Abstract

In this study, we investigated the effects of balanced deep-sea water (BDSW) on hyperglycemia and glucose intolerance in high-fat diet (HFD)-induced diabetic C57BL/6J mice. BDSW was prepared by mixing deep-sea water (DSW) mineral extracts and desalinated water to give a final hardness of 500–2000. Mice given an HFD with BDSW showed lowered fasting plasma glucose levels compared to HFD-fed mice. Oral and intraperitoneal glucose tolerance tests showed that BDSW improves impaired glucose tolerance in HFD-fed mice. Histopathological evaluation of the pancreas showed that BDSW recovers the size of the pancreatic islets of Langerhans, and increases the secretion of insulin and glucagon in HFD-fed mice. Quantitative reverse transcription polymerase chain reaction results revealed that the expression of hepatic genes involved in glucogenesis, glycogenolysis and glucose oxidation were suppressed, while those in glucose uptake, β-oxidation, and glucose oxidation in muscle were increased in mice fed HFD with BDSW. BDSW increased AMP-dependent kinase (AMPK) phosphorylation in 3T3-L1 pre- and mature adipocytes and improved impaired AMPK phosphorylation in the muscles and livers of HFD-induced diabetic mice. BDSW stimulated phosphoinositol-3-kinase and AMPK pathway-mediated glucose uptake in 3T3-L1 adipocytes. Taken together, these results suggest that BDSW has potential as an anti-diabetic agent, given its ability to suppress hyperglycemia and improve glucose intolerance by increasing glucose uptake.

Highlights

  • Type 2 diabetes is characterized by insulin resistance, hyperglycemia, and progressive beta-cell dysfunction, which leads to multiple diabetic complications like nephropathy, neuropathy, retinopathy, and ketoacidosis

  • To determine the effect of balanced deep-sea water (BDSW) on the development of diabetes, we investigated fasting blood glucose levels and glucose tolerance in high-fat diet (HFD)-induced diabetic mice

  • Our findings showed the characteristics of obese type 2 diabetes such as hyperglycemia, glucose intolerance, and increased weight gain in HFD-induced

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Summary

Introduction

Type 2 diabetes is characterized by insulin resistance, hyperglycemia, and progressive beta-cell dysfunction, which leads to multiple diabetic complications like nephropathy, neuropathy, retinopathy, and ketoacidosis. As an alternative strategy for developing effective and safe anti-diabetes drugs, many natural products, including crude extracts and compounds that have been isolated from natural resources, are being investigated to treat diabetes [5]. In vivo [15] and in vitro [16] studies showed that DSW (hardness 1000 ppm) has anti-obesity and anti-diabetic properties, including inhibition of adipocyte differentiation and lipid accumulation, as well as anti-hyperglycemic activity. It is worth studying the possibility that BDSW with high Mg and Ca content might be a new agent for treating or preventing metabolic disease. To investigate the effect of balanced deep-sea water (BDSW), of differing hardness, on obese type 2 diabetic mice, our study used BDSW ranging from relatively low (500 ppm) to high (2000 ppm) hardness. Development of type 2 diabetes in vivo, we examined fasting blood glucose levels and glucose tolerance in C57BL/6 mice that exhibited type 2 diabetes induced by high-fat diet feeding

Results and Discussion
BDSW Activates the PI-3K and AMPK Signaling Pathways
BDSW Specifically Stimulates AMPK Phosphorylation and Improves Impaired AMPK
Materials
The Preparatioin of BDSW
Animals and Diets
Determination of Blood Glucose Level
Cell Culture and Adipocyte Differentiation
Triglyceride and Cholesterol Assays of the Liver and Serum
Histopathological Analysis of Pancreas
Determination of Glucose Uptake by 3T3-L1 Adipocytes
3.10. Western Blot Analysis
3.12. Statistical Analysis
Conclusions
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