106 ADAPTIVE β-CELL EXPANSION IN PREGNANT MICE WITHOUT FETUSES

2014 ◽  
Vol 26 (1) ◽  
pp. 167
Author(s):  
S. Zhang ◽  
X. M. Zhang ◽  
Z. Y. Li
Keyword(s):  
Fluorescence Intensity ◽  
Insulin Level ◽  
Control Group ◽  
Cell Replication ◽  
Replication Rate ◽  
Β Cells ◽  
Β Cell ◽  
Significant Difference ◽  
Pregnant Mice ◽  
Physiological Demands

Diabetes, an increasingly prevalent metabolic disorder, which is estimated to affect over 300 million people by 2025 (Zimmet et al. 2001 Nature), commonly results from β-cell function failure. In normal physiological conditions, β-cell turnover occurs slowly throughout the lifetime of the adult mammal. During pregnancy, β cells could increase their replication rate through reducing menin expression and then cause islets hyperplasia to match the physiological demands (Karnik et al. 2007 Science). However, whether the fetuses have an influence on the β-cell replication and islets hyperplasia during pregnancy is still unknown. The objective of the present study was to test whether pregnancy without fetuses could also decrease the expression of menin, and then cause an increase in the β-cell replication rate and islets hyperplasia. First, we generated pregnant mice with tetraploid blastocysts (PT mice), which can implant and generate placentas similar to the normal diploid blastocysts, but cannot develop into fetuses. Pancreases from at least 3 mice per group were embedded in optimum cutting temperature compound (OCT) and sectioned at 8-μm intervals. The sections were stained with hematoxylin and eosin (HE), and then the morphological structures of islets were observed under a microscope. The results showed that the islets mass of PT mice had obvious hyperplasia compared with wild-type controls (WT). Second, we isolated the islets of PT mice, and analysed the Men1, p18, and p27 gene expression in PT mice islets using RT-PCR. We found that the expression of Men1, p27, and p18 in PT mice islets was significantly lower compared with WT controls (P < 0.05). Finally, insulin immunofluorescence was performed to evaluate the insulin expression level of β cells in the islets both from PT mice and the WT group. The evaluation of total fluorescence intensity in islets was performed. The average value from the control group islets was set to 1 and used for comparison to the fluorescence intensity of PT mice islets. The results showed that there was no significant difference between PT mice and WT groups at the insulin level of β cells. Taken together, these results demonstrate that under the conditions of pregnancy without fetuses, maternal pancreatic islets can also cause islets mass hyperplasia through reducing menin expression, but not increase the insulin level per β cell to match the dynamic physiological demands. Therefore, it's possible to treat type-2 diabetes by imitating the pregnant physiological condition without fetuses. This work was supported by grants from the National Natural Science Foundation (No. 31271591) and the National Basic Research Program (No. 2009CB941001 and No. 2011CBA01003) in China.

β Cell Protecting and Immunomodulatory Activities of Paecilomyces Hepiali Chen Mycelium in STZ Induced T1DM Mice

2009 ◽  
Vol 37 (02) ◽  
pp. 361-372 ◽  
Author(s):  
Ming Xiang ◽  
Jing Tang ◽  
Xiao-Lei Zou ◽  
Zeng-Yu Zhao ◽  
Yun-Yang Wang ◽  
...  
Keyword(s):  
Blood Glucose ◽  
Insulin Level ◽  
Inflammatory Cells ◽  
Diabetic Control ◽  
Control Group ◽  
Β Cells ◽  
Β Cell ◽  
Diabetic Control Group ◽  
Paecilomyces Hepiali

The anti-hyperglycemic and immunomodulatory activities of the ethanol extract from Paecilomyces Hepiali Chen (PHC), a Chinese medicine, were investigated in streptozotocin-induced type 1 diabetic (T1DM) mice. Male Balb/c mice, which were i.p. injected with streptozotocin (STZ, 50 mg/kg, for 5 consecutive days) on Day 7, were orally administered saline (the normal control and diabetic control group), Metformin (60 mg/kg, b.w., positive group), or the extract (100 mg/kg, b.w., PHC prevention group) from Day 1 to Day 28, Mice i.p. injected with streptozotocin (STZ, 50 mg/kg, b.w.) for 5 consecutive days prior to PHC treatment (100 mg/kg, b.w.) were used as the PHC treatment group. The effects of PHC on postprandial blood glucose concentrations, plasmatic insulin levels, morphology of pancreatic β cells and CD4+ T cells proliferation after 28-day treatment were monitored. Results showed that PHC administered 6 days before STZ induction of diabetes in mice significantly decreased blood glucose level (p < 0.01). An increase of insulin level was also observed as compared to those in the diabetic control group (p < 0.01). In addition, fewer inflammatory cells infiltrated the pancreatic islet and fewer β cells death by apoptosis within the inflamed islets were observed. More importantly, the CD4+ T cell proliferation was remarkably attenuated ex vivo in mice preventively treated with PHC (p < 0.01). In comparison to the PHC prevention group, no significant hypoglycemia, changes of insulin level and β cell protection were observed in mice treated with PHC after STZ administration. Our findings demonstrated that preventive administration of PHC protected β cells from apoptosis in type 1 diabetes induced by STZ, and the underlying mechanism may be involved in suppressing CD4+ T cells reaction, reducing inflammatory cells infiltration and protecting beta cell apoptosis in pancreatic islet.

Near-infrared fluorescence imaging with indocyanine green for quantification of changes in tissue perfusion following revascularization

Vascular ◽  
2021 ◽  
pp. 170853812110328
Author(s):  
Pim Van den Hoven ◽  
Floris S Weller ◽  
Merel Van De Bent ◽  
Lauren N Goncalves ◽  
Melissa Ruig ◽  
...  
Keyword(s):  
Indocyanine Green ◽  
Fluorescence Imaging ◽  
Fluorescence Intensity ◽  
Near Infrared ◽  
Tissue Perfusion ◽  
Control Group ◽  
Maximum Slope ◽  
Nir Fluorescence ◽  
Significant Difference ◽  
Revascularization Procedures

Objectives Current diagnostic modalities for patients with peripheral artery disease (PAD) mainly focus on the macrovascular level. For assessment of tissue perfusion, near-infrared (NIR) fluorescence imaging using indocyanine green (ICG) seems promising. In this prospective cohort study, ICG NIR fluorescence imaging was performed pre- and post-revascularization to assess changes in foot perfusion. Methods ICG NIR fluorescence imaging was performed in 36 patients with PAD pre- and post-intervention. After intravenous bolus injection of 0.1 mg/kg ICG, the camera registered the NIR fluorescence intensity over time on the dorsum of the feet for 15 min using the Quest Spectrum Platform®. Time-intensity curves were plotted for three regions of interest (ROI): (1) the dorsum of the foot, (2) the forefoot, and (3) the hallux. Time-intensity curves were normalized for maximum fluorescence intensity. Extracted parameters were the maximum slope, area under the curve (AUC) for the ingress, and the AUC for the egress. The non-treated contralateral leg was used as a control group. Results Successful revascularization was performed in 32 patients. There was a significant increase for the maximum slope and AUC egress in all three ROIs. The most significant difference was seen for the maximum slope in ROI 3 (3.7%/s to 6.6%/s, p < 0.001). In the control group, no significant differences were seen for the maximum slope and AUC egress in all ROIs. Conclusions This study shows the potential of ICG NIR fluorescence imaging in assessing the effect of revascularization procedures on foot perfusion. Future studies should focus on the use of this technique in predicting favorable outcome of revascularization procedures.

scholarly journals Moderate Intensity of Physical Exercise increased Β (Beta) Cell and Size of Langerhans Islets in Streptozotocin Induced Diabetes Mellitus Rats

2019 ◽  
Vol 1 (2) ◽  
pp. 52
Author(s):  
Sarah M Nurdin ◽  
Nuniek Nugraheni ◽  
Mei Wulan
Keyword(s):  
Diabetes Mellitus ◽  
Physical Exercise ◽  
Beta Cell ◽  
Moderate Intensity ◽  
Induction Treatment ◽  
Control Group ◽  
Β Cell ◽  
Moderate Intensity Exercise ◽  
Langerhans Islets ◽  
Significant Difference

Background: The death of β cells Langerhans islets in Diabetes Mellitus (DM) can cause  loss of Langerhans islet function and worsen the progression of DM. Physical exercise plays a major part in DM treatment.Aim: to observe the effect of moderate intensity exercise to β (beta) cell numbers and Langerhans islets area size in Streptozotocin (STZ) induced diabetes in rats.Methods: Thirty adult male Wistar rats (Rattusnorvegicus) divided into 3, Group 1 as the control, Group 2 received 35 mg/kg streptozotocin induction treatment, Group 3 received 35 mg/kg streptozotocin induction and physical exercise, swimming, with moderate intensity 70% from the swimming maximal ability, 9% of body weight load, 4 times a week for 4 weeks. Datas collected were in the form of histopathology slide of pancreatic tissue after receiving treatment for 28 days.Results: There are significant differences of β-cell pancreas number between group K1 and K2 (p<0,001), group K2 and to K3 (p<0,001). No significant difference between group K1 and K3 (p=0,102). The Langerhans islets area sizes of pancreas tissue between group K1, K2, and K3 are significantly different (p<0,001).Conclusion: This study shows moderate-intensity physical exercise can increase the number of β cell and average area size of Langerhans islets. The effect of physical exercise depends on the intensity of exercise and the capacity of pancreatic function left of the diabetic.

Moderate Intensity of Physical Exercise increased Β (Beta) Cell and Size of Langerhans Islets in Streptozotocin Induced Diabetes Mellitus Rats

2019 ◽  
Vol 1 (2) ◽  
pp. 52
Author(s):  
Sarah M Nurdin ◽  
Nuniek Nugraheni ◽  
Mei Wulan
Keyword(s):  
Diabetes Mellitus ◽  
Physical Exercise ◽  
Beta Cell ◽  
Moderate Intensity ◽  
Induction Treatment ◽  
Control Group ◽  
Β Cell ◽  
Moderate Intensity Exercise ◽  
Langerhans Islets ◽  
Significant Difference

Background: The death of β cells Langerhans islets in Diabetes Mellitus (DM) can cause  loss of Langerhans islet function and worsen the progression of DM. Physical exercise plays a major part in DM treatment.Aim: to observe the effect of moderate intensity exercise to β (beta) cell numbers and Langerhans islets area size in Streptozotocin (STZ) induced diabetes in rats.Methods: Thirty adult male Wistar rats (Rattusnorvegicus) divided into 3, Group 1 as the control, Group 2 received 35 mg/kg streptozotocin induction treatment, Group 3 received 35 mg/kg streptozotocin induction and physical exercise, swimming, with moderate intensity 70% from the swimming maximal ability, 9% of body weight load, 4 times a week for 4 weeks. Datas collected were in the form of histopathology slide of pancreatic tissue after receiving treatment for 28 days.Results: There are significant differences of β-cell pancreas number between group K1 and K2 (p<0,001), group K2 and to K3 (p<0,001). No significant difference between group K1 and K3 (p=0,102). The Langerhans islets area sizes of pancreas tissue between group K1, K2, and K3 are significantly different (p<0,001).Conclusion: This study shows moderate-intensity physical exercise can increase the number of β cell and average area size of Langerhans islets. The effect of physical exercise depends on the intensity of exercise and the capacity of pancreatic function left of the diabetic.

scholarly journals High sensitivity of β-cell replication to the inhibitory effects of interleukin-1β: modulation by adenoviral overexpression of IGF2 in rat islets

2009 ◽  
Vol 203 (1) ◽  
pp. 55-63 ◽  
Author(s):  
Elisabet Estil.les ◽  
Noèlia Téllez ◽  
Joan Soler ◽  
Eduard Montanya
Keyword(s):  
Cell Proliferation ◽  
Cell Apoptosis ◽  
Interleukin 1Β ◽  
Complete Suppression ◽  
Cell Replication ◽  
Inhibitory Effects ◽  
Β Cells ◽  
Β Cell ◽  
Rat Islets ◽  
Induced Apoptosis

Interleukin-1β (IL1B) is an important contributor to the autoimmune destruction of β-cells in type 1 diabetes, and it has been recently related to the development of type 2 diabetes. IGF2 stimulates β-cell proliferation and survival. We have determined the effect of IL1B on β-cell replication, and the potential modulation by IGF2 and glucose. Control-uninfected and adenovirus encoding for IGF2 (Ad-IGF2)-infected rat islets were cultured at 5.5 or 22.2 mmol/l glucose with or without 1, 10, 30, and 50 U/ml of IL1B. β-Cell replication was markedly reduced by 10 U/ml of IL1B and was almost nullified with 30 or 50 U/ml of IL1B. Higher concentrations of IL1B were required to increase β-cell apoptosis. Although IGF2 overexpression had a strong mitogenic effect on β-cells, IGF2 could preserve β-cell proliferation only in islets cultured with 10 U/ml IL1B, and had no effect with 30 and 50 U/ml of IL1B. In contrast, IGF2 overexpression induced a clear protection against IL1B-induced apoptosis, and higher concentrations of the cytokine were needed to increase β-cell apoptosis in Ad-IGF2-infected islets. These results indicate that β-cell replication is highly sensitive to the deleterious effects of the IL1B as shown by the inhibition of replication by relatively low IL1B concentrations, and the almost complete suppression of β-cell replication with high IL1B concentrations. Likewise, the inhibitory effects of IL-β on β-cell replication were not modified by glucose, and were only modestly prevented by IGF2 overexpression, in contrast with the higher protection against IL1B-induced apoptosis afforded by glucose and by IGF2 overexpression.

scholarly journals Dynamics of β-cell turnover: evidence for β-cell turnover and regeneration from sources of β-cells other than β-cell replication in the HIP rat

2009 ◽  
Vol 297 (2) ◽  
pp. E323-E330 ◽  
Author(s):  
Erica Manesso ◽  
Gianna M. Toffolo ◽  
Yoshifumi Saisho ◽  
Alexandra E. Butler ◽  
Aleksey V. Matveyenko ◽  
...  
Keyword(s):  
Cell Mass ◽  
Cell Formation ◽  
Cell Regeneration ◽  
Cell Turnover ◽  
Cell Replication ◽  
Wild Type ◽  
Β Cells ◽  
Β Cell ◽  
Islet Amyloid

Type 2 diabetes is characterized by hyperglycemia, a deficit in β-cells, increased β-cell apoptosis, and islet amyloid derived from islet amyloid polypeptide (IAPP). These characteristics are recapitulated in the human IAPP transgenic (HIP) rat. We developed a mathematical model to quantify β-cell turnover and applied it to nondiabetic wild type (WT) vs. HIP rats from age 2 days to 10 mo to establish 1) whether β-cell formation is derived exclusively from β-cell replication, or whether other sources of β-cells (OSB) are present, and 2) to what extent, if any, there is attempted β-cell regeneration in the HIP rat and if this is through β-cell replication or OSB. We conclude that formation and maintenance of adult β-cells depends largely (∼80%) on formation of β-cells independent from β-cell duplication. Moreover, this source adaptively increases in the HIP rat, implying attempted β-cell regeneration that substantially slows loss of β-cell mass.

scholarly journals Effect of Sago Analog Rice and Red Bean Diet to β Cells Pancreas Refinement in STZ-NA Induced Diabetic Rats

2020 ◽  
pp. 667-673
Author(s):  
Sri Budi Wahjuningsih ◽  
Haslina Haslina ◽  
Agus Tri Putranto ◽  
Mita Nurul Azkia
Keyword(s):  
Blood Glucose ◽  
Blood Glucose Level ◽  
Glucose Level ◽  
Insulin Level ◽  
Diabetic Rats ◽  
Diabetic Group ◽  
Pancreatic Β Cell ◽  
Β Cells ◽  
Β Cell ◽  
Red Bean

The study aims to determine the effect of sago analogue rice and red beans in diabetic rats to repair pancreatic β-cells. Thirty-five males Wistar rats were divided into 5 groups: normal group diet (STD), the diabetic group (STDD) with a standard feed diet, the diabetic group with mentik wangi rice (MWRD), the diabetic group with sago analogue rice (SARD) and the diabetic group with sago analogue rice with the addition of 10% red bean flour (SARKBD). All groups were analysed for dietary interventions, blood glucose level, insulin level for HOMA-β and HOMA S indices and measurement of insulin level by using IHC analysis. In addition, short-chain fatty acids (SCFA) analysis was performed in the caecum. This study showed that decreasing blood glucose level shown in SARD and RASKBD groups. The pancreatic β-cell number indicated an increase in the SARD group compares to the STDD group. The pool total of SCFA in SARD group was the highest among of all groups, as well as the acetate, propionate and butyrate pools. These results indicate that the sago analogue rice diet could repair and increase the expression of pancreatic β-cell through absorption inhibition mechanisms and by increasing insulin sensitivity and the SCFA level.

scholarly journals UCN2: a new candidate influencing pancreatic β-cell adaptations in pregnancy

2020 ◽  
Vol 245 (2) ◽  
pp. 247-257
Author(s):  
Sian J S Simpson ◽  
Lorna I F Smith ◽  
Peter M Jones ◽  
James E Bowe
Keyword(s):  
Glucose Tolerance ◽  
Pancreatic Islet ◽  
Adaptive Responses ◽  
Β Cells ◽  
Β Cell ◽  
Pregnant Mice ◽  
Pregnant State ◽  
Islet Physiology ◽  
Circulating Levels ◽  
Stimulate Insulin Release

The corticotropin-releasing hormone (CRH) family of peptides, including urocortin (UCN) 1, 2 and 3, are established hypothalamic neuroendocrine peptides, regulating the physiological and behaviour responses to stress indirectly, via the hypothalamic-pituitary-adrenal (HPA) axis. More recently, these peptides have been implicated in diverse roles in peripheral organs through direct signalling, including in placental and pancreatic islet physiology. CRH has been shown to stimulate insulin release through activation of its cognate receptors, CRH receptor 1 (CRHR1) and 2. However, the physiological significance of this is unknown. We have previously reported that during mouse pregnancy, expression of CRH peptides increase in mouse placenta suggesting that these peptides may play a role in various biological functions associated with pregnancy, particularly the pancreatic islet adaptations that occur in the pregnant state to compensate for the physiological increase in maternal insulin resistance. In the current study, we show that mouse pregnancy is associated with increased circulating levels of UCN2 and that when we pharmacologically block endogenous CRHR signalling in pregnant mice, impairment of glucose tolerance is observed. This effect on glucose tolerance was comparable to that displayed with specific CRHR2 blockade and not with specific CRHR1 blockade. No effects on insulin sensitivity or the proliferative capacity of β-cells were detected. Thus, CRHR2 signalling appears to be involved in β-cell adaptive responses to pregnancy in the mouse, with endogenous placental UCN2 being the likely signal mediating this.

scholarly journals The Effect of Cigarette Smoke Exposure in the Fetal Growth and Fetal Development of Mice (Mus musculus)

2020 ◽  
Vol 11 (1) ◽  
pp. 13
Author(s):  
Endy Novryan Ridwan ◽  
Martono Tri Utomo ◽  
Harianto Notopuro
Keyword(s):  
Cigarette Smoke ◽  
Fetal Growth ◽  
Mus Musculus ◽  
Fetal Development ◽  
Ambient Air ◽  
Smoke Exposure ◽  
Cigarette Smoke Exposure ◽  
Control Group ◽  
Significant Difference ◽  
Pregnant Mice

Introduction: This research aims to investigate and observe the effect of cigarette smoke exposure in the fetal growth and fetal development of mice (Mus musculus).  Methods: This was an experiment with post-test only control group design. The sample of the research was 36 pregnant mice which were randomly divided into 2 groups: control group (K) pregnant mice which inhaled ambient air without cigarette smoke exposure, and treatment group (P) pregnant mice which were given cigarette smoke exposure for 14 days with 2 bars of cigarette each day.  Results: The results showed a significant difference in the fetal birth weight between the group exposed to cigarette smoke (p < 0.05) compared with the control group. Fetal defect and stillbirth were not found in this research. Conclusion: The exposure of cigarette smoke gave negative effects of fetal growth and development because of the free radicals generated.

scholarly journals IL-17A is involved in diabetic inflammatory pathogenesis by its receptor IL-17RA

2020 ◽  
pp. 153537022095694
Author(s):  
Ao-Wang Qiu ◽  
Xin Cao ◽  
Wei-Wei Zhang ◽  
Qing-Huai Liu
Keyword(s):  
Cell Apoptosis ◽  
Spontaneous Mutation ◽  
Insulin Level ◽  
Β Cells ◽  
Β Cell ◽  
Pancreatic Β Cells ◽  
Min6 Cells ◽  
Tnf Α ◽  
Direct Injury ◽  
Akita Mice

Interleukin (IL)-17A, a proinflammatory cytokine produced by T-helper (Th)17 cells, has been associated with autoimmune diseases. Type 1 diabetes (T1D) is caused either due to mutation of insulin gene or developed as an autoimmune disease. Studies have shown that IL-17A expression is upregulated in the pancreas in T1D patients and animal models. However, role or importance of IL-17A in T1D pathogenesis needs elucidation. Particularly, evidence for a direct injury of IL-17A to pancreatic β cells through activating IL-17 receptor A (IL-17RA) is lacking. Ins2Akita (Akita) mouse, a T1D model with spontaneous mutation in insulin 2 gene leading to β-cell apoptosis, was crossed with IL-17A-knockout mouse and male IL-17A-deficient Akita mice were used. Streptozotocin, a pancreatic β-cell-specific cytotoxin, was employed to induce a diabetic model in MIN6 cells, a mouse insulinoma cell line. IL-17A expression in the pancreas was upregulated in both Akita and streptozotocin-induced diabetic mice. IL-17A-knockout Akita mice manifested reduced blood glucose concentration and raised serum insulin level. IL-17A deficiency also decreased production of the proinflammatory cytokines tumor necrosis factor (TNF)-α, IL-1β, and interferon (IFN)-γ in Akita mice. IL-17RA expression in MIN6 cells was upregulated by IL-17A. IL-17A enhanced expression of TNF-α, IL-1β, IFN-γ, and inducible nitric oxide synthase (iNOS) and further increased streptozotocin-induced expression of the inflammatory factors in MIN6 cells. IL-17A exacerbated streptozotocin-induced MIN6 cell apoptosis and insulin secretion impairment. Blocking IL-17RA with anti-IL-17RA-neutralizing antibody reduced all these deleterious effects of IL-17A on MIN6 cells. Collectively, IL-17A deficiency alleviated hyperglycemia, hypoinsulinemia, and inflammatory response in Akita mice that are characteristic for T1D. IL-17A exerted an alone and synergistic destruction with streptozotocin to pancreatic β cells through IL-17RA pathway. Thus, the data suggest that targeting IL-17A and/or IL-17RA is likely to preserve remaining β-cell function and treat T1D. Impact statement The participation of interleukin (IL)-17A in diabetic pathogenesis is suggested in animal models of autoimmune diabetes and in patients with type 1 diabetes (T1D), but with some contradictory results. Particularly, evidence for a direct injury of IL-17A to pancreatic β cells is lacking. We showed that IL-17A deficiency alleviated diabetic signs including hyperglycemia, hypoinsulinemia, and inflammatory response in Ins2Akita (Akita) mice, a T1D model with spontaneous mutation in insulin 2 gene leading to β-cell apoptosis. IL-17A enhanced inflammatory reaction, oxidative stress, and cell apoptosis but attenuated insulin level in mouse insulin-producing MIN6 cells. IL-17A had also a synergistic destruction to MIN6 cells with streptozotocin (STZ), a pancreatic β-cell-specific cytotoxin. Blocking IL-17 receptor A (IL-17RA) reduced all these deleterious effects of IL-17A on MIN6 cells. The results demonstrate the role and the importance of IL-17A in T1D pathogenesis and suggest a potential therapeutic strategy for T1D targeting IL-17A and/or IL-17RA.

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