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1.
Ageing Res Rev ; 80: 101674, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35724861

RESUMO

The prevalence of type 2 diabetes (T2D) and impaired glucose tolerance (IGT) increases with ageing. T2D generally results from progressive impairment of the pancreatic islets to adapt ß-cell mass and function in the setting of insulin resistance and increased insulin demand. Several studies have shown an age-related decline in peripheral insulin sensitivity. However, a precise understanding of the pancreatic ß-cell response in ageing is still lacking. In this review, we summarize the age-related alterations, adaptations and/or failures of ß-cells at the molecular, morphological and functional levels in mouse and human. Age-associated alterations include processes such as ß-cell proliferation, apoptosis and cell identity that can influence ß-cell mass. Age-related changes also affect ß-cell function at distinct steps including electrical activity, Ca2+ signaling and insulin secretion, among others. We will consider the potential impact of these alterations and those mediated by senescence pathways on ß-cells and their implications in age-related T2D. Finally, given the great diversity of results in the field of ß-cell ageing, we will discuss the sources of this heterogeneity. A better understanding of ß-cell biology during ageing, particularly at older ages, will improve our insight into the contribution of ß-cells to age-associated T2D and may boost new therapeutic strategies.


Assuntos
Diabetes Mellitus Tipo 2 , Resistência à Insulina , Células Secretoras de Insulina , Envelhecimento/metabolismo , Animais , Diabetes Mellitus Tipo 2/metabolismo , Humanos , Insulina/metabolismo , Secreção de Insulina , Células Secretoras de Insulina/metabolismo , Camundongos
2.
J Gerontol A Biol Sci Med Sci ; 77(3): 405-415, 2022 03 03.
Artigo em Inglês | MEDLINE | ID: mdl-34562079

RESUMO

Aging is associated with a decline in peripheral insulin sensitivity and an increased risk of impaired glucose tolerance and type 2 diabetes. During conditions of reduced insulin sensitivity, pancreatic ß cells undergo adaptive responses to increase insulin secretion and maintain euglycemia. However, the existence and nature of ß-cell adaptations and/or alterations during aging are still a matter of debate. In this study, we investigated the effects of aging on ß-cell function from control (3-month-old) and aged (20-month-old) mice. Aged animals were further categorized into 2 groups: high insulin sensitive (aged-HIS) and low insulin sensitive (aged-LIS). Aged-LIS mice were hyperinsulinemic, glucose intolerant, and displayed impaired glucose-stimulated insulin and C-peptide secretion, whereas aged-HIS animals showed characteristics in glucose homeostasis similar to controls. In isolated ß cells, we observed that glucose-induced inhibition of KATP channel activity was reduced with aging, particularly in the aged-LIS group. Glucose-induced islet NAD(P)H production was decreased in aged mice, suggesting impaired mitochondrial function. In contrast, voltage-gated Ca2+ currents were higher in aged-LIS ß cells, and pancreatic islets of both aged groups displayed increased glucose-induced Ca2+ signaling and augmented insulin secretion compared with controls. Morphological analysis of pancreas sections also revealed augmented ß-cell mass with aging, especially in the aged-LIS group, as well as ultrastructural ß-cell changes. Altogether, these findings indicate that aged mouse ß cells compensate for the aging-induced alterations in the stimulus-secretion coupling, particularly by adjusting their Ca2+ influx to ensure insulin secretion. These results also suggest that decreased peripheral insulin sensitivity exacerbates the effects of aging on ß cells.


Assuntos
Diabetes Mellitus Tipo 2 , Resistência à Insulina , Células Secretoras de Insulina , Ilhotas Pancreáticas , Envelhecimento , Animais , Cálcio , Glucose , Insulina/farmacologia , Ilhotas Pancreáticas/fisiologia , Masculino , Camundongos
3.
Arch Virol ; 162(4): 1037-1041, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28005211

RESUMO

Viral hemorrhagic septicemia virus (VHSV) and infectious pancreatic necrosis virus (IPNV) are economically important pathogens of the salmonid aquaculture industry. In previous work we demonstrated that a cell line persistently infected with IPNV (EPCIPNV) exhibited antiviral activity against superinfection with the heterologous virus VHSV. This work extends our study by analyzing the replication of VHSV in the IPNV-persistently infected cells. At early and late stages of infection VHSV RNA synthesis, as well as VHSV-induced syncytia formation, were examined in EPCIPNV cultures. During the course of VHSV infection the accumulation of VHSV RNA is inhibited in EPCIPNV cells. Typical VHSV-induced membrane fusion at the late stages of infection is also absent in the IPNV carrier cultures. VHSV binding and fusion to EPCIPNV cells did not appear to be impaired, but a potent inhibitory effect on VHSV RNA synthesis is exerted at early times of infection in the IPNV carrier culture. In conclusion, the EPCIPNV cells are considered to be a useful system to study viral interference as well to analyze the mechanisms underlying the phenomenon of superinfection exclusion.


Assuntos
Doenças dos Peixes/virologia , Vírus da Necrose Pancreática Infecciosa/fisiologia , Novirhabdovirus/fisiologia , Infecções por Rhabdoviridae/veterinária , Replicação Viral , Animais , Técnicas de Cultura de Células , Linhagem Celular , Vírus da Necrose Pancreática Infecciosa/genética , Vírus da Necrose Pancreática Infecciosa/crescimento & desenvolvimento , Novirhabdovirus/genética , Novirhabdovirus/crescimento & desenvolvimento , Infecções por Rhabdoviridae/virologia , Salmonidae/virologia , Cultura de Vírus
4.
Fish Shellfish Immunol ; 58: 483-489, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27693199

RESUMO

IPNV is a salmonid birnavirus that possesses the ability to establish asymptomatic persistent infections in a number of valuable fish species. The presence of IPNV may interfere with subsequent infection by other viruses. In the present study we show that an IPNV-carrier cell line (EPCIPNV) can induce an antiviral state in fresh EPC by co-cultivating both cell types in three different ways: a "droplet" culture system, a plastic chamber setup, and a transmembrane (Transwell®) system. All three cell co-culture methods were proven useful to study donor/target cell interaction. Naïve EPC cells grown in contact with EPCIPNV cells develop resistance to VHSV superinfection. The transmembrane system seems best suited to examine gene expression in donor and target cells separately. Our findings point to the conclusion that one or more soluble factors produced by the IPNV carrier culture induce the innate immune response within the target cells. This antiviral response is associated to the up-regulation of interferon (ifn) and mx gene expression in target EPC cells. To our knowledge this is the first article describing co-culture systems to study the interplay between virus-carrier cells and naive cells in fish.


Assuntos
Infecções por Birnaviridae/veterinária , Cyprinidae , Doenças dos Peixes/imunologia , Vírus da Necrose Pancreática Infecciosa/fisiologia , Interferência Viral , Animais , Infecções por Birnaviridae/imunologia , Infecções por Birnaviridae/virologia , Linhagem Celular , Técnicas de Cocultura/veterinária , Doenças dos Peixes/virologia
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