Combination of Metformin and Exercise in Management of Metabolic Abnormalities Observed in Type 2 Diabetes Mellitus

Filip Jevtovic Department of Kinesiology, College of Health and Human Performance, East Carolina University, Greenville, NC, USACorrespondence: Filip JevtovicEast Carolina University; School of Dental Medicine, Ledyard E. Ross Hall; 1851 MacGregor Downs Road, Mail Stop 701, Greenville, NC, 27834, US...

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Main Author: Jevtovic F
Format: Article
Language:English
Published: Dove Medical Press 2021-09-01
Series:Diabetes, Metabolic Syndrome and Obesity
Subjects:
Online Access:https://www.dovepress.com/combination-of-metformin-and-exercise-in-management-of-metabolic-abnor-peer-reviewed-fulltext-article-DMSO
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author Jevtovic F
author_facet Jevtovic F
author_sort Jevtovic F
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description Filip Jevtovic Department of Kinesiology, College of Health and Human Performance, East Carolina University, Greenville, NC, USACorrespondence: Filip JevtovicEast Carolina University; School of Dental Medicine, Ledyard E. Ross Hall; 1851 MacGregor Downs Road, Mail Stop 701, Greenville, NC, 27834, USATel +1 616 844 8323Fax +1 252 737 7024Email jevtovicf21@students.ecu.eduAbstract: Excess nutrient intake and lack of exercise characterize the problem of obesity and are common factors in insulin resistance (IR). With an increasing number of prediabetic, and type 2 diabetic populations, metformin is still the most prescribed glucose-lowering drug and is often accompanied by recommendations for regular physical exercise. Metformin, by the inhibition of complex 1 of the electron transport chain, and exercise, by increasing energy expenditure, both elicit a low cellular energy state that leads to improvements in glucose control via activation of adenosine 5ʹ monophosphate-activated protein kinase (AMPK). An augmented stimulation of the energy-sensing enzyme AMPK by either of the two modalities leads to an increase in glycogenolysis, glucose uptake, fat oxidation, a decrease in glycogen and protein synthesis, and gluconeogenesis in muscle and the liver, which are remarked as having positive effects on metabolic pathophysiology observed in IR and type 2 diabetes mellitus (T2DM). While both modalities exploit the energy-sensing enzyme AMPK to attain glucose homeostasis, the synergistic effect of these two treatments is not distinctly supported by the literature. Further, an antagonistic dynamic has been observed in cases where metformin and exercise were combined. Reduction of insulin-sensitizing effects of exercise and an overall hindrance of exercise performance and adaptations have been reported and could suggest the possible incongruity of these two modalities. The aim of this review is to elucidate the effect that metformin and exercise have on the management of the metabolic abnormalities observed in T2DM and to provide an insight into the interaction of these two modalities.Keywords: exercise, metformin, glucose control, type 2 diabetes mellitus, AMPK
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spelling doaj.art-de0e74bb84f0467e9bc61745ba7915332023-09-02T16:17:18ZengDove Medical PressDiabetes, Metabolic Syndrome and Obesity1178-70072021-09-01Volume 144043405768891Combination of Metformin and Exercise in Management of Metabolic Abnormalities Observed in Type 2 Diabetes MellitusJevtovic FFilip Jevtovic Department of Kinesiology, College of Health and Human Performance, East Carolina University, Greenville, NC, USACorrespondence: Filip JevtovicEast Carolina University; School of Dental Medicine, Ledyard E. Ross Hall; 1851 MacGregor Downs Road, Mail Stop 701, Greenville, NC, 27834, USATel +1 616 844 8323Fax +1 252 737 7024Email jevtovicf21@students.ecu.eduAbstract: Excess nutrient intake and lack of exercise characterize the problem of obesity and are common factors in insulin resistance (IR). With an increasing number of prediabetic, and type 2 diabetic populations, metformin is still the most prescribed glucose-lowering drug and is often accompanied by recommendations for regular physical exercise. Metformin, by the inhibition of complex 1 of the electron transport chain, and exercise, by increasing energy expenditure, both elicit a low cellular energy state that leads to improvements in glucose control via activation of adenosine 5ʹ monophosphate-activated protein kinase (AMPK). An augmented stimulation of the energy-sensing enzyme AMPK by either of the two modalities leads to an increase in glycogenolysis, glucose uptake, fat oxidation, a decrease in glycogen and protein synthesis, and gluconeogenesis in muscle and the liver, which are remarked as having positive effects on metabolic pathophysiology observed in IR and type 2 diabetes mellitus (T2DM). While both modalities exploit the energy-sensing enzyme AMPK to attain glucose homeostasis, the synergistic effect of these two treatments is not distinctly supported by the literature. Further, an antagonistic dynamic has been observed in cases where metformin and exercise were combined. Reduction of insulin-sensitizing effects of exercise and an overall hindrance of exercise performance and adaptations have been reported and could suggest the possible incongruity of these two modalities. The aim of this review is to elucidate the effect that metformin and exercise have on the management of the metabolic abnormalities observed in T2DM and to provide an insight into the interaction of these two modalities.Keywords: exercise, metformin, glucose control, type 2 diabetes mellitus, AMPKhttps://www.dovepress.com/combination-of-metformin-and-exercise-in-management-of-metabolic-abnor-peer-reviewed-fulltext-article-DMSOexercisemetforminglucose controltype 2 diabetes mellitusampk
spellingShingle Jevtovic F
Combination of Metformin and Exercise in Management of Metabolic Abnormalities Observed in Type 2 Diabetes Mellitus
Diabetes, Metabolic Syndrome and Obesity
exercise
metformin
glucose control
type 2 diabetes mellitus
ampk
title Combination of Metformin and Exercise in Management of Metabolic Abnormalities Observed in Type 2 Diabetes Mellitus
title_full Combination of Metformin and Exercise in Management of Metabolic Abnormalities Observed in Type 2 Diabetes Mellitus
title_fullStr Combination of Metformin and Exercise in Management of Metabolic Abnormalities Observed in Type 2 Diabetes Mellitus
title_full_unstemmed Combination of Metformin and Exercise in Management of Metabolic Abnormalities Observed in Type 2 Diabetes Mellitus
title_short Combination of Metformin and Exercise in Management of Metabolic Abnormalities Observed in Type 2 Diabetes Mellitus
title_sort combination of metformin and exercise in management of metabolic abnormalities observed in type 2 diabetes mellitus
topic exercise
metformin
glucose control
type 2 diabetes mellitus
ampk
url https://www.dovepress.com/combination-of-metformin-and-exercise-in-management-of-metabolic-abnor-peer-reviewed-fulltext-article-DMSO
work_keys_str_mv AT jevtovicf combinationofmetforminandexerciseinmanagementofmetabolicabnormalitiesobservedintype2diabetesmellitus