Sunmin Park

Antidiabetic effects of fermented soybean products on type 2 diabetes

Historically, the incidence of type 2 diabetes has been lower in Asian populations compared with those in Western countries. One possible reason for the lower incidence among Asians is that they consume fermented soybean products, which are unique to the traditional Asian diet. Some have hypothesized that dietary phytoestrogens and soy peptides in fermented soybean foods consumed in traditional Asian diets may help prevent and slow the progression of type 2 diabetes. This review evaluates the existing evidence from animal studies and clinical and epidemiologic investigations on fermented soybeans in the prevention and treatment of type 2 diabetes. Nutritional studies performed in animals and intervention studies with humans suggest that the ingestion of soy protein with isoflavones improves glucose control and reduces insulin resistance. Korean fermented soybean products such as doenjang, kochujang, and chungkookjang contain alterations in the structures and content of isoflavonoids and small bioactive peptides, which are produced during fermentation. Several studies revealed improvements in insulin resistance and insulin secretion with the consumption of these fermented products. Therefore, fermented soybean products may help prevent or attenuate the progression of type 2 diabetes. Although the lack of human intervention trials does not permit definitive conclusions, the evidence does suggest that fermented soy products may be better for preventing or delaying the progression of type 2 diabetes compared with nonfermented soybeans.

Improvement of Insulin Resistance and Insulin Secretion by Water Extracts of Cordyceps militaris, Phellinus linteus, and Paecilomyces tenuipes in 90% Pancreatectomized Rats

The effect of supplementation with Phellinus linteus (P. linteus), Paecilomyces tenuipes (P. tenuipes), and Cordyceps militaris (C. militaris) mushroom water extracts on the insulin secretion and insulin resistance of 90% pancreatectomized (Px) male Sprague Dawley rats was investigated. Px rats were daily administered 0.5 g of P. linteus, P. tenuipes, and C. militaris aqueous extracts or a placebo per 1 kg body weight with a 40% fat diet for 8 weeks. Fasting serum glucose levels were lower in rats receiving C. militaris than in the control group. Insulin secretion at the elevated serum glucose levels was lowest in rats that consumed P. tenuipes in hyperglycemic clamp. Whole body glucose disposal rates increased in C. militaris but decreased in P. tenuipes compared to those in the control group in euglycemic hyperinsulinemic clamp. The GLUT4 content and fraction velocity of glycogen synthase in the soleus and quadriceps muscles increased in the rats treated with C. militaris, but P. tenuipes decreased both. In sum, a water extract of C. militaris ameliorates insulin resistance by enhancing glucose utilization in skeletal muscles.

Ginsenosides Rb1 and Rg1 Suppress Triglyceride Accumulation in 3T3-L1 Adipocytes and Enhance β-Cell Insulin Secretion and Viability in Min6 Cells via PKA-Dependent Pathways

Ginseng root is known to induce anti-diabetic activity, but the key components involved are unknown. We investigated which major ginsenosides in ginseng enhanced glucose homeostasis by in vitro studies. Rb1 and Rg1 reduced the triglyceride accumulation in 3T3-L1 adipocytes by activating PKA with increased intracellular cAMP. However, the insulin-stimulated glucose uptake was enhanced by Rb1 and Rg1 via activation of phosphatidylinositol-3 kinase. Rb1 and Rg1 promoted glucose-stimulated insulin secretion and cell viability in Min6 cells through PKA which augmented IRS2 expression to enhance insulin/IGF-1 signaling. These results suggest that Rb1 and Rg1 improved glucose homeostasis through the activation of a PKA like glucagon-like peptide-1 receptor agonist.

Inappropriate Survey Design Analysis of the Korean National Health and Nutrition Examination Survey May Produce Biased Results

Objectives The inherent nature of the Korean National Health and Nutrition Examination Survey (KNHANES) design requires special analysis by incorporating sample weights, stratification, and clustering not used in ordinary statistical procedures. Methods This study investigated the proportion of research papers that have used an appropriate statistical methodology out of the research papers analyzing the KNHANES cited in the PubMed online system from 2007 to 2012. We also compared differences in mean and regression estimates between the ordinary statistical data analyses without sampling weight and design-based data analyses using the KNHANES 2008 to 2010. Results Of the 247 research articles cited in PubMed, only 19.8% of all articles used survey design analysis, compared with 80.2% of articles that used ordinary statistical analysis, treating KNHANES data as if it were collected using a simple random sampling method. Means and standard errors differed between the ordinary statistical data analyses and design-based analyses, and the standard errors in the design-based analyses tended to be larger than those in the ordinary statistical data analyses. Conclusions Ignoring complex survey design can result in biased estimates and overstated significance levels. Sample weights, stratification, and clustering of the design must be incorporated into analyses to ensure the development of appropriate estimates and standard errors of these estimates.

Isoflavonoids and peptides from meju, long-term fermented soybeans, increase insulin sensitivity and exert insulinotropic effects in vitro

OBJECTIVE Although soybeans have been shown to alleviate metabolic syndromes, fermented soybeans may have even greater effects. We investigated the antidiabetic effects of meju, a soy food that is fermented up to 2 mo, and the mechanism by which it exerts its effects. METHODS Meju was prepared by a traditional fermentation process: soybeans were fermented outdoors for 20 or 60 d. Methanol (M-60) and water (W-60) extracts from meju that had fermented for 60 d contained mostly isoflavonoid aglycones and small peptides, respectively, as opposed to mostly glycosylated isoflavonoids and proteins in the original soybeans. RESULTS Daidzein, M-60, and W-60 had better insulin-sensitizing actions by activating peroxisome proliferator-activated receptor-γ in 3T3-L1 adipocytes than did unfermented soybeans. In addition, Min6 insulinoma cells treated with genistein, M-60, and W-60 had greater glucose-stimulated insulin secretion capacity and greater β-cell viability than those treated with unfermented soybeans. This improvement was associated with insulin/insulin-like growth factor-1 signaling that was activated by the tyrosine phosphorylation of insulin receptor substrate-2 and serine phosphorylation of Akt, and this in turn increased pancreatic and duodenal homeobox-1 expression. Furthermore, genistein, daidzein, and M-60 stimulated glucagon-like peptide-1 secretion in enteroendocrine NCI-H716 cells, which generated insulinotropic actions. CONCLUSION The compositional changes in isoflavonoids and peptides that occurred during a longer fermentation period, without the use of salt, enhanced the antidiabetic effect of soybeans.

Probiotics for weight loss: a systematic review and meta-analysis

The intestinal microbiota has been reported to be one of the potential determinants of obesity in recent human and animal studies. Probiotics may affect the gut microbiota to modulate obesity. This systematic review aims to summarize and critically evaluate the evidence from clinical trials that have tested the effectiveness of probiotics or foods containing probiotics as a treatment for weight loss. Literature searches of electronic databases such as PubMed, Cochrane Library, and EMBASE were conducted. Methodological quality was assessed using body weight and body mass index (BMI). Initial searches yielded 368 articles. Of these, only 9 met the selection criteria. Because of insufficient data, only 4 of the studies were randomized controlled trials (RCTs) that compared the therapeutic efficacy of probiotics with placebo. The meta-analysis of these data showed no significant effect of probiotics on body weight and BMI (body weight, n = 196; mean difference, -1.77; 95% confidence interval, -4.84 to 1.29; P = .26; BMI, n = 154; mean difference, 0.77; 95% confidence interval, -0.24 to 1.78; P = .14). However, the total number of RCTs included in the analysis, the total sample size, and the methodological quality of the primary studies were too low to draw definitive conclusions. Thus, more rigorously designed RCTs are necessary to examine the effect of probiotics on body weight in greater detail. Collectively, the RCTs examined in this meta-analysis indicated that probiotics have limited efficacy in terms of decreasing body weight and BMI and were not effective for weight loss.

Induction of long-term normoglycemia without medication in Korean type 2 diabetes patients after continuous subcutaneous insulin infusion therapy.

Our previous studies showed that some Korean type 2 diabetic patients could maintain long‐term normal blood glucose control without any medication, referred to as remission after a certain period of normalization of blood glucose level by continuous subcutaneous insulin infusion (CSII) treatment. In this study we determined the clinical characteristics that influenced the induction of remission.

Vitamin D deficiency is an independent risk factor for cardiovascular disease in Koreans aged ≥ 50 years: results from the Korean National Health and Nutrition Examination Survey

Vitamin D deficiency is a risk factor for metabolic syndromes. We examined whether vitamin D deficiency altered the prevalence of cardiovascular disease (CVD) in older Koreans. Cross-sectional analysis of data from the Korean National Health and Nutrition Examination Survey IV 2008-2009 was used to examine the association between serum 25-hydroxyvitamin D (25(OH)D) levels and the prevalence of CVD in a representative population-based sample of 5,559 men and women aged ≥ 50 years. CVD was defined as angina pectoris, myocardial infarction, or stroke. The prevalence of CVD (7.0%) in the older Korean population was lower than that in the older US population, although average serum 25(OH)D levels were much lower in the Korean population. Additionally, serum 25(OH)D levels did not differ significantly between the CVD and non-CVD groups. However, subjects in the lowest category (< 25 nmol/l) of serum 25(OH)D level had the greatest prevalence of CVD, about two-fold higher than subjects in the highest category (> 75 nmol/l), after adjusting for age, gender, body mass index, education level, residence location, and region. The prevalence of other risk factors for CVD, including higher waist circumference, fasting glucose, low-density lipoprotein (LDL) cholesterol, and triglyceride levels and lower high-density lipoprotein (HDL) cholesterol levels, was also higher among subjects in the lowest category than among those in the highest category. In conclusion, low serum 25(OH)D may be an independent risk factor for CVD in older Koreans.

The lignan-rich fractions of Fructus Schisandrae improve insulin sensitivity via the PPAR-γ pathways in in vitro and in vivo studies

ETHNOPHARMACOLOGICAL RELEVANCE Fructus Schisandrae, the fruit of Schisandra chinensis (Turcz.) Baillon, has been traditionally used as a hypoglycemic agent in Asia and its extracts have been shown to improve insulin-stimulated glucose uptake in cell-based assays in previous studies. AIM OF THE STUDY We set out to determine which fractions of Fructus Schisandrae improved peroxisome proliferator-activated receptor (PPAR)-γ activity and glucose-stimulated insulin secretion in cell-based experiments. The fractions that enhance glucose homeostasis were then tested for their hypoglycemic effects and mechanism was examined. MATERIALS AND METHODS The fractions (FS-0, FS-20, FS-40, FS-60, FS-80, FS-100) were made by extracting Fructus Schisandrae with 70% ethanol followed by its fractionation with a XDA column with a different ratio of methanol and water. The insulin-stimulated glucose uptake and PPAR-γ agonistic actions of each fraction were investigated in 3T3-L1 adipocytes and glucose-stimulated insulin secretion was determined in Min6 cells. The fraction(s) that were efficacious (200mg/kg bw) were orally given to 90% pancreatectomized (Px) diabetic rats for 8 weeks to evaluate insulin sensitivity in euglycemic hyperinsulinemic clamp and insulin secretion at hyperglycemic clamp. RESULTS FS-60 contains schizandrin, gomisin A and angeloylgomisin H while FS-80 contains deoxyschizandrin, γ-schizandrin, and gomisin N. A PPAR-γ agonistic action was greater in the ascending order of the control, FS-80 and FS-60 in 3T3-L1 adipocytes. FS-60 increased the glucose disposal rates of Px rats as much as rosiglitazone during euglycemic hyperinsulinemic clamp while hepatic glucose output at hyperinsulinemic clamped states decreased in the descending order of the control, FS-80, FS-60 with potentiating insulin signaling. At hyperglycemic clamp only FS-60 potentiated first phase insulin secretion in diabetic animals; the second phase was not increased. CONCLUSIONS FS-60, a lignan-rich fraction, improves glucose homeostasis by increasing glucose disposal rates and enhancing hepatic insulin sensitivity by working as a PPAR-γ agonist in type-2 diabetic rats.

Capsiate improves glucose metabolism by improving insulin sensitivity better than capsaicin in diabetic rats.

Red peppers and red pepper paste are reported to have anti-obesity, analgesic and anti-inflammatory effects in animals and humans due to the capsaicin in red pepper. We investigated whether consuming capsaicin and capsiate, a nonpungent capsaicin analogue, modifies glucose-stimulated insulin secretion, pancreatic β-cell survival and insulin sensitivity in 90% pancreatectomized (Px) diabetic rats, a moderate and non-obese type 2 diabetic animal model. Px diabetic rats were divided into 3 treatment groups: 1) capsaicin (Px-CPA), 2) capsiate (Px-CPI) or 3) dextrose (Px-CON) and provided high fat diets (40 energy % fat) containing assigned components (0.025% capsaicin, capsiate, or dextrose) for 8 weeks. Both capsaicin and capsiate reduced body weight gain, visceral fat accumulation, serum leptin levels and improved glucose tolerance without modulating energy intake in diabetic rats. In comparison to the control, both capsaicin and capsiate potentiated first and second and phase insulin secretion during hyperglycemic clamp. Both also increased β-cell mass by increasing proliferation and decreasing apoptosis of β-cells by potentiating insulin/IGF-1 signaling. However, only capsiate enhanced hepatic insulin sensitivity during euglycemic hyperinuslinemic clamp. Capsiate reduced hepatic glucose output and increased triglyceride accumulation in the hyperinsulinemic state and capsiate alone significantly increased glycogen storage. This was related to enhanced pAkt→PEPCK and pAMPK signaling. Capsaicin and capsiate reduced triglyceride storage through activating pAMPK. In conclusion, capsaicin and capsiate improve glucose homeostasis but they differently enhance insulin sensitivity in the liver, insulin secretion patterns, and islet morphometry in diabetic rats. Capsiate has better anti-diabetic actions than capsaicin.