Y., Pohorec, V., Leitgeb, E. P., Dolenšek, J., Benninger, R. K. P., Stožer, A., Kravets, V. V., & Gosak, M. (2024) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1012130 · Cited by 13 · see citing works
“Indeed, expression of Cx36 is decreased in diabetic conditions [47,48] leading to desynchronisation of [Ca 2+ ] i oscillations and perturbations in pulsatile insulin secretion [37,40,49–52].”
Background
The effect of forskolin and the role of Epac2A during activation, activity, and deactivation of beta cell networks
Klemen, M. S., Dolenšek, J., Bombek, L. K., Pohorec, V., Gosak, M., Rupnik, M. S., & Stožer, A. (2023) · Frontiers in Endocrinology · doi:10.3389/fendo.2023.1225486 · Cited by 12 · see citing works
Metabolic Alteration Bridging the Prediabetic State and Colorectal Cancer
Colloca, A., Donisi, I., Anastasio, C., Balestrieri, M. L., & D’Onofrio, N. (2024) · Cells · doi:10.3390/cells13080663 · Cited by 11 · see citing works
Is type 2 diabetes mellitus another intercellular junction-related disorder?
Collares‐Buzato, C. B., & Carvalho, C. P. D. F. (2022) · Experimental Biology and Medicine · doi:10.1177/15353702221090464 · Cited by 12 · see citing works
Restoring connexin‐36 function in diabetogenic environments precludes mouse and human islet dysfunction
Clair, J. R. S., Westacott, M. J., Miranda, J., Farnsworth, N. L., Kravets, V. V., Schleicher, W. E., Dwulet, J. M., Levitt, C. H., Heintz, A., Ludin, N. W. F., et al. (2023) · The Journal of Physiology · doi:10.1113/jp282114 · Cited by 10 · see citing works
“GJ coupling is diminished by conditions associated with diabetes, including by inflammatory cytokines, lipotoxic conditions, in animal models of diabetes and in aged human islets [37–39,51].”
BackgroundResultInfluential
Co‑expressed microRNAs, target genes and pathways related to metabolism, inflammation and endocrine function in individuals at risk for type 2 diabetes
Flowers, E., Asam, K. R., Allen, I. E., Kanaya, A. M., & Aouizerat, B. E. (2022) · Molecular Medicine Reports · doi:10.3892/mmr.2022.12672 · Cited by 9 · see citing works
“…T2d (40); notably, caloric restriction is one of the only known interventions to increase lifespan (41). animal model studies have provided evidence that caloric restriction improves β ‑cell function and decreases insulin resistance (42,43).”
The daily caloric restriction and alternate-day fasting ameliorated lipid dysregulation in type 2 diabetic mice by downregulating hepatic pescadillo 1
Zhou, J., Jiang, Z., Lin, Y., Li, C., Liu, J., Tian, M., Liu, Y., & Chen, K. (2022) · European Journal of Nutrition · doi:10.1007/s00394-022-02850-x · Cited by 9 · see citing works
“The two methods could improve several risk parameters of diabetes, including the reduced levels of fasting glucose and insulin, increased insulin sensitivity and improved lipid profiles [9, 10].”
BackgroundMethod
Concurrent Aerobic and Strength Training with Caloric Restriction Reduces Insulin Resistance in Obese Premenopausal Women: A Randomized Controlled Trial
Aneis, Y. M., Refaye, G. E. E., Taha, M. M., Aldhahi, M. I., & Elsisi, H. F. E. M. (2023) · Medicina · doi:10.3390/medicina59071193 · Cited by 8 · see citing works
Effects of fasting on skeletal muscles and body fat of adult and old C57BL/6J mice
Kvedaras, M., Minderis, P., Cesanelli, L., Čekanauskaitė, A., & Ratkevičius, A. (2021) · Experimental Gerontology · doi:10.1016/j.exger.2021.111474 · Cited by 7 · see citing works
Modulation of Gap Junction Coupling Within the Islet of Langerhans During the Development of Type 1 Diabetes
Farnsworth, N. L., Piscopio, R. A., Schleicher, W. E., Ramirez, D. G., Miranda, J. G., & Benninger, R. K. P. (2022) · Frontiers in Physiology · doi:10.3389/fphys.2022.913611 · Cited by 7 · see citing works
It’s What and When You Eat: An Overview of Transcriptional and Epigenetic Responses to Dietary Perturbations in Pancreatic Islets
Brown, M., & Matveyenko, A. V. (2022) · Frontiers in Endocrinology · doi:10.3389/fendo.2022.842603 · Cited by 6 · see citing works
Molecular Changes in Cells of Patients with Type 2 Diabetes Mellitus Depending on Changes in Glycemia Level in the Context of Lifestyle—An Overview of the Latest Scientific Discoveries
Szczechla, M., Balewska, A., Naskręt, D., Zozulińska‐Ziółkiewicz, D., & Uruska, A. A. (2023) · Current Issues in Molecular Biology · doi:10.3390/cimb45030126 · Cited by 6 · see citing works
““lipotoxicity can disrupt Cx36 gap junctions couplings within the islets in diet-induced obesity” [36] “decrease in insulin secretion and variability in glycemic homeostasis [36]”
BackgroundInfluential
Association Between Circulating Gremlin 2 and β‐Cell Function Among Participants With Prediabetes and Type 2 Diabetes
Ni, M., Chen, Y., Gu, W., Zhang, Y., Xu, M., Gu, Y., Chen, Y., Zhu, Y., Wang, X. D., Luo, Y., et al. (2025) · Journal of Diabetes · doi:10.1111/1753-0407.70090 · Cited by 4 · see citing works
Caloric restriction promotes beta cell longevity and delays aging and senescence by enhancing cell identity and homeostasis mechanismsPreprint
dos Santos, C., Shrestha, S., Cottam, M., Perkins, G., Lev-Ram, V., Roy, B., Acree, C., Kim, K., Deerinck, T., Cutler, M., et al. (2023) · bioRxiv · doi:10.1101/2023.08.23.554369 · Cited by 6 · see citing works
“…20-to-40% CR or CR achieved via TRF are linked to lower islet cell mass in lean mice 21 , whereas in pre-diabetic mice CR restores normal beta cell secretory function, identity, and preserves beta cell mass 30-33 in a process dependent on activation of beta cell autophagy via Beclin-2 34 .”
Diminished gap junction coupling under diabetogenic conditions does not drive loss of functional β-cell subpopulations
Levitt, C. H., Isaacs, D. P., Hansen, M. S., Kravets, V. V., Briggs, J. K., & Benninger, R. K. P. (2026) · The Journal of General Physiology · doi:10.1085/jgp.202513867 · Cited by 2 · see citing works
Application of Transmission Electron Microscopy to Detect Changes in Pancreas Physiology
Klemen, M. S., Dolenšek, J., Valladolid‐Acebes, I., Stožer, A., & Lipovšek, S. (2022) · IntechOpen eBooks · doi:10.5772/intechopen.104807 · Cited by 2 · see citing works
Caloric restriction prevents inflammation and insulin dysfunction in middle-aged ovariectomized mice
Sapatini, L. R. L., Calsa, B., Marim, L. J., Helaehil, J. V., Chiarotto, G. B., & do Amaral, M. E. C. (2023) · Molecular Biology Reports · doi:10.1007/s11033-023-08508-z · Cited by 2 · see citing works
The anti-aging mechanism of Berberine associated with metabolic control
Guo, X., Xiong, X., Lijun, Z., Zhong, G., & Zhu, X. (2023) · Elsevier eBooks · doi:10.1016/b978-0-12-823679-6.00020-5 · Cited by 1 · see citing works
Anti-Senescence Effect of Inhibiting Sodium-Glucose Cotransporter 2 and α-Glucosidase in a Type 2 Diabetes Mellitus Animal Model
Hong, S.-W., Kong, B. S., Lee, H., & Cho, Y. M. (2025) · Diabetes & Metabolism Journal · doi:10.4093/dmj.2024.0339 · Cited by 2 · see citing works
“Caloric restriction has been reported to be associated with reduced accumulation of senescent cells in the kidney, ovary, and heart [9] and has been shown to improve β-cell function in mice by recovering gap-junction connectivity [36] and restoring β-cell dedifferentiation [37].”
Detecting pre-desynchronized states in oscillatory systems
Ramírez, J. P., Sasahara, H., & Imura, J. (2023) · IFAC-PapersOnLine · doi:10.1016/j.ifacol.2023.10.673
Calorie Restriction Upregulates Islet PD-L1 Signaling and Decreases the Risk of Auto-immune Diabetes Onset in NOD MicePreprint
Cambraia, A., Schleh, M. W., Cartailler, J. P., Cutler, M., dos Santos, C., Many, G. M., Kim, H., Kim, Y., Nakayasu, E. S., Mogilenko, D. A., et al. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.02.15.705935
Communications intercellulaires dynamiques au sein des îlots pancréatiques analysées par multi-electrode arrays : rôles physiologiques et applications biotechnologiques en diabétologie
Jaffredo, M. (2021) · theses.fr (ABES) · doi:10.70675/00b154bazd615z4662zb0a0z275906108dbc
Calorie restriction modulates beta cell IP3R activity to regulate Ca2+ homeostasis and cell network connectivity
Pfabe, J. U., Cambraia, A., Dadi, P. K., Cutler, M., dos Santos, C., Acree, C., Habashy, A., Perkins, G. A., Ellisman, M. H., Jacobson, D. A., et al. (2026) · Cell Calcium · doi:10.1016/j.ceca.2026.103161 · Cited by 1 · see citing works

2076-P: Increased Gap Junction Coupling in the Islet of Langerhans following Caloric Restriction
AMARAL, M. C., Kravets, V. V., Dwulet, J. M., Farnsworth, N. L., Piscopio, R. A., Schleicher, W. E., MIRANDA, J., & Benninger, R. K. P. (2020) · Diabetes · doi:10.2337/db20-2076-p
Impaired β-cell-β-cell coupling mediated by Cx36 gap junctions in prediabetic mice
Carvalho, C. P. D. F., de Oliveira, R. B., Britan, A., Santos-Silva, J. C., Boschero, A. C., Meda, P., & Collares‐Buzato, C. B. (2012) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00489.2011 · Cited by 77 · see citing works
Restoring connexin‐36 function in diabetogenic environments precludes mouse and human islet dysfunction
Clair, J. R. S., Westacott, M. J., Miranda, J., Farnsworth, N. L., Kravets, V. V., Schleicher, W. E., Dwulet, J. M., Levitt, C. H., Heintz, A., Ludin, N. W. F., et al. (2023) · The Journal of Physiology · doi:10.1113/jp282114 · Cited by 10 · see citing works
Connexin-36 Gap Junctions Regulate In Vivo First- and Second-Phase Insulin Secretion Dynamics and Glucose Tolerance in the Conscious Mouse
Head, W. S., Orseth, M. L., Nunemaker, C. S., Satin, L. S., Piston, D. W., & Benninger, R. K. P. (2012) · Diabetes · doi:10.2337/db11-1312 · Cited by 171 · see citing works
Caloric restriction in obese pre-diabetic rats prevents beta-cell depletion, loss of beta-cell GLUT 2 and glucose incompetence
Ohneda, M., Inman, L. R., & Unger, R. H. (1995) · Diabetologia · doi:10.1007/bf00400091 · Cited by 110 · see citing works

Authors: Corezola do Amaral, M. E., Kravets, V., Dwulet, J. M., Farnsworth, N. L., Piscopio, R., Schleicher, W. E., Miranda, J. G., & Benninger, R. K. P.
Affiliations: Graduate Program in Biomedical Sciences, Centro Universitário da Fundação Hermínio Ometto, Araras, São Paulo, Brazil
University of Colorado Anschutz (US)
Corresponding author: Benninger, Richard K. P.
ORCID: Kravets, Vira
Dwulet, JaeAnn M.
Farnsworth, Nikki L.
Piscopio, Robert
Schleicher, Wolfgang E.
Benninger, Richard K. P.
Venue: American Journal of Physiology-Endocrinology and Metabolism
Publisher: American Physiological Society
Published: 2020-10-01
Volume: 319
Issue: 4
Pages: E709-E720
ISSN: 0193-1849 (ISSN-L)
1522-1555
DOI: 10.1152/ajpendo.00132.2020
PMC: PMC7750515
OpenAlex: W3081067659
Cited by: 41
References: 84
Citations by year: 2026: 3 · 2025: 3 · 2024: 5 · 2023: 12 · 2022: 10 · 2021: 8
FWCI: 6.85
Type: journal article
Language: en
Open access: green
doi.org
Locations: American Journal of Physiology-Endocrinology and Metabolism (publishedVersion)
bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: Fundacao de Amparo a Pesquisa do Estado de Sao Paolo (2018/04536-6)
NIH (R01 DK102950, R01 DK106412)
JDRF (5-CDA-2014-198-A-N)
Topics: Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Connexins and lens biology
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
Keywords: caloric restriction, prediabetes, connexin 36, electrical coupling, calcium oscillations, glucose-stimulated insulin secretion, islet dysfunction, high-fat diet, obesity, insulin resistance, glucose homeostasis, NAD(P)H autofluorescence, pancreatic islets
MeSH terms: Insulin Secretion, Gap Junction delta-2 Protein, Animals, Cell Communication, Insulin Resistance, Male, Mice, Inbred C57BL, Prediabetic State, Gap Junctions, Connexins, Calcium Signaling, Caloric Restriction, Insulin-Secreting Cells, Mice, Diet, High-Fat

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Caloric restriction recovers impaired β-cell-β-cell gap junction coupling, calcium oscillation coordination, and insulin secretion in prediabetic mice

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