In vivo models of gestational and type 2 diabetes mellitus characterized by endocrine pancreas cell impairments

in Journal of Endocrinology
Authors:
Sandra K Szlapinski London, Ontario, Canada

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https://orcid.org/0000-0002-2698-7224
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David J Hill Diabetes, Endocrinology and Metabolism, Lawson Health Research Institute, London, Ontario, Canada
Physiology and Pharmacology, Western University, London, Ontario, Canada

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Correspondence should be addressed to S Szlapinski: sszlapin@uwo.ca

This paper forms part of a themed collection on Insulin Resistance and Type 2 Diabetes Mellitus. The Guest Editors for this collection were Matthias Blüher, Stefan Bornstein and Martin Haluzík.

DOI:
https://doi.org/10.1530/JOE-23-0317
Volume/Issue:
Volume 260: Issue 3
Article Type:
Review Article
Article ID:
e230317
Online Publication Date:
05 Feb 2024
Copyright:
© the author(s) 2024
Collections:
Insulin resistance and type 2 diabetes mellitus
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Insulin resistance contributes to the development of various diseases, including type 2 diabetes and gestational diabetes. Even though gestational diabetes is specific to pregnancy, it can result in long-term glucose intolerance and type 2 diabetes after delivery. Given the substantial health and economic burdens associated with diabetes, it is imperative to better understand the mechanisms leading to insulin resistance and type 2 diabetes so that treatments targeted at reversing symptoms can be developed. Considering that the endocrine cells of the pancreas (islets of Langerhans) largely contribute to the pathogenesis of diabetes (beta-cell insufficiency and dysfunction), the elucidation of the various mechanisms of endocrine cell plasticity is important to understand. By better defining these mechanisms, targeted therapeutics can be developed to reverse symptoms of beta-cell deficiency and insulin resistance in diabetes. Animal models play an important role in better understanding these mechanisms, as techniques for in vivo imaging of endocrine cells in the pancreas are limited. Therefore, this review article will discuss the available rodent models of gestational and type 2 diabetes that are characterized by endocrine cell impairments in the pancreas, discuss the models with a comparison to human diabetes, and explore the potential mechanisms of endocrine cell plasticity that contribute to these phenotypes, as these mechanisms could ultimately be used to reverse blood glucose dysregulation in diabetes.

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Print ISSN:
0022-0795
Online ISSN:
1479-6805
Copyright:
© the author(s) 2024
Article ID:
e230317
Article Type:
Review Article
Received Date:
08 Oct 2023
Accepted Date:
10 Jan 2024
Print Publication Date:
01 Mar 2024
Online Publication Date:
05 Feb 2024
Keywords:
type 2 diabetes mellitus; gestational diabetes mellitus; insulin resistance; beta cell; islet of Langerhans

  • Ahlqvist E, Storm P, Käräjämäki A, Martinell M, Dorkhan M, Carlsson A, Vikman P, Prasad RB, Mansour Aly DM, Almgren P, et al.2018 Novel Subgroups of adult onset diabetes and their association with outcomes: a data-driven cluster analysis of six variables. Lancet Diabetes and Endocrinology 6 361–369. (https://doi.org/10.1016/S2213-8587(1830051-2)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Alán L, Olejár T, Cahová M, Zelenka J, Berková Z, Smětáková M, Saudek F, Matěj R & & Ježek P 2015 Delta cell hyperplasia in adult Goto-Kakizaki (GK/MolTac) diabetic rats. Journal of Diabetes Research 2015 385395. (https://doi.org/10.1155/2015/385395)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Avrahami D, Wang YJ, Schug J, Feleke E, Gao L, Liu C, HPAP Consortium, Naji A, Glaser B & & Kaestner KH 2020 Single-cell transcriptomics of human islet ontogeny defines the molecular basis of β-cell dedifferentiation in T2D. Molecular Metabolism 42 101057. (https://doi.org/10.1016/j.molmet.2020.101057)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Baeyens L, Hindi S, Sorenson RL & & German MS 2016 β-cell adaptation in pregnancy. Diabetes, Obesity and Metabolism 18(Supplement 1) 63–70. (https://doi.org/10.1111/dom.12716)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Banerjee RR, Cyphert HA, Walker EM, Chakravarthy H, Peiris H, Gu X, Liu Y, Conrad E, Goodrich L, Stein RW, et al.2016 Gestational diabetes mellitus from inactivation of prolactin receptor and MafB in islet β-cells. Diabetes 65 2331–2341. (https://doi.org/10.2337/db15-1527)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Beamish CA, Strutt BJ, Arany EJ & & Hill DJ 2016 Insulin-positive, Glut2-low cells present within mouse pancreas exhibit lineage plasticity and are enriched within extra-islet endocrine cell clusters. Islets 8 65–82. (https://doi.org/10.1080/19382014.2016.1162367)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Beamish CA, Zhang L, Szlapinski SK, Strutt BJ & & Hill DJ 2017a An increase in immature β-cells lacking Glut2 precedes the expansion of β-cell mass in the pregnant mouse. PLoS One 12 e0182256. (https://doi.org/10.1371/journal.pone.0182256)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Beamish CA, Mehta S, Strutt BJ, Chakrabarti S, Hara M & & Hill DJ 2017b Decrease in Ins+Glut2LO β-cells with advancing age in mouse and human pancreas. Journal of Endocrinology 233 229–241. (https://doi.org/10.1530/JOE-16-0475)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Bonner-Weir S 2000 Islet growth and development in the adult. Journal of Molecular Endocrinology 24 297–302. (https://doi.org/10.1677/jme.0.0240297)

  • Bourne RRA, Stevens GA, White RA, Smith JL, Flaxman SR, Price H, Jonas JB, Keeffe J, Leasher J, Naidoo K, et al.2013 Causes of vision loss worldwide, 1990–2010: a systematic analysis. Lancet. Global Health 1 e339–e349. (https://doi.org/10.1016/S2214-109X(1370113-X)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Bramswig NC, Everett LJ, Schug J, Dorrell C, Liu C, Luo Y, Streeter PR, Naji A, Grompe M & & Kaestner KH 2013 Epigenomic plasticity enables human pancreatic α to β cell reprogramming. Journal of Clinical Investigation 123 1275–1284. (https://doi.org/10.1172/JCI66514)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Butler AE, Cao-Minh L, Galasso R, Rizza RA, Corradin A, Cobelli C & & Butler PC 2010 Adaptive changes in pancreatic beta cell fractional area and beta cell turnover in human pregnancy. Diabetologia 53 2167–2176. (https://doi.org/10.1007/s00125-010-1809-6)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Carril Pardo CA, Massoz L, Dupont MA, Bergemann D, Bourdouxhe J, Lavergne A, Tarifeño-Saldivia E, Helker CS, Stainier DY, Peers B, et al.2022 A δ-cell subpopulation with a pro-β-cell identity contributes to efficient age-independent recovery in a zebrafish model of diabetes. eLife 11 e67576. (https://doi.org/10.7554/eLife.67576)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Cerf ME 2013 Beta cell dysfunction and insulin resistance. Frontiers in Endocrinology 4 37. (https://doi.org/10.3389/fendo.2013.00037)

  • Chamson-Reig A, Thyssen SM, Arany E & & Hill DJ 2006 Altered pancreatic morphology in the offspring of pregnant rats given reduced dietary protein is time and gender specific. Journal of Endocrinology 191 83–92. (https://doi.org/10.1677/joe.1.06754)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Chamson-Reig A, Thyssen SM, Hill DJ & & Arany E 2009 Exposure of the pregnant rat to low protein diet causes impaired glucose homeostasis in the young adult offspring by different mechanisms in males and females. Experimental Biology and Medicine 234 1425–1436. (https://doi.org/10.3181/0902-RM-69)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Chen L, Huang X, Yang Y, Zhou M-j, Hao Z-f, Kong G-m, Hu R & & Bo P 2016 High fat diet combined with streptozotocin-induced gestational diabetes mellitus on mice. Chinese Journal of Comparative Medicine 26 15–18. (https://doi.org/10.3969.j.issn.1671-7856)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Chen Y, Jia J, Zhao Q, Zhang Y, Huang B, Wang L, Tian J, Huang C, Li M & & Li X 2022 Novel loss-of-function variant in HNF1a induces β-cell dysfunction through endoplasmic reticulum stress. International Journal of Molecular Sciences 23 13022. (https://doi.org/10.3390/ijms232113022)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Chera S, Baronnier D, Ghila L, Cigliola V, Jensen JN, Gu G, Furuyama K, Thorel F, Gribble FM, Reimann F, et al.2014 Diabetes recovery by age-dependent conversion of pancreatic δ-cells into insulin producers. Nature 514 503–507. (https://doi.org/10.1038/nature13633)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Chung JY, Ma Y, Zhang D, Bickerton HH, Stokes E, Patel SB, Tse HM, Feduska J, Welner RS & & Banerjee RR 2023 Pancreatic islet cell type–specific transcriptomic changes during pregnancy and postpartum. iScience 26 106439. (https://doi.org/10.1016/j.isci.2023.106439)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Costes S, Langen R, Gurlo T, Matveyenko AV & & Butler PC 2013 β-cell failure in type 2 diabetes: a case of asking too much of too few? Diabetes 62 327–335. (https://doi.org/10.2337/db12-1326)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Courty E, Besseiche A, Do TTH, Liboz A, Aguid FM, Quilichini E, Buscato M, Gourdy P, Gautier JF, Riveline JP, et al.2019 Adaptive β-cell neogenesis in the adult mouse in response to glucocorticoid-induced insulin resistance. Diabetes 68 95–108. (https://doi.org/10.2337/db17-1314)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Cox AR, Gottheil SK, Arany EJ & & Hill DJ 2010 The effects of low protein during gestation on mouse pancreatic development and beta cell regeneration. Pediatric Research 68 16–22. (https://doi.org/10.1203/PDR.0b013e3181e17c90)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Cui X, Feng J, Wei T, Gu L, Wang D, Lang S, Yang K, Yang J, Yan H, Wei R, et al.2022 Pro-α-cell-derived β-cells contribute to β-cell neogenesis induced by antagonistic glucagon receptor antibody in type 2 diabetic mice. iScience 25 104567. (https://doi.org/10.1016/j.isci.2022.104567)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Đorđević M, Stepper P, Feuerstein-Akgoz C, Gerhauser C, Paunović V, Tolić A, Rajić J, Dinić S, Uskoković A, Grdović N, et al.2023 EpiCRISPR targeted methylation of Arx gene initiates transient switch of mouse pancreatic alpha to insulin-producing cells. Frontiers in Endocrinology 14 1134478. (https://doi.org/10.3389/fendo.2023.1134478)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Emerging Risk Factors Collaboration, Sarwar N, Gao P, Seshasai SRK, Gobin R, Kaptoge S, Di Angelantonio E, Ingelsson E, Lawlor DA, Selvin E, et al.2010 Diabetes mellitus, fasting blood glucose concentration, and risk of vascular disease: a collaborative meta-analysis of 102 prospective studies. Lancet 375 2215–2222. (https://doi.org/10.1016/S0140-6736(1060484-9)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Endo A, Imai J, Izumi T, Kawana Y, Sugawara H, Kohata M, Seike J, Kubo H, Komamura H, Sato T, et al.2023 Phagocytosis by macrophages promotes pancreatic β cell mass reduction after parturition in mice. Developmental Cell 58 1819–1829.e5. (https://doi.org/10.1016/j.devcel.2023.08.002)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Fasoulakis Z, Koutras A, Antsaklis P, Theodora M, Valsamaki A, Daskalakis G & & Kontomanolis EN 2023 Intrauterine growth restriction due to gestational diabetes: from pathophysiology to diagnosis and management. Medicina (Kaunas) 59 1139. (https://doi.org/10.3390/medicina59061139)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Feldman H, ElSayed NA, McCoy RG, Moverley J, Oser SM, Segal AR, Trujillo J, Jones CW, Pilla SJ, Aung NL, et al.2023 Standards of care in diabetes—2023 abridged for primary care providers. Clinical Diabetes 41 4–31. (https://doi.org/10.2337/cd23-as01)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Fujita Y, Kozawa J, Fukui K, Iwahashi H, Eguchi H & & Shimomura I 2021 Increased NKX6.1 expression and decreased ARX expression in alpha cells accompany reduced beta-cell volume in human subjects. Scientific Reports 11 17796. (https://doi.org/10.1038/s41598-021-97235-1)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Furman BL 2015 Streptozotocin-induced diabetic models in mice and rats. Current Protocols in Pharmacology 70 5.47.1–5.47.20. (https://doi.org/10.1002/0471141755.ph0547s70)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Furth-Lavi J, Hija A, Tornovsky-Babeay S, Mazouz A, Dahan T, Stolovich-Rain M, Klochendler A, Dor Y, Avrahami D & & Glaser B 2022 Glycemic control releases regenerative potential of pancreatic beta cells blocked by severe hyperglycemia. Cell Reports 41 111719. (https://doi.org/10.1016/j.celrep.2022.111719)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Furuyama K, Chera S, van Gurp L, Oropeza D, Ghila L, Damond N, Vethe H, Paulo JA, Joosten AM, Berney T, et al.2019 Diabetes relief in mice by glucose-sensing insulin-secreting human α-cells. Nature 567 43–48. (https://doi.org/10.1038/s41586-019-0942-8)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Galvin SG, Kay RG, Foreman R, Larraufie P, Meek CL, Biggs E, Ravn P, Jermutus L, Reimann F & & Gribble FM 2021 The human and mouse islet peptidome: effects of obesity and Type 2 diabetes, and assessment of intraislet production of glucagon-like Peptide-1. Journal of Proteome Research 20 4507–4517. (https://doi.org/10.1021/acs.jproteome.1c00463)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Goyvaerts L, Schraenen A, Lemaire K, Veld PI, Smolders I, Maroteaux L & & Schuit F 2022 Normal pregnancy-induced islet beta cell proliferation in mouse models that are deficient in serotonin-signaling. International Journal of Molecular Sciences 23 15816. (https://doi.org/10.3390/ijms232415816)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Gu L, Cui X, Lang S, Wang H, Hong T & & Wei R 2019 Glucagon receptor antagonism increases mouse pancreatic δ-cell mass through cell proliferation and duct-derived neogenesis. Biochemical and Biophysical Research Communications 512 864–870. (https://doi.org/10.1016/j.bbrc.2019.03.148)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Guo S 2014 Insulin signaling, resistance, and the metabolic syndrome: insights from mouse models into disease mechanisms. Journal of Endocrinology 220 T1–T23. (https://doi.org/10.1530/JOE-13-0327)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Guo S, Dai C, Guo M, Taylor B, Harmon JS, Sander M, Robertson RP, Powers AC & & Stein R 2013 Inactivation of specific β cell transcription factors in type 2 diabetes. Journal of Clinical Investigation 123 3305–3316. (https://doi.org/10.1172/JCI65390)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Hakonen E, Ustinov J, Palgi J, Miettinen PJ & & Otonkoski T 2014 EGFR signaling promotes β-cell proliferation and survivin expression during pregnancy. PLoS One 9 e93651. (https://doi.org/10.1371/journal.pone.0093651)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Hariri N, Gougeon R & & Thibault L 2010 A highly saturated fat-rich diet is more obesogenic than diets with lower saturated fat content. Nutrition Research 30 632–643. (https://doi.org/10.1016/j.nutres.2010.09.003)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Huang C, Snider F & & Cross JC 2009 Prolactin receptor is required for normal glucose homeostasis and modulation of beta-cell mass during pregnancy. Endocrinology 150 1618–1626. (https://doi.org/10.1210/en.2008-1003)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Huang X, Li Y, Tong X, Wu Y, Zhang R, Sheng L, Xu J, Yu Z, Chen Z, Sun T, et al.2023 Increased circulating IL-32 is associated with placenta macrophage-derived IL-32 and gestational diabetes mellitus. Journal of Clinical Endocrinology and Metabolism. (https://doi.org/10.1210/clinem/dgad531)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Huising MO, Lee S & & van der Meulen T 2018 Evidence for a neogenic niche at the periphery of pancreatic islets. BioEssays 40 e1800119. (https://doi.org/10.1002/bies.201800119)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Hummel KP, Coleman DL & & Lane PW 1972 The influence of genetic background on expression of mutations at the diabetes locus in the mouse. I. C57BL-KsJ and C57BL-6J strains. Biochemical Genetics 7 1–13. (https://doi.org/10.1007/BF00487005)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Ignácio-Souza LM, Reis SR, Arantes VC, Botosso BL, Veloso RV, Ferreira F, Boschero AC, Carneiro EM, de Barros Reis MA & & Latorraca MQ 2013 Protein restriction in early life is associated with changes in insulin sensitivity and pancreatic β-cell function during pregnancy. British Journal of Nutrition 109 236–247. (https://doi.org/10.1017/S000711451200089X)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Jennings RE, Berry AA, Strutt JP, Gerrard DT & & Hanley NA 2015 Human pancreas development. Development 142 3126–3137. (https://doi.org/10.1242/dev.120063)

  • Kitamura YI, Kitamura T, Kruse JP, Raum JC, Stein R, Gu W & & Accili D 2005 FoxO1 protects against pancreatic beta cell failure through NeuroD and MafA induction. Cell Metabolism 2 153–163. (https://doi.org/10.1016/j.cmet.2005.08.004)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Kloppel G, Lohr M, Habich K, Oberholzer M & & Heitz PU 1985 Islet pathology and the pathogenesis of type 1 and type 2 diabetes mellitus revisited. Survey and Synthesis of Pathology Research 4 110–125. (https://doi.org/10.1159/000156969)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Kothegala L, Miranda C, Singh M, Krieger JP & & Gandasi NR 2023 Somatostatin containing δ-cell number is reduced in type-2 diabetes. International Journal of Molecular Sciences 24 3449. (https://doi.org/10.3390/ijms24043449)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Lee GH, Proenca R, Montez JM, Carroll KM, Darvishzadeh JG, Lee JI & & Friedman JM 1996 Abnormal splicing of the leptin receptor in diabetic mice. Nature 379 632–635. (https://doi.org/10.1038/379632a0)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Le May C, Chu K, Hu M, Ortega CS, Simpson ER, Korach KS, Tsai MJ & & Mauvais-Jarvis F 2006 Estrogens protect pancreatic beta-cells from apoptosis and prevent insulin-deficient diabetes mellitus in mice. PNAS 103 9232–9237. (https://doi.org/10.1073/pnas.0602956103)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Li Y, Cao X, Li LX, Brubaker PL, Edlund H & & Drucker DJ 2005 Beta-Cell Pdx1 expression is essential for the glucoregulatory, proliferative, and cytoprotective actions of glucagon-like peptide-1. Diabetes 54 482–491. (https://doi.org/10.2337/diabetes.54.2.482)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Li HY, Liu YX, Harvey L, Shafaeizadeh S, van der Beek EM & & Han W 2020 A mouse model of gestation-specific transient hyperglycemia for translational studies. Journal of Endocrinology 244 501–510. (https://doi.org/10.1530/JOE-19-0516)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Licholai JA, Nguyen KP, Fobbs WC, Schuster CJ, Ali MA & & Kravitz AV 2018 Why do mice overeat high-fat diets? How high-fat diet alters the regulation of daily caloric intake in mice. Obesity 26 1026–1033. (https://doi.org/10.1002/oby.22195)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Lieschke GJ & & Currie PD 2007 Animal models of human disease: zebrafish swim into view. Nature Reviews Genetics 8 353–367. (https://doi.org/10.1038/nrg2091)

  • Lindström P 2007 The physiology of obese-hyperglycemic mice [ob/ob mice]. Scientific World Journal 7 666–685. (https://doi.org/10.1100/tsw.2007.117)

  • Maioli TU, Gonçalves JL, Miranda MCG, Martins VD, Horta LS, Moreira TG, Godard ALB, Santiago AF & & Faria AMC 2016 High sugar and butter (HSB) diet induces obesity and metabolic syndrome with decrease in regulatory T cells in adipose tissue of mice. Inflammation Research 65 169–178. (https://doi.org/10.1007/s00011-015-0902-1)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Martínez MS, Manzano A, Olivar LC, Nava M, Salazar J, D’Marco L, Ortiz R, Chacín M, Guerrero-Wyss M, Cabrera de Bravo M, et al.2021 The role of the α cell in the pathogenesis of diabetes: a world beyond the mirror. International Journal of Molecular Sciences 22 9504. (https://doi.org/10.3390/ijms22179504)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • McIntyre HD, Catalano P, Zhang C, Desoye G, Mathiesen ER & & Damm P 2019 Gestational diabetes mellitus. Nature Reviews. Disease Primers 5 47. (https://doi.org/10.1038/s41572-019-0098-8)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Mezza T, Muscogiuri G, Sorice GP, Clemente G, Hu J, Pontecorvi A, Holst JJ, Giaccari A & & Kulkarni RN 2014 Insulin resistance alters islet morphology in nondiabetic humans. Diabetes 63 994–1007. (https://doi.org/10.2337/db13-1013)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Mittendorfer B, Patterson BW, Haire-Joshu D, Cahill AG, Cade WT, Stein RI & & Klein S 2023 Insulin sensitivity and β-cell function during early and late pregnancy in women with and without gestational diabetes mellitus. Diabetes Care 46 2147–2154. (https://doi.org/10.2337/dc22-1894)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Miura Y, Hayakawa A, Kikuchi S, Tsumoto H, Umezawa K, Chiba Y, Soejima Y, Sawabe M, Fukui K, Akimoto Y, et al.2019 Fumarate accumulation involved in renal diabetic fibrosis in Goto-Kakizaki rats. Archives of Biochemistry and Biophysics 678 108167. (https://doi.org/10.1016/j.abb.2019.108167)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Moon JH & & Jang HC 2022 Gestational diabetes mellitus: diagnostic approaches and maternal-offspring complications. Diabetes and Metabolism Journal 46 3–14. (https://doi.org/10.4093/dmj.2021.0335)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Moon JH, Kim H, Kim H, Park J, Choi W, Choi W, Hong HJ, Ro HJ, Jun S, Choi SH, et al.2020 Lactation improves pancreatic β cell mass and function through serotonin production. Science Translational Medicine 12 eaay0455. (https://doi.org/10.1126/scitranslmed.aay0455)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Mosser RE, Maulis MF, Moullé VS, Dunn JC, Carboneau BA, Arasi K, Pappan K, Poitout V & & Gannon M 2015 High-fat diet-induced β-cell proliferation occurs prior to insulin resistance in C57BL/6J male mice. American Journal of Physiology. Endocrinology and Metabolism 308 E573–E582. (https://doi.org/10.1152/ajpendo.00460.2014)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Murakami T, Fujimoto H & & Inagaki N 2021 Non-invasive beta-cell imaging: visualization, quantification, and beyond. Frontiers in Endocrinology 12 714348. (https://doi.org/10.3389/fendo.2021.714348)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Nakajima S, Hira T & & Hara H 2015 Postprandial glucagon-like peptide-1 secretion is increased during the progression of glucose intolerance and obesity in high-fat/high-sucrose diet-fed rats. British Journal of Nutrition 113 1477–1488. (https://doi.org/10.1017/S0007114515000550)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Newbern D & & Freemark M 2011 Placental hormones and the control of maternal metabolism and fetal growth. Current Opinion in Endocrinology, Diabetes, and Obesity 18 409–416. (https://doi.org/10.1097/MED.0b013e32834c800d)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Nimkulrat SD, Bernstein MN, Ni Z, Brown J, Kendziorski C & & Blum B 2021 The anna Karenina model of β-cell maturation in development and their dedifferentiation in type 1 and type 2 diabetes. Diabetes 70 2058–2066. (https://doi.org/10.2337/db21-0211)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Overi D, Carpino G, Moretti M, Franchitto A, Nevi L, Onori P, De Smaele E, Federici L, Santorelli D, Maroder M, et al.2022 Islet regeneration and pancreatic duct glands in human and experimental diabetes. Frontiers in Cell and Developmental Biology 10 814165. (https://doi.org/10.3389/fcell.2022.814165)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Ozawa H, Fukui K, Fujita Y, Ishibashi C, Yoneda S, Nammo T, Fujita S, Baden MY, Kimura T, Tokunaga A, et al.2023 Expansion of human alpha‐cell area is associated with a higher maximum body mass index before the onset of type 2 diabetes. Journal of Diabetes 15 277–282. (https://doi.org/10.1111/1753-0407.13370)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Paschou SA, Papadopoulou-Marketou N, Chrousos GP & & Kanaka-Gantenbein C 2018 On type 1 diabetes mellitus pathogenesis. Endocrine Connections 7 R38–R46. (https://doi.org/10.1530/EC-17-0347)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Plows JF, Stanley JL, Baker PN, Reynolds CM & & Vickers MH 2018 The pathophysiology of gestational diabetes mellitus. International Journal of Molecular Sciences 19 3342. (https://doi.org/10.3390/ijms19113342)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Portha B, Serradas P, Bailbe D, Suzuki K, Goto Y & & Giroix MH 1991 Beta-cell insensitivity to glucose in the GK rat, a spontaneous nonobese model for type II diabetes. Diabetes 40 486–491. (https://doi.org/10.2337/diab.40.4.486)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Pretorius M & & Huang C 2022 Beta-cell adaptation to pregnancy - role of calcium dynamics. Frontiers in Endocrinology 13 853876. (https://doi.org/10.3389/fendo.2022.853876)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Quesada-Candela C, Tudurí E, Marroquí L, Alonso-Magdalena P, Quesada I & & Nadal Á 2019 Morphological and functional adaptations of pancreatic alpha-cells during late pregnancy in the mouse. Metabolism: Clinical and Experimental 0 153963. (https://doi.org/10.1016/j.metabol.2019.153963)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Recena Aydos L, Aparecida do Amaral L, Serafim de Souza R, Jacobowski AC, Freitas dos Santos E & & Rodrigues Macedo ML 2019 Nonalcoholic fatty liver disease induced by high-fat diet in C57BL/6 models. Nutrients 11 3067. (https://doi.org/10.3390/nu11123067)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Reed MJ, Meszaros K, Entes LJ, Claypool MD, Pinkett JG, Gadbois TM & & Reaven GM 2000 A new rat model of type 2 diabetes: the fat-fed, streptozotocin-treated rat. Metabolism: Clinical and Experimental 49 1390–1394. (https://doi.org/10.1053/meta.2000.17721)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Retnakaran R, Ye C, Kramer CK, Hanley AJ, Connelly PW, Sermer M & & Zinman B 2023 Deteriorating beta cell function is the dominant determinant of progression from normal glucose tolerance to prediabetes/diabetes in young women following pregnancy. Diabetologia 66 2154–2163. (https://doi.org/10.1007/s00125-023-05994-5)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Rieck S & & Kaestner KH 2010 Expansion of β-cell mass in response to pregnancy. Trends in Endocrinology and Metabolism 21 151–158. (https://doi.org/10.1016/j.tem.2009.11.001)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Riveline JP, Baz B, Nguewa JL, Vidal-Trecan T, Ibrahim F, Boudou P, Vicaut E, Brac de la Perrière A, Fetita S, Bréant B, et al.2020 Exposure to glucocorticoids in the first part of fetal life is associated with insulin secretory defect in adult humans. Journal of Clinical Endocrinology and Metabolism 105 dgz145. (https://doi.org/10.1210/clinem/dgz145)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Rorsman P & & Huising MO 2018 The somatostatin-secreting pancreatic δ-cell in health and disease. Nature Reviews Endocrinology 14 404–414. (https://doi.org/10.1038/s41574-018-0020-6)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Rowan JA, Rush EC, Plank LD, Lu J, Obolonkin V, Coat S & & Hague WM 2018 Metformin in gestational diabetes: the offspring follow-up (MiG TOFU): body composition and metabolic outcomes at 7–9 years of age. BMJ Open Diabetes Research and Care 6 e000456. (https://doi.org/10.1136/bmjdrc-2017-000456)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Saikia M, Holter MM, Donahue LR, Lee IS, Zheng QC, Wise JL, Todero JE, Phuong DJ, Garibay D, Coch R, et al.2021 GLP-1 receptor signaling increases PCSK1 and β cell features in human α cells. JCI Insight 6 e141851. (https://doi.org/10.1172/jci.insight.141851)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Saisho Y, Butler AE, Manesso E, Elashoff D, Rizza RA & & Butler PC 2013 β-cell mass and turnover in humans: effects of obesity and aging. Diabetes Care 36 111–117. (https://doi.org/10.2337/dc12-0421)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Saran R, Li Y, Robinson B, Ayanian J, Balkrishnan R, Bragg-Gresham J, Chen JTL, Cope E, Gipson D, He K, et al.2015 US renal data system 2014 annual data report: epidemiology of kidney disease in the United States. American Journal of Kidney Diseases 66(Supplement 1) A7. (https://doi.org/10.1053/j.ajkd.2015.05.001)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Sarnobat D, Moffett RC, Ma J, Flatt PR, McClenaghan NH & & Tarasov AI 2023 Taurine rescues pancreatic β-cell stress by stimulating α-cell transdifferentiation. Biofactors 49 646–662. (https://doi.org/10.1002/biof.1938)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Sorenson RL & & Brelje TC 1997 Adaptation of islets of Langerhans to pregnancy: beta-cell growth, enhanced insulin secretion and the role of lactogenic hormones. Hormone and Metabolic Research 29 301–307. (https://doi.org/10.1055/s-2007-979040)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Spijker HS, Ravelli RBG, Mommaas-Kienhuis AM, van Apeldoorn AA, Engelse MA, Zaldumbide A, Bonner-Weir S, Rabelink TJ, Hoeben RC, Clevers H, et al.2013 Conversion of mature human β-cells into glucagon-producing α-cells. Diabetes 62 2471–2480. (https://doi.org/10.2337/db12-1001)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Szlapinski SK & & Hill DJ 2021 Metabolic adaptations to pregnancy in healthy and gestational diabetic pregnancies: the pancreas - placenta axis. Current Vascular Pharmacology 19 141–153. (https://doi.org/10.2174/1570161118666200320111209)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Szlapinski SK, King RT, Retta G, Yeo E, Strutt BJ & & Hill DJ 2019 A mouse model of gestational glucose intolerance through exposure to a low protein diet during fetal and neonatal development. Journal of Physiology 597 4237–4250. (https://doi.org/10.1113/JP277884)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Szlapinski SK, Botros AA, Donegan S, King RT, Retta G, Strutt BJ & & Hill DJ 2020 Altered pancreas remodeling following glucose intolerance in pregnancy in mice. Journal of Endocrinology 245 315–326. (https://doi.org/10.1530/JOE-20-0012)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Szlapinski SK, Bennett J, Strutt BJ & & Hill DJ 2021 Increased alpha and beta cell mass during mouse pregnancy is not dependent on transdifferentiation. Experimental Biology and Medicine 246 617–628. (https://doi.org/10.1177/1535370220972686)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Takahashi M, Ikemoto S & & Ezaki O 1999 Effect of the fat/carbohydrate ratio in the diet on obesity and oral glucose tolerance in C57BL/6J mice. Journal of Nutritional Science and Vitaminology 45 583–593. (https://doi.org/10.3177/jnsv.45.583)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Taschetto APD, Zimath PL, Silvério R, Dos Santos C, Boschero AC, Dos Santos GJ & & Rafacho A 2021 Reduced insulin sensitivity and increased β/α cell mass is associated with reduced hepatic insulin-degrading enzyme activity in pregnant rats. Life Sciences 277 119509. (https://doi.org/10.1016/j.lfs.2021.119509)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Thaweethai T, Soetan Z, James K, Florez JC & & Powe CE 2023 Distinct insulin physiology trajectories in euglycemic pregnancy and gestational diabetes mellitus. Diabetes Care 46 2137–2146. (https://doi.org/10.2337/dc22-2226)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Thorel F, Népote V, Avril I, Kohno K, Desgraz R, Chera S & & Herrera PL 2010 Conversion of adult pancreatic alpha-cells to beta-cells after extreme beta-cell loss. Nature 464 1149–1154. (https://doi.org/10.1038/nature08894)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Tokuyama Y, Sturis J, DePaoli AM, Takeda J, Stoffel M, Tang J, Sun X, Polonsky KS & & Bell GI 1995 Evolution of beta-cell dysfunction in the male Zucker diabetic fatty rat. Diabetes 44 1447–1457. (https://doi.org/10.2337/diab.44.12.1447)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Tomita T, Doull V, Pollock HG & & Krizsan D 1992 Pancreatic islets of obese hyperglycemic mice (ob/ob). Pancreas 7 367–375. (https://doi.org/10.1097/00006676-199205000-00015)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Van Assche FA, Aerts L & & De Prins F 1978 A morphological study of the endocrine pancreas in human pregnancy. British Journal of Obstetrics and Gynaecology 85 818–820. (https://doi.org/10.1111/j.1471-0528.1978.tb15835.x)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • van der Meulen T & & Huising MO 2015 Role of transcription factors in the transdifferentiation of pancreatic islet cells. Journal of Molecular Endocrinology 54 R103–R117. (https://doi.org/10.1530/JME-14-0290)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Vargas R, Martins IP, Matiusso CCI, Casagrande RA, Zara CB, Huppes de Souza AC, Horst WP, Sieklicki TC, Becker TCA, Lucredi NC, et al.2023 Protein restriction during lactation causes transgenerational metabolic dysfunction in adult rat offspring. Frontiers in Nutrition 10 1062116. (https://doi.org/10.3389/fnut.2022.1062116)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Vasavada RC, Garcia-Ocaña A, Zawalich WS, Sorenson RL, Dann P, Syed M, Ogren L, Talamantes F & & Stewart AF 2000 Targeted expression of placental lactogen in the beta cells of transgenic mice results in beta cell proliferation, islet mass augmentation, and hypoglycemia. Journal of Biological Chemistry 275 15399–15406. (https://doi.org/10.1074/jbc.275.20.15399)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Wang Z, York NW, Nichols CG & & Remedi MS 2014a Pancreatic β cell dedifferentiation in diabetes and redifferentiation following insulin therapy. Cell Metabolism 19 872–882. (https://doi.org/10.1016/j.cmet.2014.03.010)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Wang X, DuBois DC, Sukumaran S, Ayyar V, Jusko WJ & & Almon RR 2014b Variability in Zucker diabetic fatty rats: differences in disease progression in hyperglycemic and normoglycemic animals. Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy 7 531–541. (https://doi.org/10.2147/DMSO.S69891)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Wei R, Cui X, Feng J, Gu L, Lang S, Wei T, Yang J, Liu J, Le Y, Wang H, et al.2020 Dapagliflozin promotes beta cell regeneration by inducing pancreatic endocrine cell phenotype conversion in type 2 diabetic mice. Metabolism: Clinical and Experimental 111 154324. (https://doi.org/10.1016/j.metabol.2020.154324)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Westermark P, Andersson A & & Westermark GT 2011 Islet amyloid polypeptide, islet amyloid, and diabetes mellitus. Physiological Reviews 91 795–826. (https://doi.org/10.1152/physrev.00042.2009)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • WHO 2020 The Top 10 Causes of Death. WHO’s Global Health Estimates Fact Sheet. Geneva, Switzerland: World Health Organization. (available at: https://www.who.int/en/news-room/fact-sheets/detail/the-top-10-causes-of-death)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Wirth F, Heitz FD, Seeger C, Combaluzier I, Breu K, Denroche HC, Thevenet J, Osto M, Arosio P, Kerr-Conte J, et al.2023 A human antibody against pathologic IAPP aggregates protects beta cells in type 2 diabetes models. Nature Communications 14 6294. (https://doi.org/10.1038/s41467-023-41986-0)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Xiang AH 2023 Diabetes in pregnancy for mothers and offspring: reflection on 30 years of clinical and translational research: the 2022 Norbert Freinkel award lecture. Diabetes Care 46 482–489. (https://doi.org/10.2337/dci22-0055)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Yamashita H, Shao J, Qiao L, Pagliassotti M & & Friedman JE 2003 Effect of spontaneous gestational diabetes on fetal and postnatal hepatic insulin resistance in Leprdb/+ mice. Pediatric Research 53 411–418. (https://doi.org/10.1203/01.PDR.0000049667.58071.7D)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Yanowski E, Yacovzada NS, David E, Giladi A, Jaitin D, Farack L, Egozi A, Ben-Zvi D, Itzkovitz S, Amit I, et al.2022 Physically interacting beta-delta pairs in the regenerating pancreas revealed by single-cell sequencing. Molecular Metabolism 60 101467. (https://doi.org/10.1016/j.molmet.2022.101467)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Ye L, Robertson MA, Hesselson D, Stainier DYR & & Anderson RM 2015 Glucagon is essential for alpha cell transdifferentiation and beta cell neogenesis. Development 142 1407–1417. (https://doi.org/10.1242/dev.117911)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Ye R, Wang M, Wang QA, Spurgin SB, Wang ZV, Sun K & & Scherer PE 2016 Autonomous interconversion between adult pancreatic α-cells and β-cells after differential metabolic challenges. Molecular Metabolism 5 437–448. (https://doi.org/10.1016/j.molmet.2016.05.001)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Yeung RO, Retnakaran R, Savu A, Butalia S & & Kaul P 2023 Gestational diabetes: one size does not fit all-an observational study of maternal and neonatal outcomes by maternal glucose profile. Diabetic Medicine e15205. (https://doi.org/10.1111/dme.15205)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Yokomizo H, Inoguchi T, Sonoda N, Sakaki Y, Maeda Y, Inoue T, Hirata E, Takei R, Ikeda N, Fujii M, et al.2014 Maternal high-fat diet induces insulin resistance and deterioration of pancreatic β-cell function in adult offspring with sex differences in mice. American Journal of Physiology 306 E1163–E1175. (https://doi.org/10.1152/ajpendo.00688.2013)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Zeng H, Vaka VR, He X, Booz GW & & Chen JX 2015 High-fat diet induces cardiac remodelling and dysfunction: assessment of the role played by SIRT3 loss. Journal of Cellular and Molecular Medicine 19 1847–1856. (https://doi.org/10.1111/jcmm.12556)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Zhang Z, Hu Y, Xu N, Zhou W, Yang L, Chen R, Yang R, Sun J & & Chen H 2019 A new way for beta cell neogenesis: transdifferentiation from alpha cells induced by glucagon-like peptide 1. Journal of Diabetes Research 2019 2583047. (https://doi.org/10.1155/2019/2583047)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Zhang F, Song M, Chen L, Yang X, Li F, Yang Q, Duan C, Ling M, Lai X, Zhu X, et al.2020 Dietary supplementation of lauric acid alleviates the irregular estrous cycle and the impaired metabolism and thermogenesis in female mice fed with high-fat diet (HFD). Journal of Agricultural and Food Chemistry 68 12631–12640. (https://doi.org/10.1021/acs.jafc.0c05235)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Zhuang J, Ying H & & Wang D 2014 Study on the establishment of gestational diabetes mellitus rat model with low-dose streptozotocin. Program on Obstetrics and Gynecological 8 607–610.

    • PubMed
    • Search Google Scholar
    • Export Citation