Summary of Study ST000485

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	ST000485
Study Title	D2 Glucose Quantifcation of obese patients on a 16 week caloric restriction from plasma
Study Type	timecourse
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 Metabolomics Core
Last Name	Nair
First Name	Sreekumaran
Address	200 First Street SW, Rochester, MN 55905
Email	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)	d
Analysis Type Detail	GC-MS
Release Date	2017-11-20
Release Version	1

Select appropriate tab below to view additional metadata details:

Project:

Project ID:	PR000367
Project DOI:	doi: 10.21228/M8MC7X
Project Title:	Mechanism by Which Caloric Restriction Improves Insulin Sensitivity in Sedentary Obese Adults
Project Type:	skeletal muscle ceramide, diacylglycerol, or amino acid metabolite levels
Project Summary:	effect of caloric restriction on insulin sensitivity through skeletal muscle ceramide, diacylglycerol, or amino acid metabolite levels
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
Email:	Nair.K@mayo.edu
Phone:	507-285-2415

Subject:

Subject ID:	SU000506
Subject Type:	Human
Subject Species:	Homo sapiens
Taxonomy ID:	9606
Species Group:	Human

Factors:

Subject type: Human; Subject species: Homo sapiens (Factor headings shown in green)

mb_sample_id	local_sample_id	visit	time (mins)	Category
SA024662	MS5023_4_-10	1	-10	Caloric Restriction
SA024663	MS5035_4_-10	1	-10	Caloric Restriction
SA024664	MS5027_4_-10	1	-10	Caloric Restriction
SA024665	MS5017_4_-10	1	-10	Caloric Restriction
SA024666	MS5009_4_-10	1	-10	Caloric Restriction
SA024667	MS5007_4_-10	1	-10	Caloric Restriction
SA024668	MS5011_4_-10	1	-10	Caloric Restriction
SA024669	MS5005_4_-10	1	-10	Caloric Restriction
SA024670	MS5037_4_-10	1	-10	Caloric Restriction
SA024671	MS5013_4_-10	1	-10	Caloric Restriction
SA024672	MS5015_4_-10	1	-10	Caloric Restriction
SA024673	MS5019_4_-10	1	-10	Control
SA024674	MS5031_4_-10	1	-10	Control
SA024675	MS5021_4_-10	1	-10	Control
SA024676	MS5043_4_-10	1	-10	Control
SA024677	MS5029_4_-10	1	-10	Control
SA024678	MS5033_4_-10	1	-10	Control
SA024679	MS5041_4_-10	1	-10	Control
SA024680	MS5025_4_-10	1	-10	Control
SA024681	MS5039_4_-10	1	-10	Control
SA024742	MS5023_6_120	1	120	Caloric Restriction
SA024743	MS5035_6_120	1	120	Caloric Restriction
SA024744	MS5005_6_120	1	120	Caloric Restriction
SA024745	MS5017_6_120	1	120	Caloric Restriction
SA024746	MS5011_6_120	1	120	Caloric Restriction
SA024747	MS5027_6_120	1	120	Caloric Restriction
SA024748	MS5013_6_120	1	120	Caloric Restriction
SA024749	MS5015_6_120	1	120	Caloric Restriction
SA024750	MS5009_6_120	1	120	Caloric Restriction
SA024751	MS5037_6_120	1	120	Caloric Restriction
SA024752	MS5007_6_120	1	120	Caloric Restriction
SA024753	MS5031_6_120	1	120	Control
SA024754	MS5039_6_120	1	120	Control
SA024755	MS5041_6_120	1	120	Control
SA024756	MS5033_6_120	1	120	Control
SA024757	MS5019_6_120	1	120	Control
SA024758	MS5025_6_120	1	120	Control
SA024759	MS5021_6_120	1	120	Control
SA024760	MS5043_6_120	1	120	Control
SA024761	MS5029_6_120	1	120	Control
SA024762	MS5037_7_140	1	140	Caloric Restriction
SA024763	MS5027_7_140	1	140	Caloric Restriction
SA024764	MS5035_7_140	1	140	Caloric Restriction
SA024765	MS5005_7_140	1	140	Caloric Restriction
SA024766	MS5013_7_140	1	140	Caloric Restriction
SA024767	MS5017_7_140	1	140	Caloric Restriction
SA024768	MS5011_7_140	1	140	Caloric Restriction
SA024769	MS5007_7_140	1	140	Caloric Restriction
SA024770	MS5009_7_140	1	140	Caloric Restriction
SA024771	MS5015_7_140	1	140	Caloric Restriction
SA024772	MS5023_7_140	1	140	Caloric Restriction
SA024773	MS5029_7_140	1	140	Control
SA024774	MS5043_7_140	1	140	Control
SA024775	MS5019_7_140	1	140	Control
SA024776	MS5031_7_140	1	140	Control
SA024777	MS5021_7_140	1	140	Control
SA024778	MS5039_7_140	1	140	Control
SA024779	MS5025_7_140	1	140	Control
SA024780	MS5033_7_140	1	140	Control
SA024781	MS5041_7_140	1	140	Control
SA024782	MS5023_8_160	1	160	Caloric Restriction
SA024783	MS5007_8_160	1	160	Caloric Restriction
SA024784	MS5015_8_160	1	160	Caloric Restriction
SA024785	MS5009_8_160	1	160	Caloric Restriction
SA024786	MS5027_8_160	1	160	Caloric Restriction
SA024787	MS5017_8_160	1	160	Caloric Restriction
SA024788	MS5013_8_160	1	160	Caloric Restriction
SA024789	MS5037_8_160	1	160	Caloric Restriction
SA024790	MS5011_8_160	1	160	Caloric Restriction
SA024791	MS5005_8_160	1	160	Caloric Restriction
SA024792	MS5035_8_160	1	160	Caloric Restriction
SA024793	MS5041_8_160	1	160	Control
SA024794	MS5025_8_160	1	160	Control
SA024795	MS5033_8_160	1	160	Control
SA024796	MS5039_8_160	1	160	Control
SA024797	MS5019_8_160	1	160	Control
SA024798	MS5029_8_160	1	160	Control
SA024799	MS5031_8_160	1	160	Control
SA024800	MS5043_8_160	1	160	Control
SA024801	MS5021_8_160	1	160	Control
SA024802	MS5023_9_180	1	180	Caloric Restriction
SA024803	MS5027_9_180	1	180	Caloric Restriction
SA024804	MS5007_9_180	1	180	Caloric Restriction
SA024805	MS5017_9_180	1	180	Caloric Restriction
SA024806	MS5035_9_180	1	180	Caloric Restriction
SA024807	MS5037_9_180	1	180	Caloric Restriction
SA024808	MS5013_9_180	1	180	Caloric Restriction
SA024809	MS5005_9_180	1	180	Caloric Restriction
SA024810	MS5015_9_180	1	180	Caloric Restriction
SA024811	MS5011_9_180	1	180	Caloric Restriction
SA024812	MS5009_9_180	1	180	Caloric Restriction
SA024813	MS5039_9_180	1	180	Control
SA024814	MS5029_9_180	1	180	Control
SA024815	MS5031_9_180	1	180	Control
SA024816	MS5019_9_180	1	180	Control
SA024817	MS5043_9_180	1	180	Control
SA024818	MS5021_9_180	1	180	Control
SA024819	MS5025_9_180	1	180	Control
SA024820	MS5033_9_180	1	180	Control
SA024821	MS5041_9_180	1	180	Control

Showing page 1 of 6 Results: 1 2 3 4 5 Next Last Showing results 1 to 100 of 560

Collection:

Collection ID:	CO000500
Collection Summary:	Blood samples were collected in a heated hotbox (131°F) through a retrograde intravenous catheter at baseline for glucose and hormone levels, and every 10 min during the clamp to maintain euglycemia. In addition, blood samples were collected every 20 min from 0600 to 0700, 0900 to 1000, and 1200 to 1300 to measure plasma [6,62H2]glucose. At 1330 h, a percutaneous needle muscle biopsy specimen (350–400 mg) was obtained from the vastus lateralis muscle under local anesthesia, immediately frozen in liquid nitrogen, and stored at −80°F for future analysis (27). This biopsy sample was used for analysis of TXNIP mRNA and protein content. The participant remained in the CRU through the remainder of the day and was given a weight-maintenance diet until 2200 h. At 0700 h the following morning, a second muscle biopsy specimen was obtained under local anesthesia, and ∼100 mg was used immediately for mitochondrial function measurements of isolated mitochondria and mtH2O2 emissions (28). The remainder was immediately frozen in liquid nitrogen and stored at −80°F for future analysis, including DAG, ceramide, and amino acid measurements (Fig. 1).
Sample Type:	Blood

Treatment:

Treatment ID:	TR000520
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.

Treatment ID:

TR000520

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.

Sample Preparation:

Sampleprep ID:	SP000513
Sampleprep Summary:	Glucose concentration was measured every 10 min during the insulin clamp with an Analox glucose analyzer (Analox Instruments, London, U.K.). [6,6-2H2]-d-glucose enrichment in the plasma and infusate was measured using gas chromatography–mass spectrometry. As described previously, the steady-state equations of Steele et al. (29) were used to calculate the rate of glucose appearance (Ra) and disappearance (Rd). EGP was calculated as the difference between total glucose Ra and the exogenous glucose infusion rate, peripheral insulin sensitivity was assessed from the rate of glucose infusion required to maintain euglycemia during the high-dose insulin clamp, and hepatic insulin sensitivity was assessed by the extent to which EGP was suppressed from baseline to low-dose hyperinsulinemia (26).

Sampleprep ID:

SP000513

Sampleprep Summary:

Glucose concentration was measured every 10 min during the insulin clamp with an Analox glucose analyzer (Analox Instruments, London, U.K.). [6,6-2H2]-d-glucose enrichment in the plasma and infusate was measured using gas chromatography–mass spectrometry. As described previously, the steady-state equations of Steele et al. (29) were used to calculate the rate of glucose appearance (Ra) and disappearance (Rd). EGP was calculated as the difference between total glucose Ra and the exogenous glucose infusion rate, peripheral insulin sensitivity was assessed from the rate of glucose infusion required to maintain euglycemia during the high-dose insulin clamp, and hepatic insulin sensitivity was assessed by the extent to which EGP was suppressed from baseline to low-dose hyperinsulinemia (26).

Combined analysis:

Analysis ID	AN000751
Analysis type	MS
Chromatography type	GC
Chromatography system	Agilent
Column	Agilent DB5-MS (30m × 0.25mm, 0.25um)
MS Type	EI
MS instrument type	Single quadrupole
MS instrument name	Agilent 5973
Ion Mode	POSITIVE
Units	mole percent enrichment

Chromatography:

Chromatography ID:	CH000539
Chromatography Summary:	Glucose concentration was measured every 10 min during the insulin clamp with an Analox glucose analyzer (Analox Instruments, London, U.K.). [6,6-2H2]-d-glucose enrichment in the plasma and infusate was measured using gas chromatography–mass spectrometry. As described previously, the steady-state equations of Steele et al. (29) were used to calculate the rate of glucose appearance (Ra) and disappearance (Rd). EGP was calculated as the difference between total glucose Ra and the exogenous glucose infusion rate, peripheral insulin sensitivity was assessed from the rate of glucose infusion required to maintain euglycemia during the high-dose insulin clamp, and hepatic insulin sensitivity was assessed by the extent to which EGP was suppressed from baseline to low-dose hyperinsulinemia (26).
Instrument Name:	Agilent
Column Name:	Agilent DB5-MS (30m × 0.25mm, 0.25um)
Chromatography Type:	GC

MS:

MS ID:	MS000665
Analysis ID:	AN000751
Instrument Name:	Agilent 5973
Instrument Type:	Single quadrupole
MS Type:	EI
Ion Mode:	POSITIVE