• KSBB Journal
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• v.21 no.6 s.101
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• pp.466-473
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• 2006

Impaired insulin secretion from pancreatic beta-cells in response to glucose is an important feature in the pathology of non-insulin-dependent diabetes mellitus (NIDDM). In the course of screening for useful insulin secretagogues, we have isolated and identified YHB-2017 (Genistein) as a insulin secretion potentiator from fermentation broths of our in-house microbial library. The insulinotropic activity of YHB-2017 in isolated rat pancreatic islets was exerted only at high concentration of glucose (8.3-16 mM) but not at low concentration of glucose (3.3-5.5 mM). Also, in perifusion study with isolated rat pancreatic islets, YHB-2017 stimulated insulin secretion in a time-dependent manner when YHB-2017 was added to KRB buffer containing 16 mM glucose. In the presence of $200\;{\mu}M$ diazoxide and 35 mM KCI, which stimulates maximum $Ca^{2+}$ influx independently of KATP channel, YHB-2017 enhanced KATP channel-independent insulin secretion at high concentration glucose (16 mM). To elucidate the mechanisms of the glucose-dependent potentiation effect of YHB-2017, pharmacologic inhibitors for protein kinase A, protein kinase C and calcium/calmodulin kinase II were pre-treated and then the potentiation effect of YHB-2017 on insulin secretion was investigated. Pre-treatment of H89 as a PKA inhibitor had a significant inhibitory effect on YHB-2017-induced potentiation effect. Furthermore, western immunoblotting analyses revealed that YHB-2017 increased phosphorylation of PKA substrates and cAMP response element-binding protein (CREB) under high concentration of glucose. These results demonstrated that the insulinotropic effect of YHB-2017 is mediated through PKA signal pathway and activated amplifying $K_{ATP}$ channel-independent insulin secretion pathway.

• Journal of Life Science
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• v.16 no.5
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• pp.767-772
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• 2006

This study was to investigate the effect of betaine on the hypoglycemia and hepatoprotection of streptozotocin(STZ)-induced diabetic rats. Male Sprague-Dawley rats weighing around 280 g were randomly assigned to the three experimental groups: a healthy normal group and two groups with STZ-induced diabetes and fed either control diet or betaine diet. Betaine given to the STZ-diabetic rats had significant effect in lowering the serum glucose concentrations compared to the STZ-diabetic rats. The alanine aminotransferase (AST) and aspartate aminotransferase (ALT) activities and triglyceride contents in serum were dramatically higher in the STZ-diabetic rats, but these increases in relation to diabetes also decreased in the STZ-diabetic rats fed betaine. However, the total-cholesterol concentration in the STZ-diabetic rats was even increased by betaine. The morphology of the pancreatic islets in the normal rats showed a typical round form, but most of the islets in the STZ-diabetic rats showed severe morphological alterations by being markedly destroyed. However, the islet morphology of STZ-diabetic rats given betaine mostly maintained a normal rounded appearance. The present study strongly suggests that the administration of betaine showed a moderate hypoglycemic effect by protecting the pancreatic beta-cells by morphological examination from STZ-induced destruction.

• Journal of Nutrition and Health
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• v.47 no.6
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• pp.394-402
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• 2014

Purpose: Dendropanax morifera Leveille (DML) exhibits diverse biological and pharmacological activities, including anti-oxidative effect, anti-cancer activity, hepatoprotection, immunological stimulation, and bone regeneration. As part of the identification for novel functions of DML, we investigated the therapeutic effects of DML on diabetes induced by streptozotocine (STZ) treatment. Methods: First, the four extracts including the water extract of leaf (DLW), the ethanol extract of leaf (DLE), the water extract of stem (DSW), and the ethanol extract of stem (DSE) were collected from the leaf and stem of DML using a hot water and ethanol solvent. Alterations in body weight, glucose concentration, insulin level, and pancreatic islet structure were investigated in diabetic mice after treatment with extracts of DML for 2 weeks. Results: Among four extracts, the highest level of total polyphenols and total flavonoids was detected in DLW, while the lowest level of these was measured in DSE. The radical scavenging activity was also higher in DLW than in the other three extracts at the concentration of $25-100{\mu}g/mL$, although this activity was maintained at a constant level in all groups at the concentration of $500{\mu}g/mL$. Based on the results of anti-oxidant activity, DLW and DLE were selected for examination of anti-diabetic effects in a diabetes model. Body weight was gradually decreased in all STZ treated groups compared with the No treated group. However, four STZ/DML treated groups maintained a high level of body weight during 7-14 days, while the STZ/vehicle treated group showed a gradual decrease of body weight during the same period. Also, a significant decrease or increase in the concentration of glucose and insulin in the blood of the diabetes model was detected in a subset of groups, although the highest increase was detected in the STZ/DLE-200 treated group. In addition, the histological structure of pancreatic islet was significantly recovered after treatment with DLW and DLE. Conclusion: These results suggest that DLW and DLE may contribute to attenuation of clinical symptoms of diabetes as well as prevent the destruction of pancreatic ${\beta}$-cells in STZ-induced diabetes mice.

• Journal of Acupuncture Research
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• v.25 no.2
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• pp.91-103
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• 2008

목적 : 중완과 족삼리 자침이 neonatal-streptozotocin 모델 실험동물에서 혈당과 베타세포 손상에 대한 보호효과를 알아보고자 하였다. 방법 : 비-비만 제2형 당뇨모델인 neonatal STZ 실험동물을 무처치 대조군, 임의혈 대조군, 중완 자침군, 족삼리 자침군으로 나누어 90일 동안 실험하였다. 체중과 혈당을 3일에 한 번씩 측정하였으며, 90일이 경과 후 혈중 인슐린을 측정하고 당부하 검사를 실시한 후 동물을 희생시켜 이자 조직을 적출하고 표본을 제작하였다. 면역세포화학법을 통하여 이자의 베타세포 손상에 대한 세포보호효과를 관찰하였다. 결과 : 중완 자침군과 족삼리 자침군은 대조군에 비해 유의한 혈당 강하 효과가 관찰되었다. 인슐린 농도는 모든 군에서 상승하였으며 당부하 검사에서는 임의혈 자침군과 중완 자침군 및 족삼리 자침군에서 내당능이 있는 것으로 나타났다. 조직 검사에서는 무처치 대조군과 임의혈 대조군에서는 베타세포 손상이 심했으나, 중완 자침군과 족삼리 자침군에서는 베타세포 손상에 대한 세포보호 효과가 현저하게 관찰되었다. 결론 : 중완과 족삼리 자침은 비-비만 제2형 당뇨모델에서 손상된 베타세포를 회복하고 인슐린 분비를 촉진하여 혈당을 강하시키는 효과가 있는 것으로 사료된다.

• Clinical and Experimental Pediatrics
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• v.61 no.7
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• pp.217-220
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• 2018

Purpose: Type 1 diabetes mellitus (T1DM) is a chronic and immune-mediated disease, which is characterized by the progressive destruction of pancreatic beta cells. T1DM precipitates in genetically susceptible individuals through environmental factors. In this study, we aimed to evaluate the impact of autoimmunity and intestinal colonization of Candida albicans on the development of T1DM. Methods: Forty-two patients newly diagnosed with T1DM and 42 healthy subjects were included in this monocentric study. The basic and clinical characteristics of the patients were recorded. T1DM-, thyroid-, and celiac-associated antibodies were evaluated. Stool cultures for C. albicans were performed to assess whether or not gut integrity was impaired in patients with T1DM. Results: The evaluation of T1DM- and thyroid-associated antibodies showed that the prevalences of islet cell antibodies and antithyroperoxidase positivity were higher in the study patients than in the patients in the control group. Furthermore, the direct examination and culture of fresh stool samples revealed that 50% of the patients with T1DM and 23.8% of the control subjects had fungi (C. albicans). Conclusion: Through this study, we suggest that the presence of intestinal C. albicans colonization at the time of the diagnosis of T1DM may indicate impairment of normal intestinal microbiota. We also suggest that there may be a tendency of T1DM in patients with a high prevalence of intestinal C. albicans.

• Nutrition Research and Practice
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• v.7 no.2
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• pp.103-108
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• 2013

A folk prescription consisting of Alnus hirsuta, Rosa davurica, Acanthopanax senticosus and Panax schinseng has been used in the treatment of diabetes mellitus. The aim of the present investigation was to evaluate the antidiabetic effects of the herb formula extract (HFE) composed of Alnus hirsuta, Rosa davurica, Acanthopanax senticosus and Panax schinseng in the streptozotocin (STZ)-induced diabetic rats. The HFE was mixed in the food supply of the healthy and STZ-induced diabetic male Sprague-Dawley rats, and its effects on the body weight, water and food intake, hyperglycemia, hypolipidemic and islet structure were studied. The treatment of the rats with STZ for 6 weeks resulted in marasmus, polydipsia, polyphagia, hyperglycemia and hypoinsulinemia. In addition, the diabetic rats showed an apparent decrease in the insulin immunoreactivity and the number of ${\beta}$-cells in the pancreas. The addition of the HFE to the rats' food supply significantly lowered the serum glucose and the serum triglycerides level and preserved the normal histological appearance of the pancreatic islets. These results indicate that the HEF have a strong antidiabetic potential along with the significant hypoglycemic and hypolipidemic effects, which may be applicable in the pharmaceutical industry.

• Korean Journal of Pharmacognosy
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• v.33 no.1 s.128
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• pp.21-28
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• 2002

Antidiabetic effects of the acid hydrolysate of silk fibroin were investigated by oral administration to animal models for diabetes mellitus, Fibroin protein was extracted from cocoon and digested to peptides of low-molecular weight range (mainly below 3,000) and amino acids by acid hydrolysis, Feeding of the fibroin hydrolysate resulted in a significant recovering effect on reduction of body weight gain and a lowering effect on blood glucose gain in streptozotocin-induced diabetic Sprague Dawley rats (STZ rats) which were used as an insulin-dependent diabetic animal model. But the body weight and blood glucose level in C57BL/KsJ-db/db mice (db/db mice), an non-insulin-dependent diabetic animal model, were not changed significantly by the feeding, On the other hand, plasma leptin levels increased according to increased feeding amount of the hydrolysate in STZ rats and db/db mice in common, It was concluded from the results that the fibroin hydrolysate might stimulate the insulin secretion by recovering or activating pancreatic ${\beta}$ cells and result in the increased plasma leptin level. It was also deduced that the antidiabetic improvements in body weight and blood glucose gain in STZ were thought to be due to the increased insulin secretion, but in db/db mice of which the diabetic symptoms were caused by insulin resistance, the stimulated secretion of insulin was unlikely to be able to change body weight and blood glucose level significantly.

• CELLMED
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• v.4 no.4
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• pp.27.1-27.5
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• 2014

Picrorhiza kurroa Royle ex Benth. (Scrophulariaceae) is a traditional Ayurvedic herb known as Kutki. It is used as a remedy for diabetes by tribes of North Eastern Himalayan region of India. Present study was conducted to explore the mechanism of antidiabetic activity of standardized aqueous extract of Picrorhiza kurroa (PkE). PkE (100 and 200 mg/kg/day) was orally administered to streptozotocin induced diabetic rats, for 14 consecutive days. Plasma insulin levels were measured and pancreas of rat was subjected to histopathological investigations. Glucose transporter type 4 (GLUT-4) protein content in the total membrane fractions of soleus muscle was estimated by Western blot analysis. Plasma insulin level was significantly increased along with concomitant increase in GLUT-4 content of total membrane fractions of soleus muscle of diabetic rats treated with extract. There was evidence of regeneration of ${\beta}$-cells of pancreatic islets of PkE treated group in histopathological examinations. PkE increased the insulin-mediated translocation of GLUT-4 from cytosol to plasma membrane or increased GLUT-4 expression, which in turn facilitated glucose uptake by skeletal muscles in diabetic rats.

• Journal of Pharmacopuncture
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• v.20 no.4
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• pp.235-242
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• 2017

Irisin is a novel hormone like polypeptide that is cleaved and secreted by an unknown protease from fibronectin type III domain-containing protein 5 (FNDC5), a membrane-spanning protein and which is highly expressed in skeletal muscle, heart, adipose tissue, and liver. Since its discovery in 2012, it has been the subject of many researches due to its potent physiological role. It is believed that understanding irisin's function may be the key to comprehend many diseases and their development. Irisin is a myokine that leads to increased energy expenditure by stimulating the 'browning' of white adipose tissue. In the first description of this hormone, increased levels of circulating irisin, which is cleaved from its precursor fibronectin type III domain-containing protein 5, were associated with improved glucose homeostasis by reducing insulin resistance. Irisin is a powerful messenger, sending the signal to determine the function of specific cells, like skeletal muscle, liver, pancreas, heart, fat and the brain. The action of irisin on different targeted tissues or organs in human being has revealed its physiological functions for promoting health or executing the regulation of variety of metabolic diseases. Numerous studies focus on the association of irisin with metabolic diseases which has gained great interest as a potential new target to combat type 2 diabetes mellitus and insulin resistance. Irisin is found to improve insulin resistance and type 2 diabetes by increasing sensitization of the insulin receptor in skeletal muscle and heart by improving hepatic glucose and lipid metabolism, promoting pancreatic ${\beta}$ cell functions, and transforming white adipose tissue to brown adipose tissue. This review is a thoughtful attempt to summarize the current knowledge of irisin and its effective role in mediating metabolic dysfunctions in insulin resistance and type 2 diabetes mellitus.

• YAKHAK HOEJI
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• v.50 no.6
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• pp.345-350
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• 2006

The pharmacological properties of ginseng are mainly attributed to ginsenosides, the active constituents that are found in the extracts of different species of ginseng. Lately; the studies on ginsenosides are mainly focused on IH-901, a major intestinal bacterial metabolite of ginsenosides. In this study; we examined the anti-diabetic activity of IH-901 in C57BU61 db/db mice model. IH-901 was administrated orally at a dose of 20 mg/kg for 5 weeks. During the experimental period, body weight and blood glucose levels were measured every week. After 5 weeks, db/db mice were sacrificed and diabetic parameters were analyzed. IH-901 treated group showed a significant decrease in fasting blood glucose levels (from 10.5 mM to 9.4 mM), insulin resistance index (from 163.6 to 100.2) and triglyceride levels (from 115.3 to 70.1) compared to the diabetic control. In Pancreatic islets morphology; IH-901 treated group revealed much less infltrated mononuclear cells, indicating that IH-901 recovered ${\beta}$-cell damage due to hyperglycemia. In addition, IH-901 upregulated expressions of glucose transporter 4 (GLUT4) and PPAR-${\gamma}$ in skeletal muscle and adipose tissue, respectively. Taken together IH-901might be a potential anti-hyperglycemic agent with insulin sensitizing effect.