Skip to main content
×
Home
    • Aa
    • Aa

Up-regulation of PPARγ, heat shock protein-27 and -72 by naringin attenuates insulin resistance, β-cell dysfunction, hepatic steatosis and kidney damage in a rat model of type 2 diabetes

  • Ashok Kumar Sharma (a1), Saurabh Bharti (a1), Shreesh Ojha (a1), Jagriti Bhatia (a1), Narender Kumar (a2), Ruma Ray (a2), Santosh Kumari (a3) and Dharamvir Singh Arya (a1)...
Abstract

Naringin, a bioflavonoid isolated from grapefruit, is well known to possess lipid-lowering and insulin-like properties. Therefore, we assessed whether naringin treatment ameliorates insulin resistance (IR), β-cell dysfunction, hepatic steatosis and kidney damage in high-fat diet (HFD)–streptozotocin (STZ)-induced type 2 diabetic rats. Wistar albino male rats were fed a HFD (55 % energy from fat and 2 % cholesterol) to develop IR and on the 10th day injected with a low dose of streptozotocin (40 mg/kg, intraperitoneal (ip)) to induce type 2 diabetes. After confirmation of hyperglycaemia (>13·89 mmol/l) on the 14th day, different doses of naringin (25, 50 and 100 mg/kg per d) and rosiglitazone (5 mg/kg per d) were administered orally for the next 28 d while being maintained on the HFD. Naringin significantly decreased IR, hyperinsulinaemia, hyperglycaemia, dyslipidaemia, TNF-α, IL-6, C-reactive protein and concomitantly increased adiponectin and β-cell function in a dose-dependent manner. Increased thiobarbituric acid-reactive substances and decreased antioxidant enzyme activities in the serum and tissues of diabetic rats were also normalised. Moreover, naringin robustly increased PPARγ expression in liver and kidney; phosphorylated tyrosine insulin receptor substrate 1 in liver; and stress proteins heat shock protein (HSP)-27 and HSP-72 in pancreas, liver and kidney. In contrast, NF-κB expression in these tissues along with sterol regulatory element binding protein-1c and liver X receptor- expressions in liver were significantly diminished. In addition, microscopic observations validated that naringin effectively rescues β-cells, hepatocytes and kidney from HFD-STZ-mediated oxidative damage and pathological alterations. Thus, this seminal study provides cogent evidence that naringin ameliorates IR, dyslipidaemia, β-cell dysfunction, hepatic steatosis and kidney damage in type 2 diabetic rats by partly regulating oxidative stress, inflammation and dysregulated adipocytokines production through up-regulation of PPARγ, HSP-27 and HSP-72.

  • View HTML
    • Send article to Kindle

      To send this article to your Kindle, first ensure coreplatform@cambridge.org is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about sending to your Kindle.

      Note you can select to send to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

      Find out more about the Kindle Personal Document Service.

      Up-regulation of PPARγ, heat shock protein-27 and -72 by naringin attenuates insulin resistance, β-cell dysfunction, hepatic steatosis and kidney damage in a rat model of type 2 diabetes
      Available formats
      ×
      Send article to Dropbox

      To send this article to your Dropbox account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your Dropbox account. Find out more about sending content to Dropbox.

      Up-regulation of PPARγ, heat shock protein-27 and -72 by naringin attenuates insulin resistance, β-cell dysfunction, hepatic steatosis and kidney damage in a rat model of type 2 diabetes
      Available formats
      ×
      Send article to Google Drive

      To send this article to your Google Drive account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your Google Drive account. Find out more about sending content to Google Drive.

      Up-regulation of PPARγ, heat shock protein-27 and -72 by naringin attenuates insulin resistance, β-cell dysfunction, hepatic steatosis and kidney damage in a rat model of type 2 diabetes
      Available formats
      ×
Copyright
Corresponding author
*Corresponding author: D. S. Arya, fax +91 11 26584121, email dsarya16@hotmail.com
Linked references
Hide All

This list contains references from the content that can be linked to their source. For a full set of references and notes please see the PDF or HTML where available.

1JE Shaw , RA Sicree & PZ Zimmet (2010) Global estimates of the prevalence of diabetes for 2010 and 2030. Diabetes Res Clin Pract 87, 414.

2GS Hotamisligil (2006) Inflammation and metabolic disorders. Nature 444, 860867.

3KE Wellen & GS Hotamisligil (2005) Inflammation, stress, and diabetes. J Clin Invest 115, 11111119.

4EJ Koning , S Bonner-Weir & TJ Rabelink (2008) Preservation of beta-cell function by targeting beta-cell mass. Trends Pharmacol Sci 29, 218227.

5EE Mulvihill , EM Allister , BG Sutherland , (2009) Naringenin prevents dyslipidemia, apolipoprotein B overproduction, and hyperinsulinemia in LDL receptor-null mice with diet-induced IR. Diabetes 58, 21982210.

6S Furukawa , T Fujita , M Shimabukuro , (2004) Increased oxidative stress in obesity and its impact on metabolic syndrome. J Clin Invest 114, 17521761.

9SM Jeon , YB Park & MS Choi (2004) Antihypercholesterolemic property of naringin alters plasma and tissue lipids, cholesterol regulating enzymes, fecal sterol and tissue morphology in rabbits. Clin Nutr 23, 10251034.

10HJ Kim , GT Oh , YB Park , (2004) Naringin alters the cholesterol biosynthesis and antioxidant enzyme activities in LDL receptor-knockout mice under cholesterol fed condition. Life Sci 74, 16211634.

11UJ Jung , MK Lee , YB Park , (2006) Effect of citrus flavonoids on lipid metabolism and glucose-regulating enzyme mRNA levels in type-2 diabetic mice. Int J Biochem Cell Biol 38, 11341145.

12A Aggarwal , V Gaur & A Kumar (2010) Nitric oxide mechanism in the protective effect of naringin against post-stroke depression (PSD) in mice. Life Sci 86, 928935.

13L Michalik & W Wahli (2006) Involvement of PPAR nuclear receptors in tissue injury and wound repair. J Clin Invest 116, 598606.

14H Yki-Jarvinen (2004) Thiazolidinediones. N Engl J Med 351, 11061118.

15J Chung , AK Nguyen , DC Henstridge , (2008) HSP72 protects against obesity-induced IR. Proc Natl Acad Sci USA 105, 17391744.

16KK Meldrum , AL Burnett , X Meng , (2003) Liposomal delivery of heat shock protein 72 into renal tubular cells blocks nuclear factor-kappaB activation, tumor necrosis factor-alpha production, and subsequent ischemia-induced apoptosis. Circ Res 92, 293299.

18DR Matthews , JP Hosker , AS Rudenski , (1985) Homeostasis model assessment: IR and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 28, 412419.

19H Ohkawa , N Oohishi & N Yagi (1979) Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem 95, 351358.

20S Marklund & G Marklund (1974) Involvement of the superoxide anion radical in the autoxidation of pyrogallol and a convenient assay for superoxide dismutase. Eur J Biochem 47, 469474.

21RA Lawrence & RF Burk (1976) Glutathione peroxidase activity in selenium-deficient rat liver. Biochem Biophys Res Commun 71, 952958.

22MM Bradford (1976) A rapid and sensitive method for quantization of microgram quantities effects of age and caloric restriction. Anal Biochem 72, 248254.

23A Jang , P Srinivasan , NY Lee , (2008) Comparison of hypolipidemic activity of synthetic gallic acid-linoleic acid ester with mixture of gallic acid and linoleic acid, gallic acid, and linoleic acid on high-fat diet induced obesity in C57BL/6Cr Slc mice. Chem Biol Interact 174, 109117.

24RS Danda , NM Habiba , H Rincon-Choles , (2005) Kidney involvement in a nongenetic rat model of type 2 diabetes. Kidney Int 68, 25622571.

25K Srinivasan , B Viswanad , L Asrat , (2005) Combination of high-fat diet-fed and low-dose streptozotocin-treated rat: a model for type 2 diabetes and pharmacological screening. Pharmacol Res 52, 313320.

26K Parveen , MR Khan , M Mujeeb , (2010) Protective effects of Pycnogenol on hyperglycemia-induced oxidative damage in the liver of type 2 diabetic rats. Chem Biol Interact 186, 219227.

28RI Morimoto (1993) Cells in stress: transcriptional activation of heat shock genes. Science 259, 14091410.


31CM Taniguchi , K Ueki & R Kahn (2005) Complementary roles of IRS-1 and IRS-2 in the hepatic regulation of metabolism. J Clin Invest 115, 718727.

32A Ceriello & E Motz (2004) Is oxidative stress the pathogenic mechanism underlying IR, diabetes, and cardiovascular disease? The common soil hypothesis revisited. Arterioscler Thromb Vasc Biol 24, 816823.

33MR Taskinen (2003) Diabetic dyslipidaemia: from basic research to clinical practice. Diabetologia 46, 733749.

34I Alvarez-González , E Madrigal-Bujaidar , V Dorado , (2001) Inhibitory effect of naringin on the micronuclei induced by ifosfamide in mouse, and evaluation of its modulatory effect on the Cyp3a subfamily. Mutat Res 480-481, 171178.

Recommend this journal

Email your librarian or administrator to recommend adding this journal to your organisation's collection.

British Journal of Nutrition
  • ISSN: 0007-1145
  • EISSN: 1475-2662
  • URL: /core/journals/british-journal-of-nutrition
Please enter your name
Please enter a valid email address
Who would you like to send this to? *
×

Keywords: