Excess of glucocorticoids during late gestation impairs the recovery of offspring’s β‐cell function after a postnatal injury

Santos, Cristiane dos; Rafacho, Alex; Ferreira, Sandra Mara; Vettorazzi, Jean Franciesco; Araújo, Thiago dos Reis; Gonçalves, Luciana Mateus; Ruhrmann, Sabrina; Bacos, Karl; Ling, Charlotte; Boschero, Antônio Carlos; Santos, Gustavo Jorge dos

doi:10.1096/fj.202100841r

Cited by 4 publications

(1 citation statement)

References 52 publications

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“…#sc2004; Santa Cruz Biotechnology, Dallas, TX, USA) for 2 h. Insulin-positive cells were detected with 3.3′-diaminobenzidine (Sigma Aldrich, St. Louis, MO, USA) solution. All slides were counterstained with Ehrlich’s hematoxylin and mounted in coverslips using Entellan (Merck, Darmstadt, Germany) [ 78 , 79 ].…”

Section: Methodsmentioning

confidence: 99%

Resistance Training Improves Beta Cell Glucose Sensing and Survival in Diabetic Models

Bronczek

Soares

Marmentini

et al. 2022

IJMS

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Resistance training increases insulin secretion and beta cell function in healthy mice. Here, we explored the effects of resistance training on beta cell glucose sensing and survival by using in vitro and in vivo diabetic models. A pancreatic beta cell line (INS-1E), incubated with serum from trained mice, displayed increased insulin secretion, which could be linked with increased expression of glucose transporter 2 (GLUT2) and glucokinase (GCK). When cells were exposed to pro-inflammatory cytokines (in vitro type 1 diabetes), trained serum preserved both insulin secretion and GCK expression, reduced expression of proteins related to apoptotic pathways, and also protected cells from cytokine-induced apoptosis. Using 8-week-old C57BL/6 mice, turned diabetic by multiple low doses of streptozotocin, we observed that resistance training increased muscle mass and fat deposition, reduced fasting and fed glycemia, and improved glucose tolerance. These findings may be explained by the increased fasting and fed insulinemia, along with increased beta cell mass and beta cell number per islet, observed in diabetic-trained mice compared to diabetic sedentary mice. In conclusion, we believe that resistance training stimulates the release of humoral factors which can turn beta cells more resistant to harmful conditions and improve their response to a glucose stimulus.

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Section: Methodsmentioning

confidence: 99%

Resistance Training Improves Beta Cell Glucose Sensing and Survival in Diabetic Models

Bronczek

Soares

Marmentini

et al. 2022

IJMS

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Calorie restriction increases insulin sensitivity to promote beta cell homeostasis and longevity in mice

dos Santos,

Cambraia,

Shrestha

et al. 2024

Nat Commun

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Caloric restriction (CR) can extend the organism life- and health-span by improving glucose homeostasis. How CR affects the structure-function of pancreatic beta cells remains unknown. We used single nucleus transcriptomics to show that CR increases the expression of genes for beta cell identity, protein processing, and organelle homeostasis. Gene regulatory network analysis reveal that CR activates transcription factors important for beta cell identity and homeostasis, while imaging metabolomics demonstrates that beta cells upon CR are more energetically competent. In fact, high-resolution microscopy show that CR reduces beta cell mitophagy to increase mitochondria mass and the potential for ATP generation. However, CR beta cells have impaired adaptive proliferation in response to high fat diet feeding. Finally, we show that long-term CR delays the onset of beta cell aging hallmarks and promotes cell longevity by reducing beta cell turnover. Therefore, CR could be a feasible approach to preserve compromised beta cell structure-function during aging and diabetes.

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The effect of HNF4α knockout in beta cells is age and gender dependent

Villaca,

Oliveira,

Santos

et al. 2024

Preprint

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HNF4α is important for beta cells’ ability to adequately secrete insulin in response to glucose concentration and endoplasmic reticulum (ER) homeostasis. In humans, HNF4α mutation is responsible for Diabetesmellitussubtype MODY1, which has age determined onset. In addition, in other types of DM, there are evidences that gender can influence beta cell dysfunction, with possible involvement of ER stress pathways. Thus, we assessed the influence of gender and age on beta cell dysfunction induced by HNF4α absence. We used an animal model with specific beta cells KO for HNF4α, induced after birth (Ins. CRE HNF4αloxP/loxP). Glucose intolerance is observed after 10 days of KO induction, at 50 days of age, with KO males (MKO) showing greater glucose intolerance than KO females (FKO). Percentage of insulin-positive cells in KO mice islets is lower compared to Control at all ages evaluated, with MKO having a lower percentage at later ages compared to FKO. Both KO groups have reduced beta cell mass and increased α-cell mass, which is higher in MKO. ER stress is induced in both KO groups. However, ER stress-mediated apoptosis is observed only in MKO. FKO shows evidence of beta cell differentiated state loss. Thus, loss of beta cells in HNF4α KO is influenced by gender and age, involves induction of ER stress, and is more pronounced in males, where ER stress-induced beta cell death is observed. Partial protection observed in females seems to involve dedifferentiation of beta cells.

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Excess of glucocorticoids during late gestation impairs the recovery of offspring’s β‐cell function after a postnatal injury

Cited by 4 publications

References 52 publications

Resistance Training Improves Beta Cell Glucose Sensing and Survival in Diabetic Models

Resistance Training Improves Beta Cell Glucose Sensing and Survival in Diabetic Models

Calorie restriction increases insulin sensitivity to promote beta cell homeostasis and longevity in mice

The effect of HNF4α knockout in beta cells is age and gender dependent

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