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Citations to this article

Recovery from diabetes in mice by β cell regeneration
Tomer Nir, … , Douglas A. Melton, Yuval Dor
Tomer Nir, … , Douglas A. Melton, Yuval Dor
Published September 4, 2007
Citation Information: J Clin Invest. 2007;117(9):2553-2561. https://doi.org/10.1172/JCI32959.
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Research Article Article has an altmetric score of 8

Recovery from diabetes in mice by β cell regeneration

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Abstract

The mechanisms that regulate pancreatic β cell mass are poorly understood. While autoimmune and pharmacological destruction of insulin-producing β cells is often irreversible, adult β cell mass does fluctuate in response to physiological cues including pregnancy and insulin resistance. This plasticity points to the possibility of harnessing the regenerative capacity of the β cell to treat diabetes. We developed a transgenic mouse model to study the dynamics of β cell regeneration from a diabetic state. Following doxycycline administration, transgenic mice expressed diphtheria toxin in β cells, resulting in apoptosis of 70%–80% of β cells, destruction of islet architecture, and diabetes. Withdrawal of doxycycline resulted in a spontaneous normalization of blood glucose levels and islet architecture and a significant regeneration of β cell mass with no apparent toxicity of transient hyperglycemia. Lineage tracing analysis indicated that enhanced proliferation of surviving β cells played the major role in regeneration. Surprisingly, treatment with Sirolimus and Tacrolimus, immunosuppressants used in the Edmonton protocol for human islet transplantation, inhibited β cell regeneration and prevented the normalization of glucose homeostasis. These results suggest that regenerative therapy for type 1 diabetes may be achieved if autoimmunity is halted using regeneration-compatible drugs.

Authors

Tomer Nir, Douglas A. Melton, Yuval Dor

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Total citations by year

Year: 2025 2024 2023 2022 2021 2020 2019 2018 2017 2016 2015 2014 2013 2012 2011 2010 2009 2008 2007 Total
Citations: 3 13 4 7 8 9 6 9 6 22 22 26 20 21 33 26 25 19 1 280
Citation information
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Citations to this article in year 2009 (25)

Title and authors Publication Year
Blood glucose levels regulate pancreatic beta-cell proliferation during experimentally-induced and spontaneous autoimmune diabetes in mice
K Pechhold, K Koczwara, X Zhu, VS Harrison, G Walker, J Lee, DM Harlan
PloS one 2009
Pulmonary surfactant: an immunological perspective
ZC Chroneos, Z Sever-Chroneos, VL Shepherd
Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 2009
Pig embryonic pancreatic tissue as a source for transplantation in diabetes: transient treatment with anti-LFA1, anti-CD48, and FTY720 enables long-term graft maintenance in mice with only mild ongoing immunosuppression
D Tchorsh-Yutsis, G Hecht, A Aronovich, E Shezen, Y Klionsky, C Rosen, R Bitcover, S Eventov-Friedman, H Katchman, S Cohen, O Tal, O Milstein, H Yagita, BR Blazar, Y Reisner
Diabetes 2009
Minireview: Meeting the demand for insulin: molecular mechanisms of adaptive postnatal beta-cell mass expansion
MM Sachdeva, DA Stoffers
Molecular Endocrinology 2009
Human β-cell Precursors Mature Into Functional Insulin-producing Cells in an Immunoisolation Device: Implications for Diabetes Cell Therapies
SH Lee, E Hao, AY Savinov, I Geron, AY Strongin, P Itkin-Ansari
Transplantation 2009
Slow and steady is the key to β-cell replication
K Brennand, D Melton
Journal of Cellular and Molecular Medicine 2009
Growth factor control of pancreatic islet regeneration and function
A Assmann, C Hinault, RN Kulkarni
Pediatric Diabetes 2009
LKB1 Regulates Pancreatic β Cell Size, Polarity, and Function
Z Granot, A Swisa, J Magenheim, M Stolovich-Rain, W Fujimoto, E Manduchi, T Miki, JK Lennerz, CJ Stoeckert, O Meyuhas, S Seino, MA Permutt, H Piwnica-Worms, N Bardeesy, Y Dor
Cell Metabolism 2009
Immune tolerance induction by integrating innate and adaptive immune regulators
J Suzuki, C Ricordi, Z Chen
Cell transplantation 2009
Survey of the Human Pancreatic  -Cell G1/S Proteome Reveals a Potential Therapeutic Role for Cdk-6 and Cyclin D1 in Enhancing Human  -Cell Replication and Function In Vivo
N Fiaschi-Taesch, TA Bigatel, B Sicari, KK Takane, F Salim, S Velazquez-Garcia, G Harb, K Selk, I Cozar-Castellano, AF Stewart
Diabetes 2009
Current Advances and Travails in Islet Transplantation
DM Harlan, NS Kenyon, O Korsgren, BO Roep
Diabetes 2009
Expansion of beta-cell mass in response to pregnancy
S Rieck, KH Kaestner
Trends in endocrinology and metabolism: TEM 2009
Adaptive  -Cell Proliferation Is Severely Restricted With Advanced Age
MM Rankin, JA Kushner
Diabetes 2009
Rapamycin prevents and breaks the anti-CD3-induced tolerance in NOD mice
A Valle, T Jofra, A Stabilini, M Atkinson, MG Roncarolo, M Battaglia
Diabetes 2009
Islet Grafting and Imaging in a Bioengineered Intramuscular Space
P Witkowski, H Sondermeijer, MA Hardy, DC Woodland, K Lee, G Bhagat, K Witkowski, F See, A Rana, A Maffei, S Itescu, PE Harris
Transplantation 2009
Promotion of β-Cell Differentiation in Pancreatic Precursor Cells by Adult Islet Cells
W Chen, S Begum, L Opare-Addo, J Garyu, TF Gibson, AL Bothwell, VE Papaioannou, KC Herold
Endocrinology 2009
Islet Alone Versus Islet After Kidney Transplantation: Metabolic Outcomes and Islet Graft Survival
S Deng, JF Markmann, M Rickels, H Yeh, JI Kim, MM Lian, Y Gu, E Markmann, M Palanjian, CF Barker, A Naji
Transplantation 2009
Pancreatic islet transplantation
H Noguchi
World journal of gastrointestinal surgery 2009
P21cip-overexpression in the mouse beta cells leads to the improved recovery from streptozotocin-induced diabetes
J Yang, W Zhang, W Jiang, X Sun, Y Han, M Ding, Y Shi, H Deng
PloS one 2009
Embryonic stem cell transplantation correlates with endogenous neurogenin 3 expression and pancreas regeneration in streptozotocin-injured mice
M Kodama, K Tsukamoto, K Yoshida, K Aoki, S Kanegasaki, G Quinn
The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society 2009
Epithelial-mesenchymal transition in cells expanded in vitro from lineage-traced adult human pancreatic beta cells
HA Russ, P Ravassard, J Kerr-Conte, F Pattou, S Efrat
PloS one 2009
Counterpoint: Clinical Islet Transplantation: Not Ready for Prime Time
MH Khan, DM Harlan
Diabetes care 2009
Point: Steady Progress and Current Challenges in Clinical Islet Transplantation
D Mineo, A Pileggi, R Alejandro, C Ricordi
Diabetes care 2009
How to make β cells?
M Borowiak, DA Melton
Current Opinion in Cell Biology 2009
Pancreatic islet transplantation
ML Corrêa-Giannella, AS do Amaral
Diabetology & metabolic syndrome 2009

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