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The aim of this study is to investigate whether metformin has inhibitory effect on exercise-induced lipolysis in subcutaneous adipose tissue in healthy lean man. Ten healthy lean mean will follow protocols consisting of 60 minutes of exercise on bicycle ergometer combined with a) orally administered metformin and b) locally administered metformin into adipose tissue and c) without metformin treatment. Microdialysis is used for assessment of metabolites in situ in subcutaneous adipose tissue.
Metformin and physical activity are often recommended as the first therapeutic agents to improve glycemic control for prediabetes and type 2 diabetes (ADA). It has been reported that metformin decrease plasma concentration of non-esterified fatty acids in patients with type 2 diabetes which might be associated with the inhibition of lipolysis in adipose tissue. However, the inhibition of lipolysis during physical exercise, would not be probably beneficial. Thus, the effect of metformin on lipolysis during exercise is investigated in this protocol. As the lipolysis regulation is often impaired in obese and diabetic patients, the healthy lean men were chosen for this pilot study. Glycerol will be analyzed as a measure of lipolytic rate in adipose tissue and in plasma. Lactate levels will be observed. Our findings should provide a new background about the combination of physical activity and metformin medication.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Metformin oral +exercise | Experimental | Metformin, one dose 2000mg, 2.5h before the start of 60 min physical exercise |
|
| Metformin local in AT +exercise | Active Comparator | Metformin perfused into microdialysis probe inserted in adipose tissue, 0.3ug/min 1.5h before the exercise and during 60min physical exercise |
|
| No metformin + exercise | Active Comparator | 60min physical exercise without pretreatment of metformin |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Metformin Oral | Drug |
|
| |
| Metformin local in AT |
| Measure | Description | Time Frame |
|---|---|---|
| Change in adipose tissue lipolysis in response to exercise | Glycerol concentration in dialysate outcoming from adipose tissue and in plasma - kinetic study | Minute -60, 15, 30, 45, 60 and 120 from the start of exercise |
| Measure | Description | Time Frame |
|---|---|---|
| Change in lactate production in response to exercise | Concentration of lactate in dialysate and in plasma - kinetic study | Minute -60, 15, 30, 45, 60 and 120 from the start of exercise |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Vladimir Stich, prof | Third faculty of medicine, Charles University in Prague | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Third Faculty of Medicine, Charles University | Prague | 100 00 | Czechia |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 20043143 | Background | Bourron O, Daval M, Hainault I, Hajduch E, Servant JM, Gautier JF, Ferre P, Foufelle F. Biguanides and thiazolidinediones inhibit stimulated lipolysis in human adipocytes through activation of AMP-activated protein kinase. Diabetologia. 2010 Apr;53(4):768-78. doi: 10.1007/s00125-009-1639-6. Epub 2009 Dec 31. | |
| 10656228 | Background |
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| ID | Term |
|---|---|
| D003924 | Diabetes Mellitus, Type 2 |
| D009043 | Motor Activity |
| ID | Term |
|---|---|
| D003920 | Diabetes Mellitus |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
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| ID | Term |
|---|---|
| D008687 | Metformin |
| D015444 | Exercise |
| ID | Term |
|---|---|
| D001645 | Biguanides |
| D006146 | Guanidines |
| D000578 | Amidines |
| D009930 | Organic Chemicals |
| D009043 |
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| Drug |
|
|
| Exercise | Other |
|
|
| Flechtner-Mors M, Ditschuneit HH, Jenkinson CP, Alt A, Adler G. Metformin inhibits catecholamine-stimulated lipolysis in obese, hyperinsulinemic, hypertensive subjects in subcutaneous adipose tissue: an in situ microdialysis study. Diabet Med. 1999 Dec;16(12):1000-6. doi: 10.1046/j.1464-5491.1999.00189.x. |
| 16901933 | Background | Ren T, He J, Jiang H, Zu L, Pu S, Guo X, Xu G. Metformin reduces lipolysis in primary rat adipocytes stimulated by tumor necrosis factor-alpha or isoproterenol. J Mol Endocrinol. 2006 Aug;37(1):175-83. doi: 10.1677/jme.1.02061. |
| D004700 | Endocrine System Diseases |
| D001519 | Behavior |
| Motor Activity |
| D009068 | Movement |
| D009142 | Musculoskeletal Physiological Phenomena |
| D055687 | Musculoskeletal and Neural Physiological Phenomena |