Dataset Information

Low circulating levels of IGF-1 in healthy adults are associated with reduced ?-cell function, increased intramyocellular lipid, and enhanced fat utilization during fasting.

ABSTRACT: Low serum IGF-1 levels have been linked to increased risk for development of type 2 diabetes. However, the physiological role of IGF-1 in glucose metabolism is not well characterized.Our objective was to explore glucose and lipid metabolism associated with variations in serum IGF-1 levels.IGF-1 levels were measured in healthy, nonobese male volunteers aged 18 to 50 years from a biobank (n = 275) to select 24 subjects (age 34.8 ± 8.9 years), 12 each in the lowest (low-IGF) and highest (high-IGF) quartiles of age-specific IGF-1 SD scores. Evaluations were undertaken after a 24-hour fast and included glucose and glycerol turnover rates using tracers, iv glucose tolerance test to estimate peripheral insulin sensitivity (IS) and acute insulin and C-peptide responses (indices of insulin secretion), magnetic resonance spectroscopy to measure intramyocellular lipids (IMCLs), calorimetry, and gene expression studies in a muscle biopsy.Acute insulin and C-peptide responses, IS, and glucose and glycerol rate of appearance (Ra) were evaluated.Fasting insulin and C-peptide levels and glucose Ra were reduced (all P < .05) in low-IGF compared with high-IGF subjects, indicating increased hepatic IS. Acute insulin and C-peptide responses were lower (both P < .05), but similar peripheral IS resulted in reduced insulin secretion adjusted for IS in low-IGF subjects (P = 0.044). Low-IGF subjects had higher overnight levels of free fatty acids (P = .028) and ?-hydroxybutyrate (P = .014), increased accumulation of IMCLs in tibialis anterior muscle (P = .008), and a tendency for elevated fat oxidation rates (P = .058); however, glycerol Ra values were similar. Gene expression of the fatty acid metabolism pathway (P = .0014) was upregulated, whereas the GLUT1 gene was downregulated (P = .005) in the skeletal muscle in low-IGF subjects.These data suggest that serum IGF-1 levels could be an important marker of ?-cell function and glucose as well as lipid metabolic responses during fasting.

SUBMITTER: Thankamony A

PROVIDER: S-EPMC4413372 | biostudies-literature | 2014 Jun

REPOSITORIES: biostudies-literature

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Low circulating levels of IGF-1 in healthy adults are associated with reduced β-cell function, increased intramyocellular lipid, and enhanced fat utilization during fasting.

Thankamony Ajay A Capalbo Donatella D Marcovecchio M Loredana ML Sleigh Alison A Jørgensen Sine Wanda SW Hill Nathan R NR Mooslehner Katrin K Yeo Giles S H GS Bluck Les L Juul Anders A Vaag Allan A Dunger David B DB

The Journal of clinical endocrinology and metabolism 20140311 6

<h4>Context</h4>Low serum IGF-1 levels have been linked to increased risk for development of type 2 diabetes. However, the physiological role of IGF-1 in glucose metabolism is not well characterized.<h4>Objective</h4>Our objective was to explore glucose and lipid metabolism associated with variations in serum IGF-1 levels.<h4>Design, setting and participants</h4>IGF-1 levels were measured in healthy, nonobese male volunteers aged 18 to 50 years from a biobank (n = 275) to select 24 subjects (age ...[more]

PMID: 24617714

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Project description:Fatty acids are stored within the muscle as intramyocellular lipids (IMCL). Some, but not all, studies indicate that following a high-fat diet (HFD), IMCL may accumulate and affect insulin sensitivity. This systematic review and meta-analysis aimed to quantify the effects of an HFD on IMCL. It also explored the potential modifying effects of HFD fat content and duration, IMCL measurement technique, physical activity status, and the associations of IMCL with insulin sensitivity. Five databases were systematically searched for studies that examined the effect of ≥3 d of HFD (>35% daily energy intake from fat) on IMCL content in healthy individuals. Meta-regressions were used to investigate associations of the HFD total fat content, duration, physical activity status, IMCL measurement technique, and insulin sensitivity with IMCL responses. Changes in IMCL content and insulin sensitivity (assessed by hyperinsulinemic-euglycemic clamp) are presented as standardized mean difference (SMD) using a random effects model with 95% confidence intervals (95% CIs). Nineteen studies were included in the systematic review and 16 in the meta-analysis. IMCL content increased following HFD (SMD = 0.63; 95% CI: 0.31, 0.94, P = 0.001). IMCL accumulation was not influenced by total fat content (P = 0.832) or duration (P = 0.844) of HFD, physical activity status (P = 0.192), or by the IMCL measurement technique (P > 0.05). Insulin sensitivity decreased following HFD (SMD = -0.34; 95% CI: -0.52, -0.16; P = 0.003), but this was not related to the increase in IMCL content following HFD (P = 0.233). Consumption of an HFD (>35% daily energy intake from fat) for ≥3 d significantly increases IMCL content in healthy individuals regardless of HFD total fat content and duration of physical activity status. All IMCL measurement techniques detected the increased IMCL content following HFD. The dissociation between changes in IMCL and insulin sensitivity suggests that other factors may drive HFD-induced impairments in insulin sensitivity in healthy individuals. This trial was registered at PROSPERO as CRD42021257984.

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Dataset Information

Low circulating levels of IGF-1 in healthy adults are associated with reduced ?-cell function, increased intramyocellular lipid, and enhanced fat utilization during fasting.

Publications

Low circulating levels of IGF-1 in healthy adults are associated with reduced β-cell function, increased intramyocellular lipid, and enhanced fat utilization during fasting.

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