Ghrelin mitigates <i>β</i>‐cell mass loss during insulitis in an animal model of autoimmune diabetes mellitus, the BioBreeding/Worcester rat

Baena-Nieto, Gloria; Lomas-Romero, Isabel M.; Mateos, Rosa M.; Leal-Cosme, Noelia; Pérez-Arana, Gonzalo M; Diosdado, Manuel Aguilar; Segundo, Carmen

doi:10.1002/dmrr.2813

Cited by 10 publications

(13 citation statements)

References 51 publications

(70 reference statements)

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“…Many of these studies focused on several hormones that were responsible for beta-cell changes. The effect of glucagon-like peptide 1 (GLP-1) or ghrelin on insulin production and the protective role of GLP-1 on beta-cell mass is well-known [1,2]. In contrast, changes in the alpha-cell population and glucagon release have not been studied enough.…”

Section: Introductionmentioning

confidence: 99%

Glucagon-Producing Cell Expansion in Wistar Rats. Changes to Islet Architecture After Sleeve Gastrectomy

et al. 2021

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Purpose Many studies about bariatric surgery have analyzed the effect of sleeve gastrectomy (SG) on glucose improvement, beta-cell mass, and islet size modification. The effects of SG on the other endocrine cells of the pancreas, such as the alpha-cell population, and their regulatory mechanisms remain less studied. Materials and Methods We focused our work on the changes in the alpha-cell population after SG in a healthy model of Wistar rats. We measured alpha-cell mass, glucose tolerance, and insulin release after oral glucose tolerance tests and plasma glucagon secretion patterns after insulin infusion. Three Wistar rat groups were employed: SG-operated, surgical control (Sham), and fasting control. Results The results obtained showed significant increases in the alpha-cell population after SG. The result was an increase in beta-cell transdifferentiation; it was shown by some expressed molecules (the loss of expression of Pdx-1 and the increase in Arx and Pax6 cells/mm2 of islet). The serum results were enhanced plasma glucagon secretion pattern after insulin infusion assays and normal glucose tolerance and insulin release after OGTT. Conclusion We concluded that SG leads to an expansion of the alpha-cell population, at expense of beta-cell; this expansion of alpha-cells is related to transdifferentiation. Plasma glucose level was not affected due to an increased glucagon response.

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Section: Introductionmentioning

confidence: 99%

Glucagon-Producing Cell Expansion in Wistar Rats. Changes to Islet Architecture After Sleeve Gastrectomy

et al. 2021

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“…Increased serum ghrelin level, lower blood glucose levels and food intake were observed in mice in the T1DM + HBO group. A potential explanation is that the enhanced ghrelin activity could've exerted anti-inflammatory effects on the pancreas ( 32 ), but not to a level sufficient to trigger feeding behavior. McFarlane et al ( 55 ) previously demonstrated that stimulating food intake in mice via exogenous injection of ghrelin notably increased plasma ghrelin levels.…”

Section: Discussionmentioning

confidence: 99%

“…In particular, it has also been demonstrated that overexpression of intra-islet ghrelin increases the proliferation of islet β-cells in a streptozotocin (STZ)-induced β-cell injury model ( 31 ). Exogenous injection of ghrelin has been demonstrated to delay the development of autoimmune diabetes by mitigating insulitis and β-cell mass loss in BioBreeding/Worcester rats ( 32 ). Furthermore, certain studies have found that ghrelin regulates GLUT2 expression ( 33 , 34 ) and stimulate hepatic gluconeogenesis ( 35 ).…”

Section: Introductionmentioning

confidence: 99%

Ghrelin system is involved in improvements in glucose metabolism mediated by hyperbaric oxygen treatment in a streptozotocin‑induced type�1 diabetes mouse model

et al. 2020

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Type 1 diabetes mellitus (T1dM) is an autoimmune disorder for which the only effective therapy is insulin replacement. Hyperbaric oxygen (HBo) therapy has demonstrated potential in improving hyperglycemia and as a treatment option for T1dM. Ghrelin and HBo have been previously reported to exert proliferative, anti-apoptotic and anti-inflammatory effects in pancreatic cells. The present study investigated the mechanism underlying HBo-and ghrelin system-mediated regulation of glucose metabolism. Male c57Bl/6 mice were intraperitoneally injected with streptozotocin (STZ; 150 mg/kg) to induce T1dM before the diabetic mice were randomly assigned into the T1dM and T1dM + HBo groups. Mice in the T1dM + HBo group received HBo (1 h; 100% oxygen; 2 atmospheres absolute) daily for 2 weeks. Significantly lower blood glucose levels and food intake were observed in mice in the T1dM + HBo group. Following HBo treatment, islet β-cell area were increased whereas those of α-cell were decreased in the pancreas. in addition, greater hepatic glycogen storage in liver was observed, which coincided with higher pancreatic glucose transporter 2 (GluT2) expression levels and reduced hepatic GluT2 membrane trafficking. There were also substantially higher total plasma ghrelin concentrations and gastric ghrelin-o-acyl transferase (GoaT) expression levels in mice in the T1dM + HBo group. HBo treatment also abolished reductions in pancreatic GoaT expression levels in T1dM mice. additionally, hepatic growth hormone secretagogue receptor-1a levels were found to be lower in mice in the T1dM + HBo group compared with those in the T1dM group. These results suggest that HBo administration improved glucose metabolism in a STZ-induced T1dM mouse model. The underlying mechanism involves improved insulin-release, glucose-sensing and regulation of hepatic glycogen storage, an observation that was also likely dependent on the ghrelin signalling system.

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“…Consequently, two slides were selected from each animal, and five fields (200x or 400x) in each slide were randomly selected for calculating the MOD. β-cell mass (66) was obtained by the following formula: β-cell mass= (total β-cell area/total pancreatic area) × pancreas weight (mg). Perifusion secretion assay of native mouse islets.…”

Section: Histopathologymentioning

confidence: 99%

Tectorigenin enhances PDX1 expression and protects pancreatic β-cells by activating ERK and reducing ER stress

Yao

Chen

et al. 2020

Journal of Biological Chemistry

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Pancreas/duodenum homeobox protein 1 (PDX1) is an important transcription factor that regulates islet β-cell proliferation, differentiation, and function. Reduced expression of PDX1 is thought to contribute to β-cell loss and dysfunction in diabetes. Thus, promoting PDX1 expression can be an effective strategy to preserve β-cell mass and function. Previously, we established a PDX1 promoter-dependent luciferase system to screen agents that can promote PDX1 expression. Natural compound tectorigenin (TG) was identified as a promising candidate that could enhance the activity of the promoter for PDX1 gene. In this study, we first demonstrated that TG could promote the expression of PDX1 in β-cells via activating extracellular signal-related kinase (ERK), as indicated by increased phosphorylation of ERK; this effect was observed under either normal or glucotoxic/lipotoxic conditions. We then found that TG could suppress induced apoptosis and improved the viability of β-cells under glucotoxicity and lipotoxicity by activation of ERK and reduction of reactive oxygen species (ROS) and endoplasmic reticulum (ER) stress. These effects held true in vivo as well: prophylactic or therapeutic use of TG could obviously inhibit ER stress and decrease islet β-cell apoptosis in the pancreas of mice given a high-fat/high-sucrose diet (HFHSD), thus dramatically maintaining or restoring β-cell mass and islet size respectively. Accordingly, both prophylactic and therapeutic use of TG improved HFHSD impaired glucose metabolism in mice, as evidenced by ameliorating hyperglycemia and glucose intolerance. Taken together, TG, as an agent promoting PDX1 expression exhibits strong protective effects on islet β-cells both in vitro and in vivo.

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Ghrelin mitigates β‐cell mass loss during insulitis in an animal model of autoimmune diabetes mellitus, the BioBreeding/Worcester rat

Cited by 10 publications

References 51 publications

Glucagon-Producing Cell Expansion in Wistar Rats. Changes to Islet Architecture After Sleeve Gastrectomy

Glucagon-Producing Cell Expansion in Wistar Rats. Changes to Islet Architecture After Sleeve Gastrectomy

Ghrelin system is involved in improvements in glucose metabolism mediated by hyperbaric oxygen treatment in a streptozotocin‑induced type�1 diabetes mouse model

Tectorigenin enhances PDX1 expression and protects pancreatic β-cells by activating ERK and reducing ER stress

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