Reduced pancreatic β-cell mass is associated with decreased FoxO1 and Erk1/2 protein phosphorylation in low-protein malnourished rats

Rafacho, Alex; Giozzet, Vanessa Aparecida; Boschero, Antônio Carlos; Abrantes, Julia Laura Fernandes; Cestari, Tânia Mary; Carneiro, Everardo M.; Bosqueiro, José Roberto

doi:10.1590/s0100-879x2009001000010

Cited by 16 publications

(17 citation statements)

References 42 publications

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“…FoxO1 was shown to modulate antioxidant enzymes mRNA content (Golson & Kaestner, ). These results corroborate with our data, where reduced beta cell mass was accompanied by increased catalase expression, probably as consequence of decreased FoxO1 phosphorylation in LP rats, leading to the higher mRNA levels of that antioxidant enzyme (Rafacho, Giozzet, et al, ).…”

Section: Discussionsupporting

confidence: 93%

“…Most of our results agree with previous reports, showing altered SOD and CAT mRNA and activities, whereas the same variables regarding GPx remained relatively unaltered in post‐weaning protein malnutrition. Reduced beta cell mass in LP adult rats was documented by Rafacho, Giozzet, et al (), Swenne et al (), and Tse et al (), suggesting decreased beta cell mass regulation by LP diets. We believe that reduced beta cell mass could be involved with oxidative stress in LP rats.…”

Section: Discussionmentioning

confidence: 74%

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Reduced glucose‐induced insulin secretion in low‐protein‐fed rats is associated with altered pancreatic islets redox status

Cappelli

Zoppi

Silveira

et al. 2017

Journal Cellular Physiology

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In the present study, we investigated the relationship between early life protein malnutritioninduced redox imbalance, and reduced glucose-stimulated insulin secretion. After weaning, male Wistar rats were submitted to a normal-protein-diet (17%-protein, NP) or to a low-protein-diet (6%-protein, LP) for 60 days. Pancreatic islets were isolated and hydrogen peroxide (H 2 O 2 ), oxidized (GSSG) and reduced (GSH) glutathione content, CuZn-superoxide dismutase (SOD1), glutathione peroxidase (GPx1) and catalase (CAT) gene expression, as well as enzymatic antioxidant activities were quantified. Islets that were pre-incubated with H 2 O 2 and/or N-acetylcysteine, were subsequently incubated with glucose for insulin secretion measurement.Protein malnutrition increased CAT mRNA content by 100%. LP group SOD1 and CAT activities were 50% increased and reduced, respectively. H 2 O 2 production was more than 50% increased whereas GSH/GSSG ratio was near 60% lower in LP group. Insulin secretion was, in most conditions, approximately 50% lower in LP rat islets. When islets were pre-incubated with H 2 O 2 (100 μM), and incubated with glucose (33 mM), LP rats showed significant decrease of insulin secretion. This effect was attenuated when LP islets were exposed to N-acetylcysteine. K E Y W O R D Santioxidant enzymes, insulin secretion, pancreatic islets, protein malnutrition, reactive oxygen species | INTRODUCTIONInsulin release is known to be tightly coupled to ATP production.Briefly, the canonical theory of glucose-induced insulin secretion (GIIS) states that when blood glucose rises, islet β-cells stimulate ATP synthesis. ATP acts on ATP-dependent K + channels leading to membrane depolarization. This process is followed by opening of voltage-sensitive calcium channels; increasing cytosolic Ca 2+ concentration and, consequently, insulin exocytosis (Aguilar-Bryan et al., 1995).Although not yet fully understood, the discovery of ATP-independent K + channels mechanisms gave rise to several speculations about how glucose metabolism could regulate GIIS in addition to the solely ATP enhancement effect (Szollosi, Nenquin, Aguilar-Bryan, Bryan, & Henquin, 2007

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 74%

Reduced glucose‐induced insulin secretion in low‐protein‐fed rats is associated with altered pancreatic islets redox status

Cappelli

Zoppi

Silveira

et al. 2017

Journal Cellular Physiology

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“…We and other groups have previously demonstrated that rodents subjected to LP diet exhibit changes in ␤-cell mass as well as altered GSIS that leads to reduced insulin secretion (9,10,12,13,38). Despite lower plasma insulin levels, LP rodents have enhanced peripheral insulin sensitivity, which may allow for the normoglycemic state found in these animals (12,13,38,39).…”

Section: Discussionmentioning

confidence: 95%

Functional and Structural Adaptations in the Pancreatic α-Cell and Changes in Glucagon Signaling During Protein Malnutrition

et al. 2012

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Chronic malnutrition leads to multiple changes in β-cell function and peripheral insulin actions to adapt glucose homeostasis to these restricted conditions. However, despite glucose homeostasis also depends on glucagon effects, the role of α-cells in malnutrition is largely unknown. Here, we studied α-cell function and hepatic glucagon signaling in mice fed with low-protein (LP) or normal-protein diet for 8 wk after weaning. Using confocal microscopy, we found that inhibition of Ca²⁺ signaling by glucose was impaired in α-cells of LP mice. Consistent with these findings, the ability of glucose to inhibit glucagon release in isolated islets was also diminished in LP mice. This altered secretion was not related with changes in either glucagon gene expression or glucagon content. A morphometric analysis showed that α-cell mass was significantly increased in malnourished animals, aspect that was probably related with their enhanced plasma glucagon levels. When we analyzed the hepatic function, we observed that the phosphorylation of protein kinase A and cAMP response-binding element protein in response to fasting or exogenous glucagon was impaired in LP mice. Additionally, the up-regulated gene expression in response to fasting observed in the hepatic glucagon receptor as well as several key hepatic enzymes, such as peroxisome proliferator-activated receptor γ, glucose-6-phosphatase, and phosphoenolpyruvate carboxykinase, was altered in malnourished animals. Finally, liver glycogen mobilization in response to fasting and the ability of exogenous glucagon to raise plasma glucose levels were lower in LP mice. Therefore, chronic protein malnutrition leads to several alterations in both the α-cell function and hepatic glucagon signaling.

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“…Results Odds ratios were estimated using multivariate logistic regression models. For example, several experimental studies in animals have showed that proteincalorie malnutrition and magnesium deficiency cause low insulin secretion [19,20]. Model 2, adjusted for age, sex, marital status, education, smoking status, alcohol consumption and fruit and ⁄ or vegetable intake.…”

Section: Discussionmentioning

confidence: 99%

“…It has been suggested that the association between underweight and increased risk of diabetes may be attributable to declines in insulin secretion. For example, several experimental studies in animals have showed that proteincalorie malnutrition and magnesium deficiency cause low insulin secretion [19,20]. Studies in humans have also observed that subjects with poor nutrition status (assessed by a decrease in serum albumin concentration and low dietary magnesium) were associated with an increased prevalence of diabetes [21,22].…”

Section: Discussionmentioning

confidence: 99%

Global variability in diabetes mellitus and its association with body weight and primary healthcare support in 49 low‐ and middle‐income developing countries

2012

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Reduced pancreatic β-cell mass is associated with decreased FoxO1 and Erk1/2 protein phosphorylation in low-protein malnourished rats

Cited by 16 publications

References 42 publications

Reduced glucose‐induced insulin secretion in low‐protein‐fed rats is associated with altered pancreatic islets redox status

Reduced glucose‐induced insulin secretion in low‐protein‐fed rats is associated with altered pancreatic islets redox status

Functional and Structural Adaptations in the Pancreatic α-Cell and Changes in Glucagon Signaling During Protein Malnutrition

Global variability in diabetes mellitus and its association with body weight and primary healthcare support in 49 low‐ and middle‐income developing countries

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