Sex effect on insulin secretion and mitochondrial function in pancreatic beta cells of elderly Wistar rats

Li, Tianyi; Jiao, Wenjun; Li, Weifang; Li, Hua

doi:10.3109/07435800.2015.1124437

Cited by 25 publications

(33 citation statements)

References 52 publications

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“…Moreover, insulin secretion capacity associated with mitochondrial function declines with aging which is a contributing factor to T2D. Evidence showed that elderly male Wistar rats show more significantly decreased mitochondrial function and insulin secretion than elderly females [23], consistent with our results that two mitochondrial function related genes, Cox4i1 and Ndufb7, were identified as downregulated male dependent T2D altered genes.…”

Section: Resultssupporting

confidence: 91%

Mouse Single Islet β Cell Transcriptomics Reveal Sexually Dimorphic Transcriptomes and Type 2 Diabetes Genes

Liu

Zhang

et al. 2020

Preprint

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Type 2 diabetes, characterized by malfunction of pancreatic β cells, is affected by multiple cues including sex differences. Nevertheless, mechanisms of sex differences in type 2 diabetes susceptibility and pathogenesis remain unclear. Using single-cell RNA sequencing (scRNA-seq) technology, we showed that sexual dimorphism of transcriptome exists in mouse β cells. Our analysis further revealed the existence of sex-dependent type 2 diabetes altered genes in high fat diet induced T2D model, suggesting divergences in pathological mechanisms of type 2 diabetes between sexes. Our results indicated that sex should be taken into consideration when treating diabetes, which was further validated by the sex-matched and sex-mismatched islet transplantation in mice. Compared to sex-matched transplants, sex-mismatched transplants showed downregulation of genes involved in the longevity regulating pathway in β cells and led to impaired glucose tolerance in diabetic mice. Taken together, our findings could advance current understanding of type 2 diabetes pathogenesis with sexually dimorphic perspectives and provide new insights to the development of precision medicine.

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Section: Resultssupporting

confidence: 91%

Mouse Single Islet β Cell Transcriptomics Reveal Sexually Dimorphic Transcriptomes and Type 2 Diabetes Genes

Liu

Zhang

et al. 2020

Preprint

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“…In the obese male group (M+HFD), we observed increased insulin and HOMA-IR levels compared with the female obese group, which was in line with another study. 41 In addition, it was shown in another study that insulin resistance is higher among patients with asthma, in line with our results. 42 However, sensitization with OVA after diet-induced obesity caused increased insulin and HOMA-IR levels in the female group when compared with the male group.…”

Section: Discussionsupporting

confidence: 92%

Effect of High-fat Diet on Tracheal Responsiveness to Methacholine and Insulin Resistance Index in Ovalbumin-sensitized Male and Female Rats

Ghobadi

Alipour

Keyhanmanesh

et al. 2019

IJAAI

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Epidemiological and clinical studies have demonstrated a close association between obesity and asthma. The current study investigated the effect of high-fat diet on tracheal responsiveness to methacholine and insulin resistance in ovalbumin (OVA) sensitized male and female rats. The rats were divided into eight groups (n=6 per group): female with the normal diet (F+ND), male with the normal diet (M+ND), female OVA-sensitized with the normal diet (F+SND), male OVA-sensitized with the normal diet (M+SND), female with high-fat diet (F+HFD), male with high-fat diet (M+HFD), female OVA-sensitized with high-fat diet (F+SHFD), and male OVA-sensitized with high-fat diet (M+SHFD). All rats were fed for 8 weeks with high-fat diet or standard pelts, and for another 4 weeks, they were sensitized with OVA or saline. At the end of the study, the tracheal responsiveness to methacholine, serum insulin, and blood glucose levels was measured. Also, insulin resistance indexes were determined. OVA-sensitization and diet-induced obesity caused the curve of methacholine concentration response to shifting to the left. In addition, results indicated that the EC50 (the effective concentration of methacholine generating 50% of peak response) in F+SHFD rats was statistically lower than M+SHFD group (p<0.05). Moreover, insulin resistance was higher in the F+SHFD than the M+SHFD group (p<0.001). These results suggest that insulin resistance and metabolic syndrome may be involved in the pathogenesis of obesity associated with OVA-sensitized rats condition, especially in female animals.

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“…Thus, although male and female mammals exhibit the same overall mechanism of nutrient-induced insulin secretion, the fine-tuning of insulin secretion is regulated in a sex-specific manner by sex hormones. GSIS in rodents declines significantly with age in both sexes [27] , [28] . However, isolated islets from female rats at 18 months of age still show higher glucose-stimulated insulin secretion (GSIS) ex vivo than those of males [27] , confirming results obtained in humans [18] .…”

Section: Sex Differences In β-Cell Function Under Normal and Stress Cmentioning

confidence: 98%

“…GSIS in rodents declines significantly with age in both sexes [27] , [28] . However, isolated islets from female rats at 18 months of age still show higher glucose-stimulated insulin secretion (GSIS) ex vivo than those of males [27] , confirming results obtained in humans [18] . Islets from elderly female rats showed elevated mitochondrial function (ATP content and oxygen consumption) compared with males when exposed to high glucose ex vivo .…”

Section: Sex Differences In β-Cell Function Under Normal and Stress Cmentioning

confidence: 98%

Sex differences underlying pancreatic islet biology and its dysfunction

Gannon

Kulkarni

Tse

et al. 2018

Molecular Metabolism

106

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BackgroundThe sex of an individual affects glucose homeostasis and the pathophysiology, incidence, and prevalence of diabetes as well as the response to therapy.Scope of the reviewThis review focuses on clinical and experimental sex differences in islet cell biology and dysfunction during development and in adulthood in human and animal models. We discuss sex differences in β-cell and α-cell function, heterogeneity, and dysfunction. We cover sex differences in communication between gonads and islets and islet-cell immune interactions. Finally, we discuss sex differences in β-cell programming by nutrition and other environmental factors during pregnancy.Major conclusionsImportant sex differences exist in islet cell function and susceptibility to failure. These differences represent sex-related biological factors that can be harnessed for gender-based prevention of and therapy for diabetes.

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Sex effect on insulin secretion and mitochondrial function in pancreatic beta cells of elderly Wistar rats

Abstract: This study demonstrates a sex dimorphism in the age-associated impairment of pancreatic beta cell function in elderly rats, while the potential mechanism may be related to the sexual differences in mitochondrial biogenesis and function.

Cited by 25 publications

References 52 publications

Mouse Single Islet β Cell Transcriptomics Reveal Sexually Dimorphic Transcriptomes and Type 2 Diabetes Genes

Mouse Single Islet β Cell Transcriptomics Reveal Sexually Dimorphic Transcriptomes and Type 2 Diabetes Genes

Effect of High-fat Diet on Tracheal Responsiveness to Methacholine and Insulin Resistance Index in Ovalbumin-sensitized Male and Female Rats

Sex differences underlying pancreatic islet biology and its dysfunction

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