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The purpose of this research study is to learn more about how our body produces sugar, breaks down fat for fuel, and makes insulin (the major hormone that controls the production of blood sugar and fat breakdown) during a 24-hour day and how body fat and muscle are involved in these processes.
The purpose of this study is to determine whether there are diurnal differences in postprandial beta-cell function and hepatic insulin sensitivity and the factors that influence these metabolic functions, including insulin signaling, adipose tissue and systemic inflammation, nicotinamide phosphoribosyltransferase (NAMPT)-mediated nicotinamide adenine dinucleotide(NAD) biosynthesis, and sirtuin (silent mating type information regulation 2 homolog 1 (SIRT1)) in overweight human subjects.
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| Measure | Description | Time Frame |
|---|---|---|
| Determine postprandial beta-cell function (insulin secretion) after ingesting breakfast and dinner meals. | Postprandial pancreatic beta-cell function will be evaluated by using a mixed meal labelled with stable isotope tracers, in conjunction with stable isotope tracer infusion. Metabolic outcomes from the breakfast meal will be compared with values obtained after dinner. | 24 hours |
| Determine postprandial hepatic insulin sensitivity (suppression of endogenous glucose production) after ingesting breakfast and dinner meals. | Postprandial pancreatic hepatic insulin sensitivity will be evaluated by using a mixed meal labelled with stable isotope tracers, in conjunction with stable isotope tracer infusion. Metabolic outcomes from the breakfast meal will be compared with values obtained after dinner. | 24 hours |
| Measure | Description | Time Frame |
|---|---|---|
| Determine whether there is diurnal variability in muscle insulin signaling | This muscle samples will be obtained two times (every 12 hours for 24 hours)to assess NAMPT and NAD+ concentrations, SIRT1 activity, and factors involved in insulin signaling. | 24 hours |
| Determine whether there is diurnal variability in adipose tissue and systemic inflammation. |
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Inclusion Criteria:
Exclusion Criteria:
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The study population will consist of female subjects of all races and ethnic groups. Participants will be recruited by reviewing our database of research subjects containing thousands of research study volunteers and by St. Louis metro area postings.
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| Name | Affiliation | Role |
|---|---|---|
| Samuel Klein, M.D. | Washington University School of Medicine | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Washington University School of Medicine | St Louis | Missouri | 63110 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 29294006 | Derived | Yamaguchi S, Moseley AC, Almeda-Valdes P, Stromsdorfer KL, Franczyk MP, Okunade AL, Patterson BW, Klein S, Yoshino J. Diurnal Variation in PDK4 Expression Is Associated With Plasma Free Fatty Acid Availability in People. J Clin Endocrinol Metab. 2018 Mar 1;103(3):1068-1076. doi: 10.1210/jc.2017-02230. |
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| ID | Term |
|---|---|
| D050177 | Overweight |
| ID | Term |
|---|---|
| D044343 | Overnutrition |
| D009748 | Nutrition Disorders |
| D009750 | Nutritional and Metabolic Diseases |
| D001835 | Body Weight |
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Blood samples, adipose tissue samples and muscle samples
Subcutaneous adipose tissue samples will be obtained four times (every 6 hours for 24 hours) to evaluate NAMPT and NAD+ concentrations, SIRT1 activity, and markers of inflammation. |
| 24 hours |
| Determine whether there is diurnal variability in NAMPT-mediated NAD+ biosynthesis and SIRT1. | Blood samples will be obtained at regular intervals for 24 hours to evaluate; 1)plasma free fatty acids (FFA), glucose and insulin concentrations, 2)NAMPT and NAD+ concentrations, 3)SIRT1 activity,and 4)systemic markers of inflammation (C-reactive protein and interleukin (IL) -6). | 24 hours |
| D012816 |
| Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |