Quick-term IF boosts glucose homeostasis, however extended fasting in adolescence could impair β cell maturation—probably linking persistent IF to sort 1 diabetes danger.
Examine: Persistent intermittent fasting impairs β cell maturation and performance in adolescent mice. Picture Credit score: Pormezz/Shutterstock.com
In a latest research revealed in Cell Stories, researchers demonstrated that long-term (LT) intermittent fasting (IF) impairs β cell perform and maturation in adolescent mice.
Background
An overconsumption of palatable and energy-rich meals characterizes fashionable dietary habits. IF is a dietary technique of alternating between durations of consuming and fasting and has gained appreciable recognition in recent times.
Research recommend {that a} fasting window of not less than 10 hours, adopted by an consuming interval for the remainder of the day, is crucial for metabolic advantages.
Most IF methods have useful results on metabolic parameters in mice and people, together with blood stress, physique weight, ldl cholesterol, insulin sensitivity, and life span.
Within the context of sort 2 diabetes (T2D), IF results in greater insulin synthesis and secretion gene expression, improved β cell perform, and better insulin ranges. Nonetheless, the influence of IF on T1D is unclear.
The research and findings
Within the current research, researchers examined the results of IF in mice at totally different life levels. First, they evaluated the influence of five-week (short-term, ST) and 10-week (LT) IF on meals consumption and physique weight in younger (two-month-old), middle-aged (eight-month-old), and outdated (18-month-old) mice. In addition they included age-matched controls fed advert libitum.
Center-aged and outdated mice exhibited no physique weight modifications with ST IF, whereas the younger group had decrease physique weights resulting from diminished meals consumption relative to controls.
Conversely, LT IF led to decrease physique weights in all teams, no matter age. Insulin (ITTs) and glucose tolerance checks (GTTs) confirmed that ST IF augmented insulin sensitivity and glucose homeostasis unbiased of age.
Against this, GTT improved with LT IF in outdated mice, whereas ITT didn’t differ from controls. Additional, ITTs and GTTs had been improved in middle-aged mice after LT IF, whereas they weren’t totally different between the intervention and management teams of younger mice.
Additional, glucose-stimulated insulin secretion (GSIS) checks had been carried out to look at β cell perform in remoted major islets. Islets from management and LT IF teams secreted related ranges of insulin at low glucose concentrations.
Against this, islets from outdated mice on LT IF secreted extra insulin than these from controls at excessive glucose concentrations. Apart from, there have been no important modifications in islets from middle-aged mice. Conversely, younger mice on LT IF had decrease GSIS than controls.
Outdated mice on LT IF had no modifications in islet amount, however the different age teams had decrease portions. Additional, insulin content material in remoted islets was elevated in outdated mice, unchanged in middle-aged mice, and diminished in younger mice on LT-IF.
These findings steered that LT IF impaired islet perform in younger mice and improved ex vivo islet perform in outdated mice. Additional, single-cell RNA sequencing (scRNA-seq) was carried out on remoted islets from all age teams following LT IF. Cell clusters had been assigned to main endocrine cell sorts based mostly on established markers: glucagon, pancreatic polypeptide, insulin, and somatostatin.
As well as, bioinformatic analyses of β cells had been carried out to establish IF- and age-dependent transcriptomic responses.
This revealed that the β cell maturation gene set was probably the most considerably totally different between LT IF and management teams. Center-aged and outdated mice had greater β cell maturation scores than controls, whereas the younger mice had decrease scores.
The crew analyzed the over-representation of pathways in differentially regulated genes in β cells and recognized a cluster of associated pathways, together with these of insulin perform and T2D. Subsequent, they leveraged the overlap of genes annotated to β cell maturation with these contributing to pathway over-representation to determine potential candidate genes.
They discovered that almost all candidate genes, together with insulin 1 (Ins1), solute service household two member 2 (Slc2a2), and MAF BZIP transcription issue A (Mafa), had been solely decrease in younger mice uncovered to LT IF.
Lastly, the crew analyzed bulk RNA-seq datasets of human islets from donors with T1D or T2D. It famous that the genes downregulated in younger mice on LT IF had an analogous downregulation sample in samples from T1D sufferers.
Conclusions
In sum, the research illustrated that ST IF resulted in metabolic advantages in mice throughout age teams, however LT IF negatively affected β cell perform in younger mice.
scRNA-seq revealed a transcriptional profile related to impaired β cell maturation in younger mice, which was linked to the transcriptional signature of β cell perform and maturation-related genes in T1D sufferers.
Total, these findings recommend contemplating IF length in youthful individuals, as it could irritate diabetes outcomes.
