Diabetes Stem Cell TreatmentDiabetes Stem Cell Therapy

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  • Effects of fructose-induced metabolic syndrome on rat skeletal cells and tissue, and their responses to metformin treatment.
    Related Articles

    Effects of fructose-induced metabolic syndrome on rat skeletal cells and tissue, and their responses to metformin treatment.

    Diabetes Res Clin Pract. 2017 Apr;126:202-213

    Authors: Felice JI, Schurman L, McCarthy AD, Sedlinsky C, Aguirre JI, Cortizo AM

    Abstract
    AIMS: Deleterious effects of metabolic syndrome (MS) on bone are still controversial. In this study we evaluated the effects of a fructose-induced MS, and/or an oral treatment with metformin on the osteogenic potential of bone marrow mesenchymal stromal cells (MSC), as well as on bone formation and architecture.
    METHODS: 32 male 8week-old Wistar rats were assigned to four groups: control (C), control plus oral metformin (CM), rats receiving 10% fructose in drinking water (FRD), and FRD plus metformin (FRDM). Samples were collected to measure blood parameters, and to perform pQCT analysis and static and dynamic histomorphometry. MSC were isolated to determine their osteogenic potential.
    RESULTS: Metformin improved blood parameters in FRDM rats. pQCT and static and dynamic histomorphometry showed no significant differences in trabecular and cortical bone parameters among groups. FRD reduced TRAP expression and osteocyte density in trabecular bone and metformin only normalized osteocyte density. FRD decreased the osteogenic potential of MSC and metformin administration could revert some of these parameters.
    CONCLUSIONS: FRD-induced MS shows reduction in MSC osteogenic potential, in osteocyte density and in TRAP activity. Oral metformin treatment was able to prevent trabecular osteocyte loss and the reduction in extracellular mineralization induced by FRD-induced MS.

    PMID: 28259010 [PubMed - indexed for MEDLINE]

  • Beige Adipocyte Maintenance Is Regulated by Autophagy-Induced Mitochondrial Clearance.
    Related Articles

    Beige Adipocyte Maintenance Is Regulated by Autophagy-Induced Mitochondrial Clearance.

    Cell Metab. 2016 Sep 13;24(3):402-19

    Authors: Altshuler-Keylin S, Shinoda K, Hasegawa Y, Ikeda K, Hong H, Kang Q, Yang Y, Perera RM, Debnath J, Kajimura S

    Abstract
    Beige adipocytes gained much attention as an alternative cellular target in anti-obesity therapy. While recent studies have identified a number of regulatory circuits that promote beige adipocyte differentiation, the molecular basis of beige adipocyte maintenance remains unknown. Here, we demonstrate that beige adipocytes progressively lose their morphological and molecular characteristics after withdrawing external stimuli and directly acquire white-like characteristics bypassing an intermediate precursor stage. The beige-to-white adipocyte transition is tightly coupled to a decrease in mitochondria, increase in autophagy, and activation of MiT/TFE transcription factor-mediated lysosome biogenesis. The autophagy pathway is crucial for mitochondrial clearance during the transition; inhibiting autophagy by uncoupled protein 1 (UCP1(+))-adipocyte-specific deletion of Atg5 or Atg12 prevents beige adipocyte loss after withdrawing external stimuli, maintaining high thermogenic capacity and protecting against diet-induced obesity and insulin resistance. The present study uncovers a fundamental mechanism by which autophagy-mediated mitochondrial clearance controls beige adipocyte maintenance, thereby providing new opportunities to counteract obesity.

    PMID: 27568548 [PubMed - indexed for MEDLINE]

pubmed: diabetes and stem ce...
NCBI: db=pubmed; Term=diabetes and stem cell treatment
NCBI pubmed
  • Effects of fructose-induced metabolic syndrome on rat skeletal cells and tissue, and their responses to metformin treatment.
    Related Articles

    Effects of fructose-induced metabolic syndrome on rat skeletal cells and tissue, and their responses to metformin treatment.

    Diabetes Res Clin Pract. 2017 Apr;126:202-213

    Authors: Felice JI, Schurman L, McCarthy AD, Sedlinsky C, Aguirre JI, Cortizo AM

    Abstract
    AIMS: Deleterious effects of metabolic syndrome (MS) on bone are still controversial. In this study we evaluated the effects of a fructose-induced MS, and/or an oral treatment with metformin on the osteogenic potential of bone marrow mesenchymal stromal cells (MSC), as well as on bone formation and architecture.
    METHODS: 32 male 8week-old Wistar rats were assigned to four groups: control (C), control plus oral metformin (CM), rats receiving 10% fructose in drinking water (FRD), and FRD plus metformin (FRDM). Samples were collected to measure blood parameters, and to perform pQCT analysis and static and dynamic histomorphometry. MSC were isolated to determine their osteogenic potential.
    RESULTS: Metformin improved blood parameters in FRDM rats. pQCT and static and dynamic histomorphometry showed no significant differences in trabecular and cortical bone parameters among groups. FRD reduced TRAP expression and osteocyte density in trabecular bone and metformin only normalized osteocyte density. FRD decreased the osteogenic potential of MSC and metformin administration could revert some of these parameters.
    CONCLUSIONS: FRD-induced MS shows reduction in MSC osteogenic potential, in osteocyte density and in TRAP activity. Oral metformin treatment was able to prevent trabecular osteocyte loss and the reduction in extracellular mineralization induced by FRD-induced MS.

    PMID: 28259010 [PubMed - indexed for MEDLINE]

  • Beige Adipocyte Maintenance Is Regulated by Autophagy-Induced Mitochondrial Clearance.
    Related Articles

    Beige Adipocyte Maintenance Is Regulated by Autophagy-Induced Mitochondrial Clearance.

    Cell Metab. 2016 Sep 13;24(3):402-19

    Authors: Altshuler-Keylin S, Shinoda K, Hasegawa Y, Ikeda K, Hong H, Kang Q, Yang Y, Perera RM, Debnath J, Kajimura S

    Abstract
    Beige adipocytes gained much attention as an alternative cellular target in anti-obesity therapy. While recent studies have identified a number of regulatory circuits that promote beige adipocyte differentiation, the molecular basis of beige adipocyte maintenance remains unknown. Here, we demonstrate that beige adipocytes progressively lose their morphological and molecular characteristics after withdrawing external stimuli and directly acquire white-like characteristics bypassing an intermediate precursor stage. The beige-to-white adipocyte transition is tightly coupled to a decrease in mitochondria, increase in autophagy, and activation of MiT/TFE transcription factor-mediated lysosome biogenesis. The autophagy pathway is crucial for mitochondrial clearance during the transition; inhibiting autophagy by uncoupled protein 1 (UCP1(+))-adipocyte-specific deletion of Atg5 or Atg12 prevents beige adipocyte loss after withdrawing external stimuli, maintaining high thermogenic capacity and protecting against diet-induced obesity and insulin resistance. The present study uncovers a fundamental mechanism by which autophagy-mediated mitochondrial clearance controls beige adipocyte maintenance, thereby providing new opportunities to counteract obesity.

    PMID: 27568548 [PubMed - indexed for MEDLINE]

  • Interferon-alpha inhibits adipogenesis via regulation of JAK/STAT1 signaling.
    Related Articles

    Interferon-alpha inhibits adipogenesis via regulation of JAK/STAT1 signaling.

    Biochim Biophys Acta. 2016 11;1860(11 Pt A):2416-27

    Authors: Lee K, Um SH, Rhee DK, Pyo S

    Abstract
    BACKGROUND INFORMATION: Adipose tissue regulates energy metabolism by means of adipocyte hypertrophy and/or the differentiation of pre-existing adipocytes. Excessive production of some cytokines in adipose tissue is known to be a negative regulator of adipocyte differentiation, and the resulting impaired adipogenesis contributes to disorders like insulin resistance. IFN-α is a key immunoregulatory cytokine in the development of type 1 diabetes, lipid disorders and insulin resistance; however, its effect on adipogenesis remains unknown.
    METHOD: We examined the effect of IFN-α on adipocyte differentiation and its mechanisms. The effect of IFN-α on adipogenesis was evaluated by Western blotting, qRT-PCR, flow cytometric analysis and Oil Red O staining. We also investigated the role of STAT1 in adipogenesis using gene silencing analysis.
    RESULTS: IFN-α inhibited the accumulation of lipid droplets and the expression of adipogenesis related genes. The inhibition of adipocyte differentiation by IFN-α occurred in the early stages of differentiation. IFN-α arrested the cell cycle at the G0/G1 phase and regulated the expression of CDK2 and p21. These results were confirmed in MEF cells. Treatment with IFN-α increased STAT1 phosphorylation, and STAT1 siRNA or inhibitor prevented IFN-α from inhibiting the expression of PPARγ and C/EBPα as well as cell cycle progression in 3T3-L1 cells.
    CONCLUSION: We suggest that IFN-α inhibits adipocyte differentiation during the early stage of adipogenesis by regulating the expression of PPARγ and C/EBPα as well as the cell cycle through JAK/STAT1 signaling pathways.
    GENERAL SIGNIFICANCE: Our study provides new insights into possible mechanisms of the anti-adipogenetic effects of IFN-α.

    PMID: 27424923 [PubMed - indexed for MEDLINE]