Deep sea minerals prolong life span of streptozotocin-induced diabetic rats by compensatory augmentation of the IGF-I-survival signaling and inhibition of apoptosis

Environ Toxicol. 2016 Jul;31(7):769-81. doi: 10.1002/tox.22086. Epub 2015 Mar 2.


Consumption of deep sea minerals (DSM), such as magnesium, calcium, and potassium, is known to reduce hypercholesterolemia-induced myocardial hypertrophy and cardiac-apoptosis and provide protection against cardiovascular diseases. Heart diseases develop as a lethal complication among diabetic patients usually due to hyperglycemia-induced cardiac-apoptosis that causes severe cardiac-damages, heart failure, and reduced life expectancy. In this study, we investigated the potential of DSM and its related cardio-protection to increase the life expectancy in diabetic rats. In this study, a heart failure rat model was developed by using streptozotocin (65 mg kg(-1) ) IP injection. Different doses of DSM-1× (37 mg kg(-1) day(-1) ), 2× (74 mg kg(-1) day(-1) ) and 3× (111 mg kg(-1) day(-1) ), were administered to the rats through gavages for 4 weeks. The positive effects of DSM on the survival rate of diabetes rats were determined with respect to the corresponding effects of MgSO4 . Further, to understand the mechanism by which DSM enhances the survival of diabetic rats, their potential to regulate cardiac-apoptosis and control cardiac-dysfunction were examined. Echocardiogram, tissue staining, TUNEL assay, and Western blotting assay were used to investigate modulations in the myocardial contractile function and related signaling protein expression. The results showed that DSM regulate apoptosis and complement the cardiomyocyte proliferation by enhancing survival mechanisms. Moreover DSM significantly reduced the mortality rate and enhanced the survival rate of diabetic rats. Experimental results show that DSM administration can be an effective strategy to improve the life expectancy of diabetic subjects by improving cardiac-cell proliferation and by controlling cardiac-apoptosis and associated cardiac-dysfunction. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 769-781, 2016.

Keywords: IGFI; cardiac-apoptosis; cardiac-dysfunction; deep sea minerals; diabetes mellitus.

MeSH terms

  • Animals
  • Apoptosis / drug effects*
  • Blood Glucose / metabolism
  • Cell Proliferation / drug effects
  • Diabetes Mellitus, Experimental / complications
  • Diabetes Mellitus, Experimental / drug therapy*
  • Diabetes Mellitus, Experimental / pathology
  • Echocardiography
  • Heart Failure / etiology
  • Heart Failure / pathology
  • Heart Failure / prevention & control
  • Insulin-Like Growth Factor I / drug effects*
  • Longevity / drug effects*
  • Magnesium Sulfate / pharmacology
  • Male
  • Minerals / chemistry
  • Minerals / therapeutic use*
  • Myocytes, Cardiac / drug effects
  • Myocytes, Cardiac / pathology
  • Rats
  • Rats, Sprague-Dawley
  • Seawater / chemistry*
  • Signal Transduction
  • Survival Analysis


  • Blood Glucose
  • Minerals
  • Insulin-Like Growth Factor I
  • Magnesium Sulfate