Mitochondrial Dysfunction in Diabetes (PGC-1)
PGC-1 and Mitochondrial Dysfunction in Diabetes, Aims 4 & 5
Visão geral do estudo
Status
Intervenção / Tratamento
Descrição detalhada
The investigators' prior research has focused on defining the changes in expression of nuclear encoded mitochondrial genes that predict changes in insulin sensitivity in skeletal muscle, with the goal of defining the molecular mechanisms underlying the connection between mitochondrial dysfunction and insulin resistance in skeletal muscle.
Three groups of subjects will be studied: lean, healthy control subjects (n=12) obese non-diabetic subjects (n=12) and patients with type 2 Diabetes Mellitus (n=12) for a total of 36 subjects. Twenty subjects have completed the study at Arizona State University; the remaining 16 subjects will be accrued at the Mayo Clinic in Arizona.
Subjects will come to the Mayo Clinic 4 times. On Study Day 1 Subjects will be screened with a medical history & physical and a 75 g oral glucose tolerance test to determine if they are eligible for the study. On Study Day 2, subjects will report to the clinic after an overnight fast, undergo a euglycemic clamp (using deuterated glucose) to determine insulin sensitivity, and in addition have a muscle biopsy (basal biopsy for comparison). On Study Day 3, subjects will report to the clinic after an overnight fast, and undergo a Volume Oxygen Maximum (VO_2 max) determination. On Study Day 4, subjects will report to the clinic after an overnight fast to perform an exercise bout with muscle biopsy 30 minutes after the end of exercise. This will be followed by an overnight fast, and an additional muscle biopsy at 24 hours post exercise.
Tipo de estudo
Inscrição (Real)
Estágio
- Não aplicável
Contactos e Locais
Locais de estudo
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Arizona
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Scottsdale, Arizona, Estados Unidos, 85259
- Mayo Clinic in Arizona
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Critérios de participação
Critérios de elegibilidade
Idades elegíveis para estudo
Aceita Voluntários Saudáveis
Gêneros Elegíveis para o Estudo
Descrição
Inclusion Criteria
- Subjects must be able to communicate meaningfully with the investigator and must be legally competent to provide written informed consent.
- Subjects may be of either sex with age as described in each protocol. Female subjects must be non-lactating and will be eligible only if they have a negative pregnancy test throughout the study period.
- Subjects must range in age as described in each specific protocol.
Subjects must have the following laboratory values:
- Hematocrit ≥ 35 vol%
- Serum creatinine ≤ 1.6 mg/dl
- Aspartate Aminotransferase (AST) (SGOT) < 2 times upper limit of normal
- Alanine Aminotransferase (ALT) (SGPT) < 2 times upper limit of normal
- Alkaline phosphatase < 2 times upper limit of normal
- Triglycerides < 150 mg/dl.
- Prothrombin Time (PT) 11.7 -14.3 seconds (during Intralipid/heparin infusion,PT will be determined to insure that it is < 1.5-2.0 times the normal value.)
- Partial thromboplastin time (PTT) 23.0-37.0 seconds.
Exclusion Criteria
- Subjects must not be receiving any of the following medications: thiazide or furosemide diuretics, beta-blockers, or other chronic medications with known adverse effects on glucose tolerance levels unless the patient has been on a stable dose of such agents for the past three months before entry into the study. Subjects may be taking a stable dose of estrogens or other hormonal replacement therapy, if the subject has been on these agents for the prior three months. Subjects taking systemic glucocorticoids are excluded.
- Subjects with a history of clinically significant heart disease (New York Heart Classification greater than grade II; more than non-specific ST-T wave changes on the EKG), peripheral vascular disease (history of claudication), or pulmonary disease (dyspnea on exertion of one flight or less; abnormal breath sounds on auscultation) will not be studied.
- Recent systemic or pulmonary embolus, untreated high-risk proliferative retinopathy, recent retinal hemorrhage, uncontrolled hypertension, systolic BP>180, diastolic BP>105, autonomic neuropathy, resting heart rate >100, electrolyte abnormalities.
Plano de estudo
Como o estudo é projetado?
Detalhes do projeto
- Finalidade Principal: Ciência básica
- Alocação: Não randomizado
- Modelo Intervencional: Atribuição Paralela
- Mascaramento: Nenhum (rótulo aberto)
Armas e Intervenções
Grupo de Participantes / Braço |
Intervenção / Tratamento |
|---|---|
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Experimental: Obese Non-Diabetic Subjects
All subjects on this arm will undergo exercise and muscle biopsies.
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Subjects will undergo a euglycemic clamp, VO_2 max determination, exercise periods and muscle biopsies.
|
|
Experimental: Type 2 Diabetic Subjects
All subjects on this arm will undergo exercise and muscle biopsies.
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Subjects will undergo a euglycemic clamp, VO_2 max determination, exercise periods and muscle biopsies.
|
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Experimental: Healthy Control Subjects
All subjects on this arm will undergo exercise and muscle biopsies.
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Subjects will undergo a euglycemic clamp, VO_2 max determination, exercise periods and muscle biopsies.
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O que o estudo está medindo?
Medidas de resultados primários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
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Protein Concentration of Mitochondria
Prazo: Study Day 4 (30 min after exercise) and (24 hours after exercise)
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Protein concentration will be determined from muscle biopsies by the method of Lowry.
75 micrograms of muscle lysate proteins will be separated on a 10% Sodium Dodecyl Sulfate Polyacrylamide Gel, and then visualized with Coomassie stain.
The gel lane will be cut into cubes, digested with trypsin and cleaned, then protein abundance will be determined using spectral counting.
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Study Day 4 (30 min after exercise) and (24 hours after exercise)
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Colaboradores e Investigadores
Patrocinador
Investigadores
- Investigador principal: Lawrence Mandarino, Ph.D., Mayo Clinic
Publicações e links úteis
Links úteis
Datas de registro do estudo
Datas Principais do Estudo
Início do estudo
Conclusão Primária (Real)
Conclusão do estudo (Real)
Datas de inscrição no estudo
Enviado pela primeira vez
Enviado pela primeira vez que atendeu aos critérios de CQ
Primeira postagem (Estimativa)
Atualizações de registro de estudo
Última Atualização Postada (Estimativa)
Última atualização enviada que atendeu aos critérios de controle de qualidade
Última verificação
Mais Informações
Termos relacionados a este estudo
Palavras-chave
Termos MeSH relevantes adicionais
Outros números de identificação do estudo
- 11-006065 Aim 4
- R01DK066483 (Concessão/Contrato do NIH dos EUA)
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