The natural history of insulin content in the pancreas of female and male non‐obese diabetic mouse: implications for trials of diabetes prevention in humans

Valorani, M. G.; Hawa, M.; Buckley, L. R.; Afeltra, Antonella; Cacciapaglia, Fabio; Pozzilli, Paolo

doi:10.1002/dmrr.463

Cited by 4 publications

(3 citation statements)

References 17 publications

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“…autoimmune disease in NOD mice. We confirmed that b cell death and leukocyte infiltration increased during diabetes progression in NOD mice aged 4-18 weeks (Figure 2a-c) as reported elsewhere [28,29]. Of note, treatment with the butanol fraction of B. pilosa inhibited b cell death and leukocyte infiltration in NOD mice aged from 4 to 18 weeks (Figure 2d-f).…”

Section: Resultssupporting

confidence: 91%

The distinct effects of a butanol fraction of Bidens pilosa plant extract on the development of Th1-mediated diabetes and Th2-mediated airway inflammation in mice

et al. 2005

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Bidens pilosa is claimed to be useful for immune or anti-inflammatory disorders; however, little scientific evidence has been published concerning its function. In this paper, immune disease mouse models were used to study the function of a butanol fraction of B.pilosa. We demonstrated treatment with the butanol fraction of B.pilosa ameliorated Th1 cell-mediated autoimmune diabetes in nonobese diabetic (NOD) mice but caused deterioration of Th2 cell-mediated airway inflammation induced by ovalbumin (OVA) in BALB/c mice. We next showed that Th2 cytokines (IL-4 and/or IL-5) increased but Th1 cytokine (IFN-gamma) decreased following injections with the butanol fraction of B.pilosa in both mouse strains. Accordingly, Th2 cytokine-regulated IgE production in mouse serum increased following treatment with this fraction. Finally, we found that the butanol fraction of B.pilosa inhibited Th1 cell differentiation but promoted Th2 cell differentiation. Taken together, the butanol fraction of B.pilosa has a dichotomous effect on helper T cell-mediated immune disorders, plausibly via modulation of T cell differentiation.

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Section: Resultssupporting

confidence: 91%

The distinct effects of a butanol fraction of Bidens pilosa plant extract on the development of Th1-mediated diabetes and Th2-mediated airway inflammation in mice

et al. 2005

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“…Although much has been learned about β-cell development and β-cell biology and function in vitro (using isolated pancreatic islets), studies designed to examine β-cell phenotype in vivo have suffered from technical limitations. For instance, currently available techniques to quantify pancreatic β-cell mass rely on laborious histomorphometric techniques ( 1 ) or on assumptions that β-cell mass correlates with β-cell function (stimulated C-peptide release) ( 2 ) or total pancreatic insulin content ( 3 , 4 ). Furthermore, quantifying the different endocrine islet cellular constituents by staining for the hormones produced (i.e., glucagon by α-cells, insulin by β-cells, somatostatin by δ-cells, and pancreatic polypeptide by PP-cells) has to date been challenging, relying again mostly on histomorphometry, and automated image processing setups typically allow only single-parameter analysis ( 5 , 6 ).…”

mentioning

confidence: 99%

Dynamic Changes in Pancreatic Endocrine Cell Abundance, Distribution, and Function in Antigen-Induced and Spontaneous Autoimmune Diabetes

et al. 2009

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OBJECTIVE-Insulin deficiency in type 1 diabetes and in rodent autoimmune diabetes models is caused by ␤-cell-specific killing by autoreactive T-cells. Less is known about ␤-cell numbers and phenotype remaining at diabetes onset and the fate of other pancreatic endocrine cellular constituents.RESEARCH DESIGN AND METHODS-We applied multicolor flow cytometry, confocal microscopy, and immunohistochemistry, supported by quantitative RT-PCR, to simultaneously track pancreatic endocrine cell frequencies and phenotypes during a T-cell-mediated ␤-cell-destructive process using two independent autoimmune diabetes models, an inducible autoantigen-specific model and the spontaneously diabetic NOD mouse. RESULTS-The proportion of pancreatic insulin-positive ␤-cellsto glucagon-positive ␣-cells was about 4:1 in nondiabetic mice. Islets isolated from newly diabetic mice exhibited the expected severe ␤-cell depletion accompanied by phenotypic ␤-cell changes (i.e., hypertrophy and degranulation), but they also revealed a substantial loss of ␣-cells, which was further confirmed by quantitative immunohistochemisty. While maintaining normal randomly timed serum glucagon levels, newly diabetic mice displayed an impaired glucagon secretory response to non-insulin-induced hypoglycemia.CONCLUSIONS-Systematically applying multicolor flow cytometry and immunohistochemistry to track declining ␤-cell numbers in recently diabetic mice revealed an altered endocrine cell composition that is consistent with a prominent and unexpected islet ␣-cell loss. These alterations were observed in induced and spontaneous autoimmune diabetes models, became apparent at diabetes onset, and differed markedly within islets compared with sub-islet-sized endocrine cell clusters and among pancreatic lobes. We propose that these changes are adaptive in nature, possibly fueled by worsening glycemia and regenerative processes.

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“…Pancreatic insulin content was measured by extraction of frozen whole organ powder in acidic ethanol as described [32] . Pancreatic acid–ethanol extracts were centrifuged at 3000 g for 15 min at 4 °C and supernatants were collected.…”

Section: Methodsmentioning

confidence: 99%

Adipose tissue (P)RR regulates insulin sensitivity, fat mass and body weight

Shamansurova

Tan

Ahmed

et al. 2016

Molecular Metabolism

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ObjectiveWe previously demonstrated that the handle-region peptide, a prorenin/renin receptor [(P)RR] blocker, reduces body weight and fat mass and may improve insulin sensitivity in high-fat fed mice. We hypothesized that knocking out the adipose tissue (P)RR gene would prevent weight gain and insulin resistance.MethodsAn adipose tissue-specific (P)RR knockout (KO) mouse was created by Cre-loxP technology using AP2-Cre recombinase mice. Because the (P)RR gene is located on the X chromosome, hemizygous males were complete KO and had a more pronounced phenotype on a normal diet (ND) diet compared to heterozygous KO females. Therefore, we challenged the female mice with a high-fat diet (HFD) to uncover certain phenotypes. Mice were maintained on either diet for 9 weeks.ResultsKO mice had lower body weights compared to wild-types (WT). Only hemizygous male KO mice presented with lower total fat mass, higher total lean mass as well as smaller adipocytes compared to WT mice. Although food intake was similar between genotypes, locomotor activity during the active period was increased in both male and female KO mice. Interestingly, only male KO mice had increased O2 consumption and CO2 production during the entire 24-hour period, suggesting an increased basal metabolic rate. Although glycemia during a glucose tolerance test was similar, KO males as well as HFD-fed females had lower plasma insulin and C-peptide levels compared to WT mice, suggesting improved insulin sensitivity. Remarkably, all KO animals exhibited higher circulating adiponectin levels, suggesting that this phenotype can occur even in the absence of a significant reduction in adipose tissue weight, as observed in females and, thus, may be a specific effect related to the (P)RR.Conclusions(P)RR may be an important therapeutic target for the treatment of obesity and its associated complications such as type 2 diabetes.

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The natural history of insulin content in the pancreas of female and male non‐obese diabetic mouse: implications for trials of diabetes prevention in humans

Cited by 4 publications

References 17 publications

The distinct effects of a butanol fraction of Bidens pilosa plant extract on the development of Th1-mediated diabetes and Th2-mediated airway inflammation in mice

The distinct effects of a butanol fraction of Bidens pilosa plant extract on the development of Th1-mediated diabetes and Th2-mediated airway inflammation in mice

Dynamic Changes in Pancreatic Endocrine Cell Abundance, Distribution, and Function in Antigen-Induced and Spontaneous Autoimmune Diabetes

Adipose tissue (P)RR regulates insulin sensitivity, fat mass and body weight

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