A Possible Mechanism of Metformin in Improving Insulin Resistance in Diabetic Rat Models

Li, Mengsiyu; Hu, Xiaowen; Xu, Yeqiu; Hu, Xiaolin; Zhang, Chunxue; Pang, Shuguang

doi:10.1155/2019/3248527

Cited by 15 publications

(13 citation statements)

References 29 publications

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“…Diabetes is accompanied with dehydration, hyperglycemia, insulin deficiency or resistance, increased glycogenolysis, lipolysis, gluconeogenesis and these biochemical activities result in muscles wasting and loss of tissue protein (Ewenighiet al, 2015). Virdiet al, (2003) explained thatdiabetics suffer from dehydration and catabolism of fats and proteinsdue to unavailability of carbohydrates for utilization as an energy source.Since metformin increases insulin sensitivity (Li et al, 2019), it increased body weight of diabetic rats in the present study. However, because of itslowering effect on food and caloric intake as confirmed byLeeand Morley, (1998),its weight gain effect was the lowest compared with this induced by herbal treatments.SFP and SLP were found to decrease insulin resistance and have hypoglycemic effect.…”

Section: Discussionsupporting

confidence: 50%

Co-therapeutic effects of metformin and Sidr fruits and leaves in experimental diabetic rats

El-Hashash

2020

Egyptian Journal of Nutrition and Health

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Many diabetic patients prefer to use herbal medicine and treated with conventional drugs, concurrently. The main objective of this study was to evaluate the co-therapeutic effects of Sidr(Zizyphusspina-christi L.) fruits or leaves and metformin in diabetic rats. Forty two adult male albino rats were used and divided into seven groups (G1-G7). G1 was kept on basal diet (negative control), while other groups were subcutaneously injected with alloxan (120 mg/kg body weight).G2 was kept untreated as a positive control, while the other alloxan-injected groups were treated with metformin (100 mg/kg body weight) as a reference drug (G3), or fed on basal diet supplemented with 5% of either Sidr fruits (SFP) or leaves powder (SLP) (G4 and G5, respectively). G6 and G7 received combined treatments (metformin + SFP and metformin + SLP, respectively). The curative period lasted for 4 weeks. By its end, body weight gain (BWG) and relative weights of liver, kidneys and pancreas were calculated. Fasting glucose, insulin, amylase activity, liver glycogen, lipid profile as well as liver and kidney functions were determined. The typical manifestations of diabetes were noticed in untreated diabetic group including hyperglycemia and hypoinsulinemia.Moreover, a significant increase in serum amylase activity and relative liver and kidney weights was noticed associated with dyslipidemia, liver and kidney dysfunction and a significant decrease in BWG and absolute pancreas weight along with marked histopathological abnormalities in pancreas tissue.SFP was more effective than SLP in normalizing body weight, pancreas weight and liver antioxidant status, while the capability of SLP was higher in correcting the level of serum low density lipoprotein cholesterol (bad cholesterol). In general, receiving combined treatments was more efficient than receiving metformin alone.In conclusion, Sidr fruits and leaves can help metformin in the treatment of diabetes mellitus.

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Section: Discussionsupporting

confidence: 50%

Co-therapeutic effects of metformin and Sidr fruits and leaves in experimental diabetic rats

El-Hashash

2020

Egyptian Journal of Nutrition and Health

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“…With changes in diet, bone cells can adversely affect the skeletal system by altering the activity of glucocorticoid levels causing muscle wasting, osteoporosis, and insulin resistance [42]. A large number of studies have shown that secondary osteoporosis, muscle atrophy, insulin resistance, and type 2 diabetes caused by excessive glucocorticoid in skeletal muscle are mainly caused by high-fat diets [43]. For example, the increase of glucocorticoids in skeletal muscle caused by high-fat diets is due to the increase of free fatty acids in the blood circulation, which inhibits the synthesis of protein, resulting in a negative nitrogen balance in skeletal muscle, thus causing muscle atrophy [44,45].…”

Section: Discussionmentioning

confidence: 99%

Untargeted Metabolomic Characteristics of Skeletal Muscle Dysfunction in Rabbits Induced by a High Fat Diet

Fan

Wang

et al. 2021

Animals

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Type 2 diabetes and metabolic syndrome caused by a high fat diet (HFD) have become public health problems worldwide. These diseases are characterized by the oxidation of skeletal muscle mitochondria and disruption of insulin resistance, but the mechanisms are not well understood. Therefore, this study aims to reveal how high-fat diet causes skeletal muscle metabolic disorders. In total, 16 weaned rabbits were randomly divided into two groups, one group was fed a standard normal diet (SND) and the other group was fed a high fat diet (HFD) for 5 weeks. At the end of the five-week experiment, skeletal muscle tissue samples were taken from each rabbit. Untargeted metabolomic analysis was performed using ultra-performance liquid chromatography combined with mass spectrometry (UHPLC-MS/MS). The results showed that high fat diet significantly altered the expression levels of phospholipids, LCACs, histidine, carnosine, and tetrahydrocorticosterone in skeletal muscle. Principal component analysis (PCA) and least squares discriminant analysis (PLS-DA) showed that, compared with the SND group, skeletal muscle metabolism in HFD group was significantly up-regulated. Among 43 skeletal muscle metabolites in the HFD group, phospholipids, LCACs, histidine, carnosine, and tetrahydrocorticosteroids were identified as biomarkers of skeletal muscle metabolic diseases, and may become potential physiological targets of related diseases in the future. Untargeted metabonomics analysis showed that high-fat diet altered the metabolism of phospholipids, carnitine, amino acids and steroids in skeletal muscle of rabbits. Notably, phospholipids, LCACs, histidine, carnopeptide, and tetrahydrocorticosteroids block the oxidative capacity of mitochondria and disrupt the oxidative capacity of glucose and the fatty acid-glucose cycle in rabbit skeletal muscle.

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“…It is believed that the use of such concentration, in contrast to high-fructose (60-70%), more closely corresponds to the picture of IR in humans and is sufficient for the manifestation of major metabolic disorders in experimental animals (Wong et al 2016). Animals of group 3 -was the correction of the drug "Metformin" and group 4 -was the correction of lyophilized DBH powder (LLC "Natural Beauty", Ukraine) on the background of fructose load, starting from 6 weeks of MetS modeling, began to be administered intragastrically with a probe in the form of a water solution of metformin for 14 days (therapeutic and prophylactic mode of administration) and lyophilized DBH powder (groups 4), respectively (Barthem et al 2019;Mengsiyu et al 2019).…”

Section: Methodsmentioning

confidence: 99%

Preclinical safety evaluation of drone brood homogenate and justification of pharmacological action

Pavliuk¹,

Stechyshyn²,

Chubka³

et al. 2021

PHAR

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The problem of studying the metabolic syndrome, as well as its integration into other pathological processes, despite large-scale research, remains relevant. The complexity of the interaction of different links in pathogenesis requires scientists to find new tools and methods for both diagnosis and treatment. Drone brood homogenate, which is a multifactorial pharmacological agent in terms of chemical composition, seems to be promising to study for today. And the lack of contraindications and a wide age range makes it an excellent object of research. The current study evaluated the pharmacological aspects of safety: acute toxicity, effects on the functional and motor activity of the gastrointestinal tract, as well as local irritation of the gastric mucosa, the secretory function of the stomach. All experiments were performed according to the classical methods. The specific pharmacological activity of the drone brood homogenate was determined in comparison with metformin in the experimental fructose metabolic syndrome. Animals obtained from the Vivarium of I.Horbachevsky Ternopil National Medical University were used to implement the set goals. Working with animals was met all bioethical requirements. The study found that the lyophilized drone brood homogenate does not have a local irritant effect and does not cause ulcers on the surface of the gastric mucosa, does not affect the secretory function of the stomach and motor-evacuatory activity of the gastrointestinal tract and is a low-toxic substance, indicating the possibility of its long-term safe use. As expected, glucose, insulin, and HOMA index were significantly increased in animals that were simulated metabolic syndrome. The use of drone brood homogenate by animals contributed to a relatively positive effect on selected indicators of the metabolic syndrome. Accordingly, drone brood homogenate is a promising active pharmaceutical ingredient for the normalization of biochemical disorders in metabolic syndrome.

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A Possible Mechanism of Metformin in Improving Insulin Resistance in Diabetic Rat Models

Cited by 15 publications

References 29 publications

Co-therapeutic effects of metformin and Sidr fruits and leaves in experimental diabetic rats

Co-therapeutic effects of metformin and Sidr fruits and leaves in experimental diabetic rats

Untargeted Metabolomic Characteristics of Skeletal Muscle Dysfunction in Rabbits Induced by a High Fat Diet

Preclinical safety evaluation of drone brood homogenate and justification of pharmacological action

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