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In the short term, glucose homeostasis increases, but long-term fasting during adolescence can impair beta-cell maturation.
study: Chronic intermittent fasting impairs beta cell maturation and function in adolescent mice. Image credit: pormezz/shutterstock.com
In a recent study published in Cell Reports, researchers demonstrated that long-term (LT) intermittent fasting (IF) impairs beta-cell function and maturation in adolescent mice.
background
Overconsumption of good-tasting, energy-rich foods characterizes modern eating habits. It is a diet strategy that alternates between meals and fasting periods, and has gained considerable popularity in recent years.
Studies suggest that at least 10 hours of fasting windows and the remaining time of the meal period is essential for metabolic benefits.
Most cases where strategies have beneficial effects on metabolic parameters in mice and humans, such as blood pressure, weight, cholesterol, insulin sensitivity, and longevity.
In the context of type 2 diabetes (T2D), increased insulin synthesis and expression of secreted genes improve β-cell function and increase insulin levels. However, the effect of IF on T1D is unknown.
Research and findings
In this study, researchers investigated the effects of mice IF at different life stages. First, they assessed the effects of 5 weeks (short-term, ST) and 10 weeks (LT) for food intake and weight in younger (2 months), middle-aged (8 months old), and older (18 months old) mice. Also included were age-matched controls supplied to Ad Libitum.
Middle-aged and older mice showed no changes in body weight at ST.
Conversely, LT is when weight loss in all groups, regardless of age. Insulin (ITTS) and glucose tolerance tests (GTT) showed ST when insulin sensitivity and glucose homeostasis were enhanced independent of age.
In contrast, GTT improved with LT in older mice, but ITT was not different from controls. Furthermore, ITT and GTT were improved in middle-aged mice after IF, but there was no difference between the intervention and control groups of young mice.
Additionally, glucose-stimulated insulin secretion (GSIS) tests were performed to examine β-cell function in isolated primary islets. Control and LT islands when groups secrete similar levels of insulin at low glucose concentrations.
In contrast, if more insulin was secreted than insulin from high glucose concentrations, the islets of older mice in LT. Moreover, there were no major changes in the islets from middle-aged mice. Conversely, if the GSI is lower than the control, younger mice in LT.
Older LT mice had no change in the amount of islands, but less in other age groups. Furthermore, insulin content in isolated islets was increased in older mice, not changed in middle-aged mice, but decreased in younger mice with LT-IF.
These findings suggest that LT improves ex in vivo islet function in older mice in cases of islet dysfunction in young mice. Furthermore, single-cell RNA sequencing (SCRNA-seq) was performed in isolated islets of all age groups following LT IF. Cell clusters were assigned to major endocrine cell types based on established markers, glucagon, pancreatic polypeptides, insulin, and somatostatin.
Additionally, bioinformatic analysis of β cells was performed to confirm IF and age-dependent transcriptome responses.
This revealed that the β-cell mature gene set differed most significantly between the IF of LT and the control group. Middle-aged and older mice had higher β-cell maturation scores than controls, whereas younger mice had lower scores.
The team analyzed overexpression of differentially regulated gene pathways in β-cells and identified clusters of related pathways, including insulin function and T2D groups. We then leveraged overlaps of genes annotated for β-cell maturation and used those that contributed to pathway overexpression to identify potential candidate genes.
They found that most candidate genes, including insulin 1 (INS1), solute carrier family 2 member 2 (SLC2A2), and MAF BZIP transcription factor A (MAFA), were only low in young mice exposed to LT.
Finally, the team analyzed bulk RNA-SEQ datasets of human islets from donors of T1D or T2D. We noted that when samples from T1D patients had similar downregulation patterns, the genes were downregulated in younger mice with LT.
Conclusion
In short, this study showed that LT exhibited LT when ST offers metabolic benefits in mice across age groups but adversely affects β-cell function in younger mice.
SCRNA-seq revealed transcriptional profiles associated with β-cell maturation disorder in young mice. This was associated with transcriptional signatures and maturation-related genes of β-cell function in T1D patients.
Overall, these findings suggest that we consider whether there is a period of younger people as they may exacerbate the outcome of diabetes.
