Modeling Maturity Onset Diabetes of the Young in Pluripotent Stem Cells: Challenges and Achievements

Braverman-Gross, Carmel; Benvenisty, Nissim

doi:10.3389/fendo.2021.622940

Cited by 4 publications

(2 citation statements)

References 68 publications

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“…There have been tremendous advances in the field of human genetics in the past 20 years that have given insights into the genetic contribution to diabetes mellitus. Monogenic forms of diabetes mellitus are the most straightforward scenario for personalized modelling 39 . Maturity-onset diabetes of the young (MODY) and neonatal diabetes mellitus (NDM) are the two main forms of monogenic diabetes mellitus 40 .…”

Section: Modelling Pancreas Developmentmentioning

confidence: 99%

Towards a better understanding of diabetes mellitus using organoid models

2023

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Our understanding of diabetes mellitus has benefited from a combination of clinical investigations and work in model organisms and cell lines. Organoid models for a wide range of tissues are emerging as an additional tool enabling the study of diabetes mellitus. The applications for organoid models include studying human pancreatic cell development, pancreatic physiology, the response of target organs to pancreatic hormones and how glucose toxicity can affect tissues such as the blood vessels, retina, kidney and nerves. Organoids can be derived from human tissue cells or pluripotent stem cells and enable the production of human cell assemblies mimicking human organs. Many organ mimics relevant to diabetes mellitus are already available, but only a few relevant studies have been performed. We discuss the models that have been developed for the pancreas, liver, kidney, nerves and vasculature, how they complement other models, and their limitations. In addition, as diabetes mellitus is a multi-organ disease, we highlight how a merger between the organoid and bioengineering fields will provide integrative models.

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Section: Modelling Pancreas Developmentmentioning

confidence: 99%

Towards a better understanding of diabetes mellitus using organoid models

2023

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“…Maturity-onset diabetes of the young (MODY) is a kind of rare genetic disorder, constituting 1–5% of all diabetes cases [ 1 , 2 ]. To date, fourteen subtypes of MODY have been identified, due to mutations of genes that encode transcription factors (e.g., HNF4A and HNF1A), enzymes (e.g., GCK and CEL), and other important molecules (e.g., INS and SUR1), involved in pancreatic cells function and metabolism [ 3 , 4 ]. Manifestations vary from the causal genes.…”

Section: Introductionmentioning

confidence: 99%

Quantitative profiling and diagnostic potential of one-carbon and central metabolism pools in MODY2 and T1DM

Liu,

Xie,

et al. 2023

Diabetol Metab Syndr

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Background Maturity-onset diabetes of the young type 2 (MODY2) is a rare genetic disorder characterized as mild fasting hyperglycemia with low risk of vascular complications caused by glucokinase gene mutation. This study aims to investigate metabolites alteration associated with MODY2, exploring possible mechanism underlying characteristic clinical manifestations and low cardiovascular risks of MODY2 and providing serum metabolite biomarkers to facilitating MODY2 diagnosis. Methods Fasting serum samples from MODY2, type 1 diabetes (T1DM) and healthy individuals were collected. By using targeted metabolomics via liquid chromatography–tandem mass spectrometry platform, we quantified the metabolites involved in tricarboxylic acid (TCA) cycle and one-carbon metabolism. Results Metabolomic profiling revealed significant difference of intermediates from central metabolism cycle, methionine cycle and several amino acids between MODY2 and T1DM groups. Among these, serum citrate, α-ketoglutaric acid, serine, glycine, glutamine and homocysteine were significantly elevated in MODY2 patients compared with T1DM patients; and compared with healthy subjects, malate and methionine levels were significantly increased in the two groups of diabetic patients. The correlation analysis with clinical indexes showed that α- ketoglutarate, serine, glycine, and glutamine were negatively correlated with blood glucose indicators including fasting blood glucose, HbA1c, and GA, while citrate was positively correlated with C-peptide. And homocysteine displayed positive correlation with HDL and negative with C-reactive protein, which shed light on the mechanism of mild symptoms and low risk of cardiovascular complications in MODY2 patients. A panel of 4 metabolites differentiated MODY2 from T1DM with AUC of 0.924, and a combination of clinical indices and metabolite also gained good diagnostic value with AUC 0.948. Conclusion In this research, we characterized the metabolite profiles of TCA cycle and one-carbon metabolism in MODY2 and T1DM and identified promising diagnostic biomarkers for MODY2. This study may provide novel insights into the pathogenesis and clinical manifestations of MODY2.

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Human-Induced Pluripotent Stem Cell–Based Models for Studying Sex-Specific Differences in Neurodegenerative Diseases

Kiris

2021

Advances in Experimental Medicine and Biology

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Modeling Maturity Onset Diabetes of the Young in Pluripotent Stem Cells: Challenges and Achievements

Cited by 4 publications

References 68 publications

Towards a better understanding of diabetes mellitus using organoid models

Towards a better understanding of diabetes mellitus using organoid models

Quantitative profiling and diagnostic potential of one-carbon and central metabolism pools in MODY2 and T1DM

Human-Induced Pluripotent Stem Cell–Based Models for Studying Sex-Specific Differences in Neurodegenerative Diseases

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