Mechanisms involved in the beta-cell mass increase induced by chronic sucrose feeding to normal rats

Zotto, H Del; Dumm, CL Gomez; Drago, Silvina Rosa; Fortino, Alejandra; Luna, GC; Gagliardino, J J

doi:10.1677/joe.0.1740225

Cited by 19 publications

(14 citation statements)

References 32 publications

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“…Nevertheless, postprandial glucose and insulin levels, which were not measured, might have differed as reported previously by our group (10,11). Other investigators have also reported that sucrose and other high glycemic starch amylopectin can induce islet hypertrophy (31)(32)(33). Furthermore, amylopectin-fed rats had larger and more fibrotic islets than low glycemic-amylose-fed rats without decrease in insulin sensitivity (32).…”

Section: Discussionmentioning

confidence: 56%

Palatinose and oleic acid act together to prevent pancreatic islet disruption in nondiabetic obese Zucker rats

et al. 2008

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: We showed previously that 8-wk consumption of a diet containing palatinose (P, a slowly-absorbed sucrose analogue) and oleic acid (O) ameliorates but a diet containing sucrose (S) and linoleic acid (L) aggravates metabolic abnormalities in Zucker fatty (fa/fa) rats. In this study, we aimed to identify early changes in metabolism in rats induced by certain combinations of carbohydrates and fatty acids. Specifically, male Zucker fatty rats were fed an isocaloric diet containing various combinations of carbohydrates (P ; S) and fatty acids (O ; L). After 4 wk, no significant differences in body weight, visceral fat mass, plasma parameters (glucose, insulin, lipids, and adipokines), hepatic adiposity and gene expression, and adipose inflammation were observed between dietary groups. In contrast, pancreatic islets of palatinose-fed (PO and PL) rats were smaller and less fibrotic than sucrose-fed (SO and SL) rats. The abnormal ! -cell distribution and sporadic staining of active caspase-3 common to islets of linoleic-acid-fed rats were not observed in oleic-acid-fed (PO and SO) rats. Accordingly, progressive " -cell loss was seen in SL rats, but not in PO rats. These findings suggest that pancreatic islets may be initial sites that translate the effects of different combinations of dietary carbohydrates and fats into metabolic changes.

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Section: Discussionmentioning

confidence: 56%

Palatinose and oleic acid act together to prevent pancreatic islet disruption in nondiabetic obese Zucker rats

et al. 2008

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“…β-cells slowly divide in adult mice and rats [14], but the process can be accelerated temporarily under physiologic [15]–[17] or pathologic conditions [3], [5], [6]. For instance, β-cell proliferation rates increase during adolescence [18], [19], pregnancy [17], [20], dietary manipulations [15], [21] that may be further stimulated in insulin-resistant states [22] and obesity, during organ regeneration after partial pancreatectomy [7], [23], or following β-cell specific cell-ablation [6]. However, no consensus has emerged regarding the proportional roles played by β-cell mitosis or neogenesis, and what regulates such β-cell expansion in vivo [24].…”

Section: Introductionmentioning

confidence: 99%

Blood Glucose Levels Regulate Pancreatic β-Cell Proliferation during Experimentally-Induced and Spontaneous Autoimmune Diabetes in Mice

et al. 2009

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BackgroundType 1 diabetes mellitus is caused by immune-mediated destruction of pancreatic β-cells leading to insulin deficiency, impaired intermediary metabolism, and elevated blood glucose concentrations. While at autoimmune diabetes onset a limited number of β-cells persist, the cells' regenerative potential and its regulation have remained largely unexplored. Using two mouse autoimmune diabetes models, this study examined the proliferation of pancreatic islet ß-cells and other endocrine and non-endocrine subsets, and the factors regulating that proliferation.Methodology and Principal FindingsWe adapted multi-parameter flow cytometry techniques (including DNA-content measurements and 5′-bromo-2′-deoxyuridine [BrdU] incorporation) to study pancreatic islet single cell suspensions. These studies demonstrate that β-cell proliferation rapidly increases at diabetes onset, and that this proliferation is closely correlated with the diabetic animals' elevated blood glucose levels. For instance, we show that when normoglycemia is restored by exogenous insulin or islet transplantation, the β-cell proliferation rate returns towards low levels found in control animals, yet surges when hyperglycemia recurs. In contrast, other-than-ß endocrine islet cells did not exhibit the same glucose-dependent proliferative responses. Rather, disease-associated alterations of BrdU-incorporation rates of δ-cells (minor decrease), and non-endocrine islet cells (slight increase) were not affected by blood glucose levels, or were inversely related to glycemia control after diabetes onset (α-cells).ConclusionWe conclude that murine β-cells' ability to proliferate in response to metabolic need (i.e. rising blood glucose concentrations) is remarkably well preserved during severe, chronic β-cell autoimmunity. These data suggest that timely control of the destructive immune response after disease manifestation could allow spontaneous regeneration of sufficient β-cell mass to restore normal glucose homeostasis.

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“…In vitro, glucose stimulates β-cell proliferation in fetal and adult rat islets, in mouse islets, and in several rodent insulinoma β-cell lines (3,7,10). In vivo, glucose promotes β-cell proliferation in numerous models, including a high sucrose diet, recovery from hypoglycemia, and partial pancreatectomy (11–14). Alonso et al (15) demonstrated that a 4-day intravenous infusion of 50% glucose into mice, which modestly increases blood glucose concentrations, leads to markedly increased β-cell proliferation as determined by 5-bromo-2′-deoxyuridine (BrdU) incorporation, consistent with earlier rodent infusion studies (16,17).…”

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confidence: 99%

ChREBP Mediates Glucose-Stimulated Pancreatic β-Cell Proliferation

et al. 2012

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Glucose stimulates rodent and human β-cell replication, but the intracellular signaling mechanisms are poorly understood. Carbohydrate response element-binding protein (ChREBP) is a lipogenic glucose-sensing transcription factor with unknown functions in pancreatic β-cells. We tested the hypothesis that ChREBP is required for glucose-stimulated β-cell proliferation. The relative expression of ChREBP was determined in liver and β-cells using quantitative RT-PCR (qRT-PCR), immunoblotting, and immunohistochemistry. Loss- and gain-of-function studies were performed using small interfering RNA and genetic deletion of ChREBP and adenoviral overexpression of ChREBP in rodent and human β-cells. Proliferation was measured by 5-bromo-2′-deoxyuridine incorporation, [3H]thymidine incorporation, and fluorescence-activated cell sorter analysis. In addition, the expression of cell cycle regulatory genes was measured by qRT-PCR and immunoblotting. ChREBP expression was comparable with liver in mouse pancreata and in rat and human islets. Depletion of ChREBP decreased glucose-stimulated proliferation in β-cells isolated from ChREBP−/− mice, in INS-1–derived 832/13 cells, and in primary rat and human β-cells. Furthermore, depletion of ChREBP decreased the glucose-stimulated expression of cell cycle accelerators. Overexpression of ChREBP amplified glucose-stimulated proliferation in rat and human β-cells, with concomitant increases in cyclin gene expression. In conclusion, ChREBP mediates glucose-stimulated proliferation in pancreatic β-cells.

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Mechanisms involved in the beta-cell mass increase induced by chronic sucrose feeding to normal rats

Cited by 19 publications

References 32 publications

Palatinose and oleic acid act together to prevent pancreatic islet disruption in nondiabetic obese Zucker rats

Palatinose and oleic acid act together to prevent pancreatic islet disruption in nondiabetic obese Zucker rats

Blood Glucose Levels Regulate Pancreatic β-Cell Proliferation during Experimentally-Induced and Spontaneous Autoimmune Diabetes in Mice

ChREBP Mediates Glucose-Stimulated Pancreatic β-Cell Proliferation

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