Summary of Study ST000483
This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR000367. The data can be accessed directly via it's Project DOI: 10.21228/M8MC7X This work is supported by NIH grant, U2C- DK119886.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
Study ID | ST000483 |
Study Title | Amino Acid Quantifcation of obese patients on a 16 week caloric restriction from Plasma |
Study Type | timecourse, quantitative measurements of amino acid |
Study Summary | Caloric restriction (CR) improves insulin sensitivity and reduces the incidence of diabetes in obese individuals. The underlying mechanisms whereby CR improves insulin sensitivity are not clear. We evaluated the effect of 16 weeks of CR on whole-body insulin sensitivity by pancreatic clamp before and after CR in 11 obese participants (BMI = 35 kg/m2) compared with 9 matched control subjects (BMI = 34 kg/m2). Compared with the control subjects, CR increased the glucose infusion rate needed to maintain euglycemia during hyperinsulinemia, indicating enhancement of peripheral insulin sensitivity. This improvement in insulin sensitivity was not accompanied by changes in skeletal muscle mitochondrial oxidative capacity or oxidant emissions, nor were there changes in skeletal muscle ceramide, diacylglycerol, or amino acid metabolite levels. However, CR lowered insulin-stimulated thioredoxin-interacting protein (TXNIP) levels and enhanced nonoxidative glucose disposal. These results support a role for TXNIP in mediating the improvement in peripheral insulin sensitivity after CR. |
Institute | Mayo Clinic |
Department | Endocrinology |
Laboratory | Mayo Clinic Metabolomics Resource Core |
Last Name | Nair |
First Name | Sreekumaran |
Address | 200 First Street SW, Rochester, MN 55905 |
Nair.K@mayo.edu | |
Phone | 507-285-2415 |
Submit Date | 2016-09-23 |
Publications | Mechanism by Which Caloric Restriction Improves Insulin Sensitivity in Sedentary Obese Adults. DOI: 10.2337/db15-0675 |
Raw Data File Type(s) | raw(Thermo) |
Analysis Type Detail | LC-MS |
Release Date | 2016-12-22 |
Release Version | 1 |
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Treatment:
Treatment ID: | TR000518 |
Treatment Summary: | Before and after 16 weeks of CR or CON, two outpatient visits and one inpatient visit were scheduled. Before the outpatient visits, participants were instructed to fast overnight from 10:00 p.m. the evening before and to avoid strenuous exercise for 24 h preceding the visits. One outpatient visit consisted of an MRI to measure subcutaneous and visceral fat distribution and magnetic resonance spectroscopy to measure skeletal muscle oxidative capacity (25). The second outpatient visit was for measurements of resting energy expenditure (REE) for the calculation of a weight-maintenance diet (Parvo Medics TrueOne 2400 Canopy system), DEXA scan (Lunar DPX-L; Lunar Radiation, Madison, WI), and VO2peak test on a bicycle ergometer (Fig. 1). Participants were admitted to the Clinical Research Unit (CRU) on the evening of the fifth day of the weight-maintaining diet provided by the CRU metabolic kitchen (Supplementary Fig. 1). The weight-maintenance meals (diet composition: 20% protein, 30% fat, 50% carbohydrate) were monitored daily to ensure that the correct calorie level was achieved. Upon admission to the CRU, no calories were consumed after 2100 h to achieve a 10-h fast before the two-stage insulin euglycemic pancreatic clamp the following morning, as previously published (26), with modifications as follows: the following morning at 0400 h, a primed [6,62H2]glucose bolus (6 mg ⋅ kg fat-free mass[FFM]−1) was administered, followed by a 9-h continuous infusion of [6,62H2]glucose (started at 4 mg ⋅ kgFFM−1 ⋅ h−1 then titrated downward over the infusion time period to match anticipated changes in endogenous glucose production [EGP]). At 0600 h, gas exchange was measured by indirect calorimetry for 30 min for REE determination. Then at 0700 h, glucagon (0.001 μg ⋅ kgFFM−1 ⋅ min−1), somatostatin (0.093 μg ⋅ kgFFM−1 ⋅ min−1), and growth hormone (0.0047 μg ⋅ kgFFM−1 ⋅ min−1) were infused for 6 h. Insulin was infused from 0700 to 1000 h at 0.62 mU ⋅ kgFFM−1 ⋅ min−1 and then from 1000 to 1300 h at 2.3 mU ⋅ kgFFM−1 ⋅ min−1. A 40% dextrose with 2% enrichment of [6,62H2]glucose was infused as needed to maintain blood glucose above 4.7 mmol/L from 0700 to 1000 h and then between 4.7 and 5.3 mmol/L from 1000 to 1300 h. |