Development of an optimized 5-stage protocol for the in vitro preparation of insulin-secreting cells from mouse ES cells

Saito, Mikako; Kaneda, Asako; Shigeto, Hajime; Hanata, Nobuaki; Otokuni, Keiko; Matsuoka, Hiroaki

doi:10.1007/s10616-015-9853-1

Cited by 6 publications

(2 citation statements)

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“…The threshold values between the normal and pre-diabetic conditions and the pre-diabetic and diabetic states could be determined based on the accumulated results of the glucose tolerance tests. Thus, the determined threshold value between the pre-diabetic and diabetic states was thought to be applicable as a quantitative standard in the risk assessment of diabetes (Saito et al 2016).…”

Section: Introductionmentioning

confidence: 99%

Functional role of natural killer T cells in non-obese pre-diabetes model mice

et al. 2017

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Pre-diabetic patients have a high risk of developing diabetes as well as other associated diseases. From the viewpoint of risk assessment and to assist the development of protective therapies, we focused on the functional role of natural killer T (NKT) cells in pre-diabetes. We found that the expression of an NKT cell marker gene, Va14-Ja18, was significantly lower in specific tissues/organs such as adipose tissue and pancreas in non-obese pre-diabetes model mice than in their normal littermates. Subsequently, in the pre-diabetes model mice, Va14-Ja18 was activated with α-galactosylceramide (α-GalCer) and its effect on glucose tolerance was estimated. The simultaneous injection of α-GalCer and lymphocytes improved glucose tolerance with its maximum effect on the 3rd day. An analysis of circulating cytokine levels revealed that interferon-γ, which is a pro-inflammatory cytokine, was secreted only on the 1st day after treatment with α-GalCer and that interleukin (IL)-4, which is an anti-inflammatory cytokine, was secreted from the 1st to the 4th day. The prolonged secretion of IL-4 was thought to substantially contribute to the improvement of glucose tolerance. Based on these results, the functional role of NKT cells in pre-diabetes is to improve metabolic dysfunctions.

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Section: Introductionmentioning

confidence: 99%

Functional role of natural killer T cells in non-obese pre-diabetes model mice

et al. 2017

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“…useful models for understanding the molecular mechanism [15][16][17]. In this way, after establishment of pancreatic endoderm, inhibition of Notch signaling leads to further endocrine differentiation and, subsequently, maturation of endocrine precursors toward specialized insulin-producing cells occurs [18].…”

Section: Introductionmentioning

confidence: 99%

The Role of Mesenchymal Stem Cells in Diabetes Mellitus

Azarpira¹

2015

Int J Stem Cell Res Ther

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RAGE is a critical factor of sex-based differences in age-induced kidney damage

Bajwa

Luebbe

et al. 2023

Front. Physiol.

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Introduction: Advanced glycation end products (AGEs) are a heterogeneous group of molecules with potential pathophysiological effects on the kidneys. Fibrosis together with the accumulation of AGEs has been investigated for its contribution to age-related decline in renal function. AGEs mediate their effects in large parts through their interactions with the receptor for AGEs (RAGE). RAGE is a transmembrane protein that belongs to the immunoglobulin superfamily and has the ability to interact with multiple pro-inflammatory/pro-oxidative ligands. The role of RAGE in aging kidneys has not been fully characterized, especially for sex-based differences.Methods: Therefore, we analyzed constitutive RAGE knockout (KO) mice in an age- and sex-dependent manner. Paraffin-embedded kidney sections were used for histological analysis and protein expression of fibrosis and damage markers. RNA expression analysis from the kidney cortex was done by qPCR for AGE receptors, kidney damage, and early inflammation/fibrosis factors. FACS analysis was used for immune cell profiling of the kidneys.Results: Histological analysis revealed enhanced infiltration of immune cells (positive for B220) in aged (>70 weeks old) KO mice in both sexes. FACS analysis revealed a similar pattern of enhanced B-1a cells in aged KO mice. There was an age-based increase in pro-fibrotic and pro-inflammatory markers (IL-6, TNF, TGF-β1, and SNAIL1) in KO male mice that presumably contributed to renal fibrosis and renal damage (glomerular and tubular). In fact, in KO mice, there was an age-dependent increase in renal damage (assessed by NGAL and KIM1) that was accompanied by increased fibrosis (assessed by CTGF). This effect was more pronounced in male KO mice than in the female KO mice. In contrast to the KO animals, no significant increase in damage markers was detectable in wild-type animals at the age examined (>70 weeks old). Moreover, there is an age-based increase in AGEs and scavenger receptor MSR-A2 in the kidneys.Discussion: Our data suggest that the loss of the clearance receptor RAGE in male animals further accelerates age-dependent renal damage; this could be in part due to an increase in AGEs load during aging and the absence of protective female hormones. By contrast, in females, RAGE expression seems to play only a minor role when compared to tissue pathology.

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Development of an optimized 5-stage protocol for the in vitro preparation of insulin-secreting cells from mouse ES cells

Cited by 6 publications

References 28 publications

Functional role of natural killer T cells in non-obese pre-diabetes model mice

Functional role of natural killer T cells in non-obese pre-diabetes model mice

The Role of Mesenchymal Stem Cells in Diabetes Mellitus

RAGE is a critical factor of sex-based differences in age-induced kidney damage

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