Pleiotropic effects of metformin in managing type 2 diabetes and metabolic syndrome: Evidences from experimental mouse model.

Christina Gertrude Yap, Rakesh Naidu, Kim Dae Jin, Srinivasa Sirasanagandla, Narendra Pamidi

Research output: Contribution to journalArticle

Abstract

Background: Metformin is the common first-line medication for treating type 2 diabetes. Besides its anti-hyperglycemic property, various studies have isolatedly shown its effectiveness in reducing body weight and ameliorated components of metabolic syndrome. However, it has not been evidently shown weather metformin is effective as a dual treatment in cases of diet induced obesity and diabetes. We optimized a mouse model for diet induced obesity and diabetes for evaluating dual effectiveness of metformin in treating obesity and diabetes and simultaneously demonstrated histological changes in obese and diabetic kidney and heart tissues and the cellular-protective effects of metformin on these tissues. Methods: BULB/c mice were fed with normal, high fat or high sucrose diets for 26 w. All groups were treated with metformin from w 16 to 26. Blood samples were collected and body weights recorded on d 1 and forth nightly till w 26 when all animals were sacrificed. Hearts and kidneys were dissected and prepared for historical observation. Blood samples were processed accordingly for quantitating blood glucose, ROS and ROS defense (d 1 and d 182). Results: HFD and HSS feeds successfully created diet induced by obesity and diabetes by w 15. Metformin significantly lowered the average body weight of obese group (p<0.05) as well as the average blood glucose levels of the diabetes group (p<0.005) relative to the respective control groups. Histological studies showed no morphological cellular changes in heart and kidney tissues of obese and diabetic mice relative to respective controls (untreated). Cell shrinkage/‘sick cells” were seen in the untreated obese and diabetic mice. ROS levels in the metformin treated mice remained normal relative to the untreated control groups (p<0.05). Conclusions: We have optimized a reliable mouse model for obesity and diabetes. Metformin is effective for controlling diet induced obesity and diabetes. Metformin also showed protection against obesity and hyperglycemia related cell morphological changes.

Original languageEnglish
Pages (from-to)3323-3335
Number of pages13
JournalBiomedical Research (India)
Volume29
Issue number17
DOIs
Publication statusPublished - Jan 1 2018

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Metformin
Medical problems
Type 2 Diabetes Mellitus
Theoretical Models
Obesity
Nutrition
Diet
Obese Mice
Body Weight
Tissue
Kidney
Blood Glucose
Blood
Control Groups
Weather
Hyperglycemia
Sucrose
Animals
Fats
Observation

Keywords

  • Cellular changes
  • Diet induced obesity
  • Dual treatment
  • Metformin
  • Type 2 diabetes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Pleiotropic effects of metformin in managing type 2 diabetes and metabolic syndrome : Evidences from experimental mouse model. / Yap, Christina Gertrude; Naidu, Rakesh; Jin, Kim Dae; Sirasanagandla, Srinivasa; Pamidi, Narendra.

In: Biomedical Research (India), Vol. 29, No. 17, 01.01.2018, p. 3323-3335.

Research output: Contribution to journalArticle

Yap, Christina Gertrude ; Naidu, Rakesh ; Jin, Kim Dae ; Sirasanagandla, Srinivasa ; Pamidi, Narendra. / Pleiotropic effects of metformin in managing type 2 diabetes and metabolic syndrome : Evidences from experimental mouse model. In: Biomedical Research (India). 2018 ; Vol. 29, No. 17. pp. 3323-3335.
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T1 - Pleiotropic effects of metformin in managing type 2 diabetes and metabolic syndrome

T2 - Evidences from experimental mouse model.

AU - Yap, Christina Gertrude

AU - Naidu, Rakesh

AU - Jin, Kim Dae

AU - Sirasanagandla, Srinivasa

AU - Pamidi, Narendra

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AB - Background: Metformin is the common first-line medication for treating type 2 diabetes. Besides its anti-hyperglycemic property, various studies have isolatedly shown its effectiveness in reducing body weight and ameliorated components of metabolic syndrome. However, it has not been evidently shown weather metformin is effective as a dual treatment in cases of diet induced obesity and diabetes. We optimized a mouse model for diet induced obesity and diabetes for evaluating dual effectiveness of metformin in treating obesity and diabetes and simultaneously demonstrated histological changes in obese and diabetic kidney and heart tissues and the cellular-protective effects of metformin on these tissues. Methods: BULB/c mice were fed with normal, high fat or high sucrose diets for 26 w. All groups were treated with metformin from w 16 to 26. Blood samples were collected and body weights recorded on d 1 and forth nightly till w 26 when all animals were sacrificed. Hearts and kidneys were dissected and prepared for historical observation. Blood samples were processed accordingly for quantitating blood glucose, ROS and ROS defense (d 1 and d 182). Results: HFD and HSS feeds successfully created diet induced by obesity and diabetes by w 15. Metformin significantly lowered the average body weight of obese group (p<0.05) as well as the average blood glucose levels of the diabetes group (p<0.005) relative to the respective control groups. Histological studies showed no morphological cellular changes in heart and kidney tissues of obese and diabetic mice relative to respective controls (untreated). Cell shrinkage/‘sick cells” were seen in the untreated obese and diabetic mice. ROS levels in the metformin treated mice remained normal relative to the untreated control groups (p<0.05). Conclusions: We have optimized a reliable mouse model for obesity and diabetes. Metformin is effective for controlling diet induced obesity and diabetes. Metformin also showed protection against obesity and hyperglycemia related cell morphological changes.

KW - Cellular changes

KW - Diet induced obesity

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KW - Metformin

KW - Type 2 diabetes

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