scholarly journals Acetone Ingestion Mimics a Fasting State to Improve Glucose Tolerance in a Mouse Model of Gestational Hyperglycemia

2021 ◽  
Vol 22 (23) ◽  
pp. 12914
Author(s):  
Sandra Szlapinski ◽  
Brenda Strutt ◽  
Madeline Deane ◽  
Edith Arany ◽  
Jamie Bennett ◽  
...  
Keyword(s):  
Glucose Tolerance ◽  
Mouse Model ◽  
Islet Cells ◽  
Post Partum ◽  
Cell Mass ◽  
Tolerance Test ◽  
Transient Effects ◽  
Β Cell ◽  
Cell Conversion ◽  
Pregnant Mice

Gestational diabetes mellitus results, in part, from a sub-optimal β-cell mass (BCM) during pregnancy. Artemisinins were reported to increase BCM in models of diabetes by α- to β-cell conversion leading to enhanced glucose tolerance. We used a mouse model of gestational glucose intolerance to compare the effects of an artemisinin (artesunate) on glycemia of pregnant mice with vehicle treatment (acetone) or no treatment. Animals were treated daily from gestational days (GD) 0.5 to 6.5. An intraperitoneal glucose tolerance test was performed prior to euthanasia at GD18.5 or post-partum. Glucose tolerance was significantly improved in both pregnant and non-pregnant mice with both artesunate and vehicle-alone treatment, suggesting the outcome was primarily due to the acetone vehicle. In non-pregnant, acetone-treated animals, improved glucose tolerance was associated with a higher BCM and a significant increase in bihormonal insulin and glucagon-containing pancreatic islet cells, suggesting α- to β-cell conversion. BCM did not differ with treatment during pregnancy or post-partum. However, placental weight was higher in acetone-treated animals and was associated with an upregulation of apelinergic genes. Acetone-treated animals had reduced weight gain during treatment despite comparable food consumption to non-treated mice, suggesting transient effects on nutrient uptake. The mean duodenal and ileum villus height was reduced following exposure to acetone. We conclude that acetone treatment may mimic transient fasting, resulting in a subsequent improvement in glucose tolerance during pregnancy.

scholarly journals Pancreatic Islet APJ Deletion Reduces Islet Density and Glucose Tolerance in Mice

Endocrinology ◽  
2015 ◽  
Vol 156 (7) ◽  
pp. 2451-2460 ◽  
Author(s):  
Song Han ◽  
Ella W. Englander ◽  
Guillermo A. Gomez ◽  
Cristiana Rastellini ◽  
Thomas Quertermous ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Glucose Tolerance ◽  
Pancreatic Islet ◽  
Glucose Tolerance Test ◽  
Islet Cells ◽  
Tolerance Test ◽  
Β Cell ◽  
Glucose Clearance ◽  
Islet Size ◽  
Glucose Stimulated Insulin Secretion

Protection and replenishment of a functional pancreatic β-cell mass (BCM) are key goals of all diabetes therapies. Apelin, a small regulatory peptide, is the endogenous ligand for the apelin receptor (APJ) receptor. The apelin-APJ signaling system is expressed in rodent and human islet cells. Apelin exposure has been shown to inhibit and to stimulate insulin secretion. Our aim was to assess the influence of a selective APJ deletion in pancreatic islet cells on islet homeostasis and glucose tolerance in mice. Cre-LoxP strategy was utilized to mediate islet APJ deletion. APJ deletion in islet cells (APJΔislet) resulted in a significantly reduced islet size, density and BCM. An ip glucose tolerance test showed significantly impaired glucose clearance in APJΔislet mice. APJΔislet mice were not insulin resistant and in vivo glucose-stimulated insulin secretion was reduced modestly. In vitro glucose-stimulated insulin secretion showed a significantly reduced insulin secretion by islets from APJΔislet mice. Glucose clearance in response to ip glucose tolerance test in obese APJΔislet mice fed a chronic high-fat (HF) diet, but not pregnant APJΔislet mice, was impaired significantly. In addition, the obesity-induced adaptive elevations in mean islet size and fractional islet area were reduced significantly in obese APJΔislet mice when compared with wild-type mice. Together, these findings demonstrate a stimulatory role for the islet cell apelin-APJ signaling axis in regulation of pancreatic islet homeostasis and in metabolic induced β-cell hyperplasia. The results indicate the apelin-APJ system can be exploited for replenishment of BCM.

scholarly journals Protective Role of Recombinant Human Thrombomodulin in Diabetes Mellitus

Cells ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 2237
Author(s):  
Yuko Okano ◽  
Atsuro Takeshita ◽  
Taro Yasuma ◽  
Masaaki Toda ◽  
Kota Nishihama ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Glucose Tolerance ◽  
Mouse Model ◽  
Pancreatic Islet ◽  
Glucose Intolerance ◽  
Cell Mass ◽  
Diabetic Mice ◽  
Β Cells ◽  
Β Cell ◽  
Diabetes Mouse

Diabetes mellitus is a global threat to human health. The ultimate cause of diabetes mellitus is insufficient insulin production and secretion associated with reduced pancreatic β-cell mass. Apoptosis is an important and well-recognized mechanism of the progressive loss of functional β-cells. However, there are currently no available antiapoptotic drugs for diabetes mellitus. This study evaluated whether recombinant human thrombomodulin can inhibit β-cell apoptosis and improve glucose intolerance in a diabetes mouse model. A streptozotocin-induced diabetes mouse model was prepared and treated with thrombomodulin or saline three times per week for eight weeks. The glucose tolerance and apoptosis of β-cells were evaluated. Diabetic mice treated with recombinant human thrombomodulin showed significantly improved glucose tolerance, increased insulin secretion, decreased pancreatic islet areas of apoptotic β-cells, and enhanced proportion of regulatory T cells and tolerogenic dendritic cells in the spleen compared to counterpart diseased mice treated with saline. Non-diabetic mice showed no changes. This study shows that recombinant human thrombomodulin, a drug currently used to treat patients with coagulopathy in Japan, ameliorates glucose intolerance by protecting pancreatic islet β-cells from apoptosis and modulating the immune response in diabetic mice. This observation points to recombinant human thrombomodulin as a promising antiapoptotic drug for diabetes mellitus.

scholarly journals Dietary sodium chloride attenuates increased β-cell mass to cause glucose intolerance in mice under a high-fat diet

PLoS ONE ◽  
2021 ◽  
Vol 16 (3) ◽  
pp. e0248065
Author(s):  
Keigo Taki ◽  
Hiroshi Takagi ◽  
Tomonori Hirose ◽  
Runan Sun ◽  
Hiroshi Yaginuma ◽  
...  
Keyword(s):  
Glucose Tolerance ◽  
Glucose Intolerance ◽  
Plasma Glucose ◽  
High Fat Diet ◽  
Cell Mass ◽  
Tolerance Test ◽  
Chow Diet ◽  
High Fat ◽  
Lower Plasma ◽  
Β Cell

Excessive sodium salt (NaCl) or fat intake is associated with a variety of increased health risks. However, whether excessive NaCl intake accompanied by a high-fat diet (HFD) affects glucose metabolism has not been elucidated. In this study, C57BL/6J male mice were fed a normal chow diet (NCD), a NCD plus high-NaCl diet (NCD plus NaCl), a HFD, or a HFD plus high-NaCl diet (HFD plus NaCl) for 30 weeks. No significant differences in body weight gain, insulin sensitivity, and glucose tolerance were observed between NCD-fed and NCD plus NaCl-fed mice. In contrast, body and liver weights were decreased, but the weight of epididymal white adipose tissue was increased in HFD plus NaCl-fed compared to HFD-fed mice. HFD plus NaCl-fed mice had lower plasma glucose levels in an insulin tolerance test, and showed higher plasma glucose and lower plasma insulin levels in an intraperitoneal glucose tolerance test compared to HFD-fed mice. The β-cell area and number of islets were decreased in HFD plus NaCl-fed compared to HFD-fed mice. Increased Ki67-positive β-cells, and increased expression levels of Ki67, CyclinB1, and CyclinD1 mRNA in islets were observed in HFD-fed but not HFD plus NaCl-fed mice when compared to NCD-fed mice. Our data suggest that excessive NaCl intake accompanied by a HFD exacerbates glucose intolerance, with impairment in insulin secretion caused by the attenuation of expansion of β-cell mass in the pancreas.

Swim training prevents hyperglycemia in ZDF rats: mechanisms involved in the partial maintenance of β-cell function

2008 ◽  
Vol 294 (2) ◽  
pp. E271-E283 ◽  
Author(s):  
Michael A. Király ◽  
Holly E. Bates ◽  
Natalia A. Kaniuk ◽  
Jessica T. Y. Yue ◽  
John H. Brumell ◽  
...  
Keyword(s):  
Glucose Tolerance ◽  
Cell Function ◽  
Cell Mass ◽  
Area Under The Curve ◽  
Tolerance Test ◽  
Β Cell ◽  
Β Cell Function ◽  
Old Rats ◽  
Zdf Rats ◽  
Mass Expansion

Exercise improves glucose tolerance in obese rodent models and humans; however, effects with respect to mechanisms of β-cell compensation remain unexplained. We examined exercise's effects during the progression of hyperglycemia in male Zucker diabetic fatty (ZDF) rats until 19 wk of age. At 6 wk old, rats were assigned to 1) basal-euthanized for baseline values; 2) exercise-swam individually for 1 h/day, 5 days/wk; and 3) controls ( n = 8–10/group). Exercise (13 wk) resulted in maintenance of fasted hyperinsulinemia and prevented increases in fed and fasted glucose ( P < 0.05) compared with sham-exercised and sedentary controls ( P < 0.05). β-Cell function calculations indicate prolonged β-cell adaptation in exercised animals alone. During an intraperitoneal glucose tolerance test (IPGTT), exercised rats had lower 2-h glucose ( P < 0.05) vs. controls. Area-under-the-curve analyses from baseline for IPGTT glucose and insulin indicate improved glucose tolerance with exercise was associated with increased insulin production and/or secretion. β-Cell mass increased in exercised vs. basal animals; however, mass expansion was absent at 19 wk in controls ( P < 0.05). Hypertrophy and replication contributed to expansion of β-cell mass; exercised animals had increased β-cell size and bromodeoxyuridine incorporation rates vs. controls ( P < 0.05). The relative area of GLUT2 and protein kinase B was significantly elevated in exercised vs. sedentary controls ( P < 0.05). Last, we show formation of ubiquitinated protein aggregates, a response to cellular/oxidative stress, occurred in nonexercised 19 wk-old ZDF rats but not in lean, 6 wk-old basal, or exercised rats. In conclusion, improved β-cell compensation through increased β-cell function and mass occurs in exercised but not sedentary ZDF rats and may be in part responsible for improved glucoregulation.

scholarly journals Development of a Nongenetic Mouse Model of Type 2 Diabetes

2011 ◽  
Vol 2011 ◽  
pp. 1-12 ◽  
Author(s):  
Elizabeth R. Gilbert ◽  
Zhuo Fu ◽  
Dongmin Liu
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Mouse Model ◽  
Serum Insulin ◽  
Cell Mass ◽  
Low Fat ◽  
Β Cell ◽  
Islet Mass ◽  
Metabolic Characteristics

Insulin resistance and loss of β-cell mass cause Type 2 diabetes (T2D). The objective of this study was to generate a nongenetic mouse model of T2D. Ninety-six 6-month-old C57BL/6N males were assigned to 1 of 12 groups including (1) low-fat diet (LFD; low-fat control; LFC), (2) LFD with 1 i.p. 40 mg/kg BW streptozotocin (STZ) injection, (3), (4), (5), (6) LFD with 2, 3, 4, or 5 STZ injections on consecutive days, respectively, (7) high-fat diet (HFD), (8) HFD with 1 STZ injection, (9), (10), (11), (12) HFD with 2, 3, 4, or 5 STZ injections on consecutive days, respectively. After 4 weeks, serum insulin levels were reduced in HFD mice administered at least 2 STZ injections as compared with HFC. Glucose tolerance was impaired in mice that consumed HFD and received 2, 3, or 4 injections of STZ. Insulin sensitivity in HFD mice was lower than that of LFD mice, regardless of STZ treatment. Islet mass was not affected by diet but was reduced by 50% in mice that received 3 STZ injections. The combination of HFD and three 40 mg/kg STZ injections induced a model with metabolic characteristics of T2D, including peripheral insulin resistance and reduced β-cell mass.

scholarly journals Metabolic and Genetic Determinants of Glucose Shape After Oral Challenge in Obese Youths: A Longitudinal Study

2020 ◽  
Vol 105 (2) ◽  
pp. 534-542 ◽  
Author(s):  
Alfonso Galderisi ◽  
Domenico Tricò ◽  
Chiara Dalla Man ◽  
Nicola Santoro ◽  
Bridget Pierpont ◽  
...  
Keyword(s):  
Glucose Tolerance ◽  
Risk Allele ◽  
Tolerance Test ◽  
Metabolic Phenotype ◽  
Oral Glucose ◽  
Late Time ◽  
Β Cell ◽  
Group A ◽  
Oral Minimal Model ◽  
Tcf7l2 Rs7903146

Abstract Context The time-to-glucose-peak following the oral glucose tolerance test (OGTT) is a highly reproducible marker for diabetes risk. In obese youths, we lack evidence for the mechanisms underlying the effects of the TCF7L2 rs7903146 variant on glucose peak. Methods We analyzed the metabolic phenotype and the genotype for the TCF7L2 rs7903146 in 630 obese youths with normal (NGT) and impaired (IGT) glucose tolerance. Participants underwent a 3-hour, 9-point OGTT to estimate, using the oral minimal model, the disposition index (DI), the static (φstatic) and dynamic (φdynamic) components β-cell responsiveness and insulin sensitivity (SI). In a subgroup (n = 241) longitudinally followed for 2 years, we estimated the effect of time-to-glucose-peak on glucose tolerance change. Results Participants were grouped into early (&lt;30 minutes) and late (≥30 minutes) glucose peakers. A delayed glucose peak was featured by a decline in φstatic (P &lt; .001) in the absence of a difference in φdynamic. The prevalence of T-risk allele for TCF7L2 rs7903146 variant significantly increased in the late peak group. A lower DI was correlated with higher glucose concentration at 1 and 2 hours, whereas SI was inversely associated with 1-hour glucose. Glucose peak &lt;30 minutes was protective toward worsening of glucose tolerance overtime (odds ratio 0.35 [0.15–0.82]; P = .015), with no subjects progressing to NGT or persisting IGT, in contrast to the 40% of progressor in those with late glucose peak. Conclusion The prevalence of T-risk allele for the TCF7L2 rs7903146 prevailed in the late time-to-glucose peak group, which in turn is associated with impaired β-cell responsiveness to glucose (φ), thereby predisposing to prediabetes and diabetes in obese youths.

scholarly journals Alpha to Beta Cell Conversion in the Postpartum Mouse Pancreas involves Lgr5 Progeny

2021 ◽  
Author(s):  
Uylissa A. Rodriguez ◽  
Mairobys Socorro ◽  
Angela Criscimanna ◽  
Christina P. Martins ◽  
Nada Mohamed ◽  
...  
Keyword(s):  
Intermediate Phase ◽  
Cell Mass ◽  
Cell Lineage ◽  
Stem Cell Marker ◽  
Tamoxifen Treatment ◽  
Diabetic Patients ◽  
Mass Reduction ◽  
Β Cell ◽  
Cell Compartment ◽  
Cell Conversion

In contrast to the skin and the gut, where somatic stem cells and their niche are well characterized, a definitive pancreatic multipotent cell population in the adult pancreas has yet to be revealed. Of particular interest is whether such cells may be endogenous in diabetic patients, and if so, can they be used for therapeutic purposes. In the current study, we used two separate reporter lines to target Cre-recombinase expression to the Lgr5 or glucagon expressing cells in the pancreas. We provide evidence for the existence of a population of cells within and in the proximity of the ducts that transiently express the stem cell marker Lgr5 during late gestational stages. Careful timing of tamoxifen treatment in <i>Lgr5<sup>EGFP-IRES-CreERT2</sup></i>;R26<i><sup>Tomato</sup></i> mice allowed us to show that these <i>Lgr5</i>-expressing progenitor cells can differentiate into α-cells during pregnancy. Furthermore, we report on a spontaneous α-to β-cell lineage conversion specifically after parturition. The contribution of Lgr5-progeny to the β-cell compartment through an α-cell intermediate phase early on after pregnancy appears to be part of a novel mechanism that would counterbalance against excessive β-cell mass reduction during β-cell involution.

scholarly journals Schätzung des Prüfniveaus metabolischer Merkmale beim Glukose-Toleranz-Test (GTT) an Jungbullen

2003 ◽  
Vol 46 (2) ◽  
pp. 167-176 ◽  
Author(s):  
L. Panicke ◽  
E. Fischer ◽  
B. Fischer ◽  
R. Staufenbiel
Keyword(s):  
Glucose Tolerance ◽  
Glucose Tolerance Test ◽  
Post Partum ◽  
Tolerance Test ◽  
The Other ◽  
Metabolic Parameters ◽  
Breeding Value ◽  
One Year ◽  
Pedigree Breeding ◽  
Selection Of

Abstract. Title of the paper: Level estimation of metabolic parameters in the glucose tolerance test (GTT) of young bulls The metabolic parameters of the glucose tolerance test are suitable for an additional recommendation for the valuation of the breeding bulls before the start of the offspring’s test could be given. Very important is the level of glucose half live to the begin of lactation of the cows. The other limit is the hyperglycemias greater than 10 mmol/l (or 180 mg/dl) in the glucose level in the blood. The glucose half live measured nearly 48 minutes is comparable in the 8th week post partum in lactation of cows with the young bulls in the age one year. Their combination with the pedigree breeding value is leading to increase of information, that could be utilised to the selection of improper bulls if the present results were confirmed.

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