Search Results (987)

Background: Alcohol use disorder (AUD) is associated with chronic heavy or repeated binge alcohol abuse, which can cause alcohol-related brain damage (ARBD) marked by neurobehavioral, cognitive, and motor deficits. The anterior frontal lobe and cerebellar vermis are two of the major targets of ARBD in humans with AUD and in experimental alcohol exposed models. Alcohol’s neurotoxic and neurodegenerative effects include impairments in signaling through insulin and insulin-like growth factor (IGF) pathways that regulate energy metabolism. This human AUD study was inspired by a recent report suggesting that dysfunction of the frontal lobe incretin network in experimental ARBD is linked to known impairments in brain insulin/IGF signaling. Objective: The overarching goal was to investigate whether AUD is associated with dysfunction of the brain’s incretin network, focusing on the cerebellum and frontal lobe. Methods: Fresh frozen postmortem cerebellar vermis and anterior frontal lobe tissues from adult male AUD (n = 6) and control (n = 6) donors were processed for protein extraction. Duplex enzyme-linked immunosorbent assays (ELISAs) were used to assess immunoreactivity to neurofilament light chain (NfL) as a marker of neurodegeneration. A multiplex ELISA was used to measure immunoreactivity to a panel of gut hormones, including incretin polypeptides. Results: AUD was associated with significantly increased NfL immunoreactivity in both the cerebellar vermis and anterior frontal lobe. However, the patterns of AUD-related alterations in gut hormone immunoreactivity differed regionally. AUD reduced pancreatic polypeptide immunoreactivity in the cerebellar vermis, and GIP, GLP-1, leptin, and ghrelin in the frontal lobe. Conclusions: (1) Increased NfL may serve as a useful biomarker of neurodegeneration in AUD. (2) AUD’s adverse effects on neuroendocrine signaling networks differ in the cerebellar vermis and anterior frontal region, although both are significant targets of ARBD. (3) The finding of AUD-associated reductions in frontal lobe GIP and GLP-1 suggests that therapeutic targeting with incretin receptor agonists may help restore energy metabolism and neurobehavioral and cognitive functions linked to their networks. Full article

Background and Objectives: Periodontal disease, characterized by progressive destruction of tooth-supporting tissues, often results in substantial alveolar bone loss, necessitating regenerative interventions such as guided bone regeneration (GBR). Insulin-like growth factor 2 (IGF-2) has emerged as a promising biomolecule for periodontal regeneration because of its osteogenic and immunomodulatory properties. Materials and Methods: A comprehensive literature search was conducted across five electronic databases (Scopus, ScienceDirect, PubMed, Wiley, and EBSCO). Studies examining the use of IGF-2 in periodontal or alveolar bone regeneration, including randomized controlled trials, animal studies, and in vitro experiments, were included. Results: Three studies met the inclusion criteria. In vitro, IGF-2 was associated with enhanced osteogenic differentiation and mineralization of mesenchymal stem cells, along with upregulation of key osteogenic markers. In animal models, IGF-2 treatment was associated with increased osteogenesis, greater bone volume, and a shift in macrophage polarization toward a less inflammatory phenotype. However, heterogeneity in study designs, protocols, and outcome measures limited direct comparisons. Conclusions: In vitro, IGF-2 was associated with enhanced osteogenic differentiation and mineralization of mesenchymal stem cells, accompanied by upregulation of key osteogenic markers. In animal models, IGF-2 treatment was associated with increased osteogenesis, greater bone volume, and a shift in macrophage polarization toward a less inflammatory phenotype. Full article

The insulin-like growth factor (IGF) axis orchestrates hepatic development, regeneration, and metabolism, yet the roles of individual IGF-binding proteins (IGFBPs) remain incompletely defined. IGFBP-6, a high-affinity, IGF-II-preferring binding protein, has emerged as a context-dependent modulator of IGF bioavailability and cell signaling with additional IGF-independent actions. This review synthesizes current evidence on IGFBP-6 in liver biology and disease. We first outline hepatic expression, regulation, and post-translational processing of IGFBP-6 across development, homeostasis, and injury, and summarize its effects on canonical IGF-II/IGF1R signaling and downstream phosphatidylinositol 3-kinase—protein kinase B (PI3K–AKT) and rat sarcoma—mitogen-activated protein kinase (RAS–MAPK) pathways. We then evaluate experimental and clinical data linking IGFBP-6 to steatotic liver disease, inflammation, and fibrogenesis, including putative roles in hepatocyte stress responses, stellate cell activation, and extracellular matrix remodeling. Finally, we examine IGFBP-6 in primary liver cancers—hepatocellular carcinoma and cholangiocarcinoma—highlighting evidence for tumor-suppressive versus pro-migratory activities, potential crosstalk with hypoxia, Wnt/β-catenin and TGF-β signaling, and interactions with the tumor immune microenvironment. Across conditions, we assess the translational potential of IGFBP-6 as a circulating or tissue biomarker, its utility for patient stratification, and prospects for therapeutic targeting—either by modulating IGF-II sequestration or exploiting IGF-independent mechanisms. We conclude by identifying key knowledge gaps, methodological limitations, and priorities for future studies, including standardized measurement, cell-type-resolved profiling, and in vivo perturbation in clinically relevant models. Collectively, the review positions IGFBP-6 as a nuanced regulator of liver pathophysiology and a promising, yet underexplored, lever for diagnosis and therapy. Full article

Oocyte-granulosa cell complexes (OGCs) cultivation is crucial for advancing reproductive biotechnology but remains incomplete and needs further optimization. Insulin-like growth factor-I (IGF-I) regulates granulosa cell proliferation and apoptosis, and numerous studies have confirmed its role in promoting ovarian follicle development. Porcine follicular fluid (PFF) contains factors beneficial for oocyte growth, which may enhance oocyte development. To investigate whether IGF-I and PFF improve the in vitro culture efficiency of porcine OGCs, we cultured OGCs with IGF-I (0, 10, 50, 100 ng/mL) and PFF (from 3 to 6 mm follicles) at concentrations of 0, 2.5%, 5%, 10%, respectively. The results revealed that 50 and 100 ng/mL IGF-I significantly increased the antrum formation rate of OGCs (from 61.11 ± 7.35% to 88.89 ± 7.35%) and diameter growth of oocytes (from 108.77 ± 0.27 µm to 114.94 ± 0.58 and 113.29 ± 0.50 µm, respectively). However, only the 50 ng/mL group, but not the 100 ng/mL group, significantly improved the maturation rate (38.13 ± 3.77% vs. 25.00 ± 3.27%, p < 0.05) of oocytes. Additionally, 50 ng/mL IGF-I downregulated BAX (a pro-apoptotic gene) and upregulated BCL-2 (an anti-apoptotic factor) in granulosa cells, ultimately reducing apoptosis. In contrast, none of the PFF doses used in this study induced the formation of enclosed antrum-like structures in OGCs, nor did they significantly enhance their in vitro development. Our findings demonstrate that 50 ng/mL IGF-I effectively promotes the in vitro growth of porcine early antral follicle-derived OGCs by reducing apoptosis, whereas tested PFF concentrations had no beneficial effects and induced abnormal granulosa cell growth. How PFF modulates the adherent and spreading growth of granulosa cells has not been fully elucidated and requires further clarification. Full article

Insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) is an RNA-binding protein known to play critical roles in metabolism, cell proliferation, and tumorigenesis. Although its involvement in muscle development has been documented in several species, the function of goose IGF2BP2 remains largely unexplored. In this study, we cloned and characterized the full-length cDNA and genomic DNA sequences of goose IGF2BP2. The cDNA is 2957 bp in length and contains a 1662 bp open reading frame encoding a 553-amino acid protein with five conserved RNA-binding domains. The genomic sequence spans 12,183 bp and consists of 12 exons and 11 introns. A total of 60 genetic variants were identified, including a deletion of a G base at position 2299 (g.2299delG) that results in a frameshift mutation. Expression analysis revealed high levels of IGF2BP2 mRNA in the liver, heart, and muscle tissues of female geese across embryonic (E25d), growing (A70d), and laying (L270d) stages, consistent with a potential role in muscle development (p < 0.05). Functionally, overexpression of IGF2BP2 in skeletal muscle satellite cells (SMSCs) was associated with significant changes in the expression of several genes linked to muscle development and signaling pathways, including upregulation of IGF1, EGFR, FGF19, BMP6, BMP2, ACVR1C and WNT5A and downregulation of MYBPC3, NODAL, HOXD13, TNXB, and ADD2 (Padj < 0.01). Furthermore, protein–protein interaction (PPI) network analysis of these genes suggests that IGF2BP2 may coordinate key genes, contributing to its potential role in skeletal muscle development in geese. Full article

Background: The insulin-like growth factor 2 receptor (IGF-2R), also known as the cation-independent mannose 6-phosphate receptor (CI-M6PR), is emerging as a critical receptor for brain function and disease. IGF-2R, in fact, plays a key role in long-term memory, and its activation by several ligands shows beneficial effects in multiple neurodevelopmental and neurodegenerative disease models. Thus, its targeting is very promising for neuropsychiatric therapeutic interventions. IGF-2R’s main known functions are transport of lysosomal enzymes and regulation of developmental tissue growth, but in the brain, it also controls learning-dependent protein synthesis underlying long-term memory. However, little is known about this receptor in brain cells, including its cell-type-specific and subcellular expression. Methods: We conducted a comprehensive investigation to comparatively assess IGF-2R protein levels in different brain cell types across various brain regions in adult male C57BL/6J mice using dual and multiplex immunofluorescent staining with cell-type-specific markers. The IGF-2R protein distribution was also compared with Igf2r mRNA expression in publicly available single-cell RNA sequencing databases. Results: A ranking of IGF-2R levels in the soma of various cell types in the hippocampus and cortical regions revealed that the highest enrichment is, by far, in excitatory and inhibitory neurons, followed by vascular mural cells and subpopulations of oligodendrocyte lineage cells, with low to undetectable levels in astrocytes, microglia, vascular endothelial cells, and perivascular fibroblasts. High levels of IGF-2R were also found in ependymal cells, choroid plexus epithelial cells, and a subpopulation of meningeal fibroblast-like cells. IGF-2R was found in dendritic and putative axonal compartments throughout the brain, with particularly high levels in the stratum lucidum. The receptor’s protein distribution aligned with that of the mRNA in mouse brain databases. Conclusions: These results suggest that IGF-2R-mediated functions in the brain vary across different cell types and subcellular compartments, with the most active roles in specific subpopulations of neurons, mural cells, ependymal cells, meningeal cells, and cells of the oligodendrocyte lineage. This study advances our understanding of IGF-2R’s distribution in the brain, which is essential for formulating new hypotheses about its functions and therapeutic targeting. Full article

Age-associated hair loss is primarily driven by decreased function and proliferation of hair follicle stem cells (HFSCs), often exacerbated by increased inhibitory signaling and changes in the stem cell niche. Macrophage polarization to the anti-inflammatory M2 phenotype is known to increase stem cell proliferation. We investigated the effects of poly-D,L-lactic acid (PDLLA) on hair growth in middle-aged skin, focusing on its role in modulating macrophage polarization and HFSC activity. Senescent macrophages were analyzed for Piezo1 activity, macrophage polarization, and secretion of hepatocyte growth factor (HGF) and insulin-like growth factor-1 (IGF-1) after PDLLA treatment. Downstream effects on HFSC proliferation, stemness, and Wnt signaling were assessed, including inhibition experiments using the Piezo1 blocker GsMTx4. In vivo analyses assessed hair follicle number, diameter, length, anagen duration, and hair coverage following PDLLA administration in middle-aged mice. PDLLA increased Piezo1 expression and activity in senescent macrophages, enhancing M2 polarization and secretion of HGF and IGF-1. This activated the RAS/ERK signaling pathway, promoting HFSC proliferation and stemness. Furthermore, PDLLA upregulated Wnt signaling molecules (Wnt3a, Wnt10b, and β-catenin) and anagen phase-related factor (Axin2, LEF1, and Lgr5), which were decreased by GsMTX4. In middle-aged animal skin, PDLLA administration led to increased hair follicle number, diameter, and length, as well as prolonged anagen and greater hair coverage. Collectively, these findings suggest that PDLLA rejuvenates the middle-aged skin microenvironment, at least in part through Piezo1-associated M2 macrophage polarization and enhanced HFSC function, offering a promising therapeutic strategy for age-related hair loss targeting both the immune and the stem cell compartments. Full article

Linear growth is traditionally attributed to the growth hormone (GH)/insulin-like growth factor-1 (IGF-1) axis, yet “growth without GH” is documented. We report five patients with severe GH deficiency—one congenital and four acquired, who reached normal or tall stature despite persistently low IGF-1. All patients had obesity and metabolic complications (insulin resistance, dyslipidemia, and/or fatty liver). Catch-up or sustained growth occurred before or independent of sex-steroid replacement in most cases. One patient with lifelong hypogonadism showed slow, prolonged growth with delayed epiphyseal fusion. Three patients also received recombinant human GH (rhGH), without a significant impact on overall growth velocity, but with favorable metabolic outcomes. Findings support multifactorial drivers of linear growth beyond the GH/IGF-1 pathway. Likely contributors include insulin signaling associated with adiposity, permissive thyroid hormone action, local growth-plate paracrine pathways, and, in hypogonadism, delayed epiphyseal closure. Genetic modifiers that enhance chondrogenesis or delay growth-plate fusion may contribute. We also reviewed the published literature on “growth without GH,” integrating single-case reports and series to contextualize these mechanisms and outcomes. In conclusion, profound GH deficiency does not preclude near-normal or accelerated growth. In “growth without GH,” therapeutic priorities should pivot from stature to cardiometabolic risk reduction. rhGH may be considered to improve metabolism when individualized and closely monitored, recognizing that height velocity is often adequate. Notably, rhGH consistently improved lipid profiles and steatohepatitis in two patients, suggesting a primarily metabolic benefit. Lifelong follow-up from childhood into adulthood is essential. Full article

Background: Sarcopenia and sarcopenic obesity are increasingly recognized in kidney transplant recipients (KTRs), yet their molecular underpinnings remain poorly defined. We sought to synthesize current evidence on biomarker associations with muscle loss and function in the post renal transplant setting. Methods: A comprehensive search of PubMed/MEDLINE and Cochrane databases was conducted according to PRISMA guidelines. Studies evaluating biomarkers related to sarcopenia or sarcopenic obesity in adult and pediatric KTRs were included. Quality assessment was performed with the NHLBI tool. Results: Seven studies were included, encompassing 548 KTRs. Myostatin levels predicted sarcopenia in KTRs (cut-off: 390 pg/mL) and inversely correlated with Metabolic equivalent of Tasks (METs), handgrip strength (HGS), and graft performance. Although adiponectin was negatively correlated with body fat, its high-molecular-weight isoform was linked to lower muscle mass and long-term graft decline. Leptin was associated with sarcopenic obesity and lower estimated Glomerular Filtration Rate (eGFR). Insulin like Growth Factor-1 (IGF-1) independently predicted HGS but not muscle mass. Brain-derived neurotrophic factor (BDNF) levels predicted sarcopenia (cut off: 17.8 ng/mL) and reflected physical activity levels. Visfatin showed no association with sarcopenia but it was positively correlated with eGFR. Lastly, certain polymorphisms of Alpha-actinin-3 (ACTN3) were shown to genetically predispose to post-transplant sarcopenia. Conclusions: These emerging candidate biomarkers provide promising mechanistic insight into post-transplant muscle decline and may ultimately support more personalized risk assessment. Further validation is needed, and functional measures remain the most reliable clinical tools at present. Full article

Chronic hyperglycemia inflicts serious cellular damage by inducing oxidative stress through the excessive production of free radicals. This oxidative milieu may impair the cellular redox capacity and disrupt the insulin-like growth factor (IGF) system, thereby increasing the risk of cardiovascular complications. This study aimed to investigate plasma levels of components of the IGF system and antioxidant biomarkers in young adults with type 1 diabetes mellitus (T1DM) compared to age-matched healthy controls in Brazil. This study included 129 patients with T1DM (76 female, 53 male; mean age 26.97 ± 0.6 years) and 95 healthy controls (61 female, 34 male; mean age 27.35 ± 0.68 years). Young Brazilian adults with T1DM had significantly lower mean IGF-I and higher mean IGFBP-1 levels compared to healthy controls. The T1DM group showed a more atherogenic profile, characterized by a significantly elevated ApoB/ApoA1 ratio and increased oxidized LDL levels. However, a subset of patients with significantly better glycemic control exhibited serum IGF-I and IGFBP-1 levels within the normal range observed in controls, which may indicate the presence of residual functional beta-cell activity or reflect better glycemic control in this subgroup. Antioxidant components and oxidative stress biomarkers were significantly upregulated in the T1DM group compared to the control group, suggesting a compensatory adaptive response. No significant correlation was observed between biomarkers of oxidative stress and the IGF-system. Full article

Musculoskeletal injuries involving volumetric muscle loss remain difficult to treat due to limited regenerative capacity and the lack of physiologically relevant experimental models. This study introduces a computer-controlled ex vivo mouse hindlimb culturing platform that applies dynamic mechanical loading to evaluate muscle regeneration in a critical-size tibialis anterior (TA) defect. The defect was treated with an injectable myoblast-laden nanofibrous scaffold composed of polycaprolactone nanofibers and collagen (PNCOL). The ex vivo mouse hindlimb culturing platform maintained tissue viability and transmitted physiological strain across bone and muscle without disrupting the unity of the bone–muscle structure. PNCOL treatment under mechanical loading enhanced muscle fiber organization, extracellular matrix regeneration, and anti-inflammatory responses (CD206) while upregulating paired box 7 (PAX7), myogenic factor 5 (MYF5), myogenic regulatory factor 4 (MRF4), and transforming growth factor beta1 (TGFβ1) expression. Cytokine profiling revealed an anabolic shift involving wingless/integrated (WNT) and insulin-like growth factor-1 (IGF-1) signaling, indicating a pro-regenerative microenvironment. Overall, the combination of mechanical stimulation and biomaterial-based therapy significantly improved muscle regeneration within a controlled ex vivo model. This multidimensional approach provides a reproducible and ethical platform that advances musculoskeletal regenerative research while reducing animal use. Full article

Background: Intracellular delivery of high-molecular-weight proteins is limited by the cell membrane. Cell-penetrating peptides (CPPs) offer a potential solution, but effective cytosolic delivery remains hindered by endosomal sequestration. Pas2r12, a CPP-derived peptide, facilitates cytosolic delivery of proteins including immunoglobulin G. Because Pas2r12 internalization occurs via caveolae-dependent endocytosis, we hypothesized that cell-surface receptors contribute to uptake. Methods: HEK293 cells were treated with Pas2r12 alone or complexed with enhanced green fluorescent protein (EGFP). Phosphorylation of insulin receptor (INSR), insulin-like growth factor 1 receptor (IGF1R), and extracellular signal–regulated kinase 1/2 (ERK1/2) was analyzed by Western blot. Linsitinib was used to inhibit INSR/IGF1R kinase activity. Cytosolic delivery was assessed by confocal microscopy, and receptor involvement was evaluated using siRNA-mediated knockdown and receptor overexpression. Results: Pas2r12 alone transiently increased INSR/IGF1R phosphorylation at 2 min (6.6-fold), which was suppressed by linsitinib (1.3-fold), and strongly increased ERK1/2 phosphorylation (6.2-fold), which was not inhibited by linsitinib. Pas2r12–EGFP did not induce detectable INSR/IGF1R phosphorylation in parental cells but increased ERK1/2 phosphorylation (3.4-fold). Linsitinib markedly reduced cytosolic EGFP delivery to 16% of control. INSR knockdown decreased delivery to 13–16%, and IGF1R knockdown to 19–65%. In INSR-overexpressing lines, Pas2r12–EGFP induced INSR/IGF1R phosphorylation (6.0-fold) and enhanced delivery (230–270%). In IGF1R-overexpressing lines, Pas2r12–EGFP did not induce phosphorylation, and delivery decreased to 60–69%. Conclusions: Pas2r12-mediated cytosolic delivery involves both INSR and IGF1R, with INSR contributing more prominently. These findings, including the largely INSR/IGF1R-independent ERK1/2 activation, provide mechanistic insight into Pas2r12-mediated protein delivery. Full article

Ovarian aging (OA) results from the senescence of different cell types present in the ovary, decreasing female fertility and quality of life and augmenting the risk of a variety of fertility-unrelated pathological conditions. The changes observed in the ovarian cells are accompanied by changes occurring in various elements of the hypothalamic–pituitary–ovarian (HPO) axis, the complex endocrine system that regulates the female reproductive cycle. Issues pertaining to the HPO axis have been addressed in animal models via hormonal treatments with preparations inhibiting ovarian follicular recruitment at the level of the receptors of gonadotropin-releasing hormone (GnRH)-secreting neurons, mainly acting on glutamate- and gamma-aminobutyric acid (GABA)-driven signaling. GnRH agonists and antagonists have also been used in women exposed to chemotherapeutics. HPO-independent OA can be delayed through the administration of different antioxidants and mitochondria-protecting agents, among which melatonin has been shown to be particularly useful. Other therapeutic approaches used with success in women include hormonal and growth factor (GF) modulators, such as growth hormone (GH), insulin-like growth factor 1 (IGF-1), vascular endothelial growth factors (VEGF), and dehydroepiandrosterone (DHEA), and the development of patient-tailored combination-based therapies (IGF-1 + VEGF + DHEA) has also been suggested. Intraovarian injection of autologous platelet-rich plasma (PRP), mitochondrial donation through pronuclear transfer, and ovarian tissue cryopreservation and autotransplantation have also yielded promising results in women, and their use can preserve not only fertility but also the ovarian endocrine function. Personalized mixtures of specific agents (desatinib, quercetin, rapamycin, metformin, resveratrol, melatonin, and coenzyme Q10) targeting different cell types in the ovary are currently under investigation. Overall, this review aims to present a global view of the subject, uniting the physiological and molecular background of this pathology with the history and development of potential treatment strategies and new perspectives in this domain. As such, this study may be helpful both to clinicians facing problems resulting from OA and to researchers pursuing further developments in this field. Full article

This investigation employed a between-participant design comparing acute and chronic changes in brain-derived neurotrophic factor (BDNF), cathepsin B (CatB), insulin-like growth factor-1 (IGF-1), and interleukin-6 (IL-6) across four resistance training (RT) protocols differing in proximity to failure, while also examining inter-biomarker correlations. Thirty-eight resistance-trained men completed an eight-week intervention, training three times per week, allocated to one of four groups based on repetitions-in-reserve (RIR): 4–6 RIR, 1–3 RIR, 0–3 RIR, and 0 RIR. Serum was collected immediately before and after training on day 1 of weeks 1 and 7. The analysis revealed the main effects of Session for BDNF and IL-6 (posterior probability > 99%), indicating exercise-induced elevation independent of proximity to failure. Additionally, CatB demonstrated a Session × Week interaction (posterior probability > 99%), indicating a difference in the acute response between week 7 and week 1. No compelling evidence emerged for IGF-1 effects, and inter-biomarker correlations were weak and inconsistent. Notably, this is the first investigation to demonstrate RT-induced transient CatB elevation. These findings suggest that exercise-induced neuroprotective biomarker responses may be achieved while training relatively far from failure, potentially avoiding the neuromuscular fatigue, injury risk, and recovery demands associated with failure training. Full article

Background: Obesity is a metabolic condition that may impair insulin sensitivity and disrupt glucose homeostasis. Since insulin and glucose affect insulin-like growth factor-1 (IGF-1), disruptions in this axis may elevate the risk of chronic diseases. Intermittent fasting (IF) modulates metabolic parameters, but the impacts on glucose regulation and IGF-1 remain underexplored. This study aimed to assess the short-term effects of two IF types, time-restricted feeding (TRF) and alternate-day modified fasting (ADMF), on fasting blood glucose (FBG) and IGF-1 in obese young women. Methods: A quasi-experimental pretest–posttest control group design was conducted over 20 days. The 31 subjects were allocated into ADMF (n = 10), TRF (n = 11), and Control (n = 10). After excluding dropouts and outliers, the final sample consisted of 22 subjects (ADMF = 7, TRF = 8, Control = 7). FBG and IGF-1 serum were measured pre- and post-intervention. Results: The FBG post-intervention significantly increased in TRF (p = 0.001) and ADMF (p = 0.036) groups, but not in Controls. Only the TRF group showed a significant reduction in IGF-1 levels (p < 0.001). Nevertheless, the ADMF group exhibited substantial decreases in body weight (p = 0.047) and visceral fat (p = 0.017). Conclusions: A 20-day IF in obese young women induced distinct metabolic effects: TRF lowered IGF-1, ADMF reduced adiposity, and both regimens increased FBG. These findings suggest that early changes in glucose regulation are highly dependent on the specific dietary regimen used. Specifically, TRF predominantly influences endocrine regulation (IGF-1 axis), while ADMF favours adiposity reduction. The concurrent rise in FBG may reflect a transient shift in glucose homeostasis during the early stages of fasting. Full article