K. Sreekumaran Nair, M.D., Ph.D.

The purpose of this study is to use neurological techniques to obtain quantitative measurements of nervous system control of skeletal muscle activity in adults aged 18-80 who are either long-term resistance exercisers or who are untrained.

This study is being done to determine how gender affirming hormone therapy alters muscle strength, body composition, metabolism, and muscle cell function.

The aim of the study is to investigate the effects of a 3-month resistance exercise program (in people aged 50 to 75) on muscle mass, body composition, muscle strength, brain function and cognition, muscle efficiency processing blood sugar, the body’s ability to build muscle, and fat cells.

Earlier research has shown that exercise has significant benefits in preventing certain diseases and conditions such as diabetes, dementia, heart disease, and more. We also know from other research that resistance exercise (lifting weights) and aerobic exercise (running, biking, walking), improve metabolism through separate ways on the molecular level, also called “molecular pathways.” With new and sophisticated technologies, we can analyze these molecular pathways to learn how exercise improves health. 

The purpose of the study is to understand why resistance exercise can prevent disease though analyzing the ‘molecular pathways’ in correlation with blood sugar to understand its effects on diabetes. We also will correlate these results with brain scan and cognitive tests to understand the mechanisms behind cognitive decline and dementia. 

Participants in this study will undergo a series of baseline measurements including but not limited to blood tests, brain scans, aerobic exercise tests, body composition scans, resistance exercise, a 24-hour research visit, 4 needle muscle biopsies, 2 needle fat biopsies, and an infusion of amino acids (the building blocks of muscles). 

Following the completion of the baseline visits, participants will be randomly placed into a resistance training group or a control group. 
1.    Resistance Training Group: Participants put into the resistance training program will take part in a personalized resistance training program and meet with a personal trainer four times a week for three months. Following the three months of resistance training participants will repeat the baseline visits and will be completed with the study. 
2.    Control Group: Participants put into the control group are asked not to make any lifestyle changes for 3 months. Following the 3 months, they will come back for a repeat of the baseline measurements. At this point they will have the choice to take part in the resistance training program, followed by a third set of baseline measurements. 

Remuneration is provided. 

Study title: Molecular Mechanisms of Exercise Benefits to Insulin Resistant People
IRB #: 19-006273
Principle Investigator: Dr. K Sreekumaran Nair
 

The purpose of this study is to determine the effects of transient insulin deprivation in people with type 1 DM (T1DM) and Total Pancreatomy on synthesis of specific plasma proteins applying stable isotope-proteome approach.

The purpose of this study is to seek and identify the mechanistic underpinnings of the effects of resistance exercise (RE) on insulin sensitivity.

The purpose of this study is to determine the content of exosomes in plasma released following one session of acute exercise. This study will apply novel methodologies developed in our laboratory to identify molecules such as proteins and miRNAs that may be therapeutically useful in treating type 2 diabetes, obesity, and age-related disorders. 

Muscle proteins accumulate damage during aging and leads to the loss of muscle mass and function in older people. Exercise can increase the making of new proteins and removal of older proteins, but it is not known if the effect changes with aging or type of exercise. The investigators will determine the ability for endurance, resistance, or a combination of exercise training to remove older-damaged proteins and make newer-functional muscle proteins in groups of younger and older people. The investigators will particularly study protein that are involved with energy production (mitochondrial proteins) and force production (contractile proteins).

Hypothesis 1: Older people will have greater accumulation of damaged proteins than younger people.

Hypothesis 2: Aerobic exercise will decrease the accumulation of damaged forms of contractile and mitochondrial proteins in younger and older people.

Hypothesis 3: Resistance exercise will decrease the accumulation of damaged forms of contractile proteins in younger and older people.

The investigators will determine whether people with high muscle mitochondrial capacity produce higher amount of reactive oxygen species (ROS) on consuming high fat /high glycemic diet and thus exhibit elevated cellular oxidative damage. The investigators previously found that Asian Indian immigrants have high mitochondrial capacity in spite of severe insulin resistance. Somalians are another new immigrant population with rapidly increasing prevalence of diabetes. Both of these groups traditionally consume low caloric density diets, and the investigators hypothesize that when these groups are exposed to high-calorie Western diets, they exhibit increased oxidative stress, oxidative damage, and insulin resistance. The investigators will compare Somalians and NE Americans who are matched for age, BMI, and sex. The investigators will measure ROS production in skeletal muscle following high fat/high glycemic diet vs. healthy diet. The investigators will compare the oxidative damage to proteins, DNA, and lipids in these two populations following 10 days of high fat/high glycemic index diet in comparison with low fat diet. The investigators will determine if elevated levels of oxidative damage in Somali immigrant populations is accompanied by high mitochondrial capacity, higher ROS-emitting potential, and lower insulin sensitivity than NE. The proposed study will be performed utilizing the state-of-the-art proteomic and metabolomic methods many of which were recently developed in our laboratory. The investigators expect the results from this study to provide seminal insights into the underlying mechanism of insulin resistance and type 2 diabetes, in addition to demonstrating mechanisms by which a functional proteome is maintained in vivo.

The purpose of this study is to establish an arterial/venous method to measure the activity of the Tricarboxylic Acid or cell metabolism cycle directly in the tissues of human beings. There will also be correlative studies on the proteome, metabolome, oxygen consumption, carbon dioxide production and exosomes related to TCA cycle activity.

The purpose of this study is to better understand the link between insulin resistance and dementia. Earlier studies have shown that people with insulin resistance are two to four times more likely to develop Alzheimer’s disease and other dementias. Other studies have shown a link between the drug Metformin (the most widely used medication to treat prediabetes and type 2 diabetes) and a reduction in the development of dementia.

The aim of this study is to investigate if 40 weeks of Metformin treatment (in people 60+ years) enhances brain function and how brain function interacts with the body’s metabolism in people with insulin resistance and in people without insulin resistance.

Insulin is a hormone produced by the pancreas that deals with sugar (glucose) in the blood. When we eat food, blood sugar levels increase, and the pancreas produces more insulin to keep blood sugar levels stable. If blood sugar decreases, then insulin levels decrease. If the body becomes resistant to insulin, then the body requires more insulin to balance out blood sugar levels. If this continues, eventually the pancreas is not able to produce the amount of insulin needed to balance out blood sugar leading to an elevated fasting blood sugar (fasting blood glucose value greater than 100 mg/dL). Insulin resistance is a primary risk factor for developing type 2 diabetes, heart disease, and dementia.

This study is recruiting two groups of people: people with insulin resistance and people without insulin resistance. To qualify for the insulin resistance group, a person would need to have an elevated fasting blood sugar test between 100mg/dL and 140mg/dL. To qualify for the non-insulin resistant group a person would need a blood sugar under 95mg/dL.

In people with insulin resistance the study will be measuring changes in brain functions, cognitive ability, and body’s metabolism. These series of tests are performed twice, once before and once after 40 weeks of taking Metformin. Brain functions are measured through a series of brain scans. Cognitive ability is measured using computerized tests. To measure the body’s metabolism, we measure insulin resistance during an overnight stay, blood tests to measure biomarkers, capacity for exercise, body composition scans, and muscle will be assessed from needle muscle biopsies.

In people without insulin resistance, the study will be collecting baseline measurements on brain function, cognitive ability, and body’s metabolism. These tests are performed once. Brain functions are measured through a series of brain scans. Cognitive ability is measured using computerized tests. To measure the body’s metabolism, we measure insulin resistance during an overnight stay, blood tests to measure biomarkers, and a body composition scan.

Remuneration and a travel reimbursement are provided.

This study is being done to understand metformin's mechanisms of action regarding glucose production, protein metabolism, and mitochondrial function.

What are the effects of transient insulin deprivation on brain structure, blood flow, mitochondrial function, and cognitive function in T1DM patients? What are the effects of transient insulin deprivation on circulating exosomes and metabolites in T1DM patients?