Effect of Age on Glucose and Lipid Metabolism
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|ClinicalTrials.gov Identifier: NCT01737164|
Recruitment Status : Completed
First Posted : November 29, 2012
Last Update Posted : February 19, 2016
|Condition or disease||Intervention/treatment||Phase|
|Glucose Metabolism Disorders Lipid Metabolism Disorders Metabolic Diseases||Behavioral: Aerobic Exercise||Not Applicable|
Aging is a major risk factor for the development of type 2 diabetes (T2DM). Approximately 50% of subjects aged ≥65 have diabetes or impaired glucose tolerance, a pre-diabetic state. Skeletal muscle is the main site of insulin-stimulated glucose disposal and aging is characterized by muscle insulin resistance. It has been suggested that the insulin resistance of aging results from an age-related accumulation of intramyocellular lipids which impair insulin action. However, the molecular basis for the accumulation of intramyocellular fat and insulin resistance in the elderly remains unknown. AMP-activated protein kinase (AMPK) is an energy-sensing enzyme whose activation results in increased fatty acid oxidation. Purpose: In the proposed study, we will test the hypotheses that the decrease in fat oxidation that occurs in muscle from older human subjects is secondary to an age-mediated reduction in AMPK signaling, in vivo, and that upregulating AMPK signaling through exercise training will result in (and correlate with) increased fat oxidation, reduced intramyocellular lipids, and improved insulin action. Using a primary human muscle cell culture system, also we will test that hypotheses that reduced AMPK signaling in old myotubes leads to lower fat oxidation (in vitro) and that chemical activation of AMPK in old myotubes to the same level as young muscle cells will restore insulin action and help prevent fat-induced insulin resistance. To test these hypotheses the following specific aims (objectives) are proposed:
Specific Aim 1) To determine whether reduced AMPK signaling in muscle from older subjects, in vivo, is associated with lower fat oxidation rates and insulin resistance, and whether physical activity improves glucose homeostasis in older subjects by upregulating AMPK signaling in muscle. We will test the hypotheses that (i) reductions in AMPK signaling in muscle from older subjects will be associated with (predict) lower fat oxidation rates and insulin resistance, in vivo; and (ii) training-induced increases in AMPK signaling in older subjects will be associated with (predict) increases in fat oxidation, reductions in intramyocellular lipids, and improvements in insulin action/sensitivity.
Specific Aim 2) To determine whether age-related declines in AMPK signaling are involved in the reductions in fat oxidation and insulin resistance that occur in aging. Using an in vitro primary muscle cell culture system, we will test the hypotheses that (i) reduced AMPK signaling in myotubes from older subjects leads to decreased mitochondrial fatty acid oxidation; and (ii) reduced AMPK signaling and fat oxidation in myotubes from older subjects will result in increased susceptibility to fat-induced insulin resistance.
Specific Aim 3) To examine whether the age-related reductions in fat oxidation and insulin sensitivity in old muscle cells can be reversed by upregulating AMPK signaling. We will test the hypothesis that chemical activation of AMPK in old myotubes (in vitro) to the same level as young muscle cells will restore insulin signaling and help prevent fat-induced insulin resistance.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||44 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||Effect of Age on Glucose and Lipid Metabolism|
|Study Start Date :||September 2010|
|Actual Primary Completion Date :||June 2015|
|Actual Study Completion Date :||December 2015|
Experimental: Aerobic Exercise - Older Subjects
Subjects aged 65 and higher will perform 16 weeks of moderate intensity exercise
Behavioral: Aerobic Exercise
Experimental: Aerobic Exercise - Young Subjects
Subjects 18-30 years old will perform 16 weeks of moderate intensity exercise
Behavioral: Aerobic Exercise
- Effect of Age on Glucose and Lipid Metabolism [ Time Frame: 16 weeks ]Effect of Age on Glucose and Lipid Metabolism; Measurement of glucose and lipid metabolism will be done pre and post exercise in two groups (younger and older subjects)
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01737164
|United States, Texas|
|Texas Diabetes Insitute|
|San Antonio, Texas, United States, 78207|
|Principal Investigator:||Nicolas Musi, MD||The University of Texas Health Science Center at San Antonio|