• 생약학회지
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• 제37권2호통권145호
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• pp.103-109
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• 2006

Advanced glycation end products (AGEs) formation plays an important role in the progression of diabetic complications. To develop effective herbal formulations with suppression of diabetic nephropathy, a common complication in diabetic patients, we evaluated inhibitory activities of KIOM-79, a new herbal prescription, on the formation of AGEs using in vitro and in vivo model systems. Effects of KIOM-79 on the expression of AGEs, RAGEs (receptor for Advanced glycation end products), type IV collagen and renal $TGF-{\beta}1$ mRNA was also examined in streptozotocon (STZ)-induced diabetic rats. STZ-induced diabetic rats were treated orally with KIOM-79 (250 and $500\;kg^{-1}$ once a day for 13 weeks). In vitro system KIOM-79 suppressed the formation of AGEs $(18.12\;{\mu}g/ml)$. In STZ-induced diabetic rats showing accumulation of AGE and RAGE, pathological examination revealed that KIOM-79 prevented AGE and RAGE deposition in the kidney. In STZ induced diabetic rats, the expansion of mesangial matrix and the glomerular tufts seemed to be larger than those in normal rats. Howεver, after administration with KIOM-79, mesangial metrix and glomerular volume were decreased, and overexpression of type IV collagen was also decreased. Overexpression of renal $TGF-{\beta}1$ mRNA was inhibited significantly. These results suggest that the KIOM-79 might be an effective herbal prescription to prevent or alleviate the progression of diabetic nephropathy.

• Asian-Australasian Journal of Animal Sciences
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• 제23권5호
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• pp.672-679
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• 2010

Diabetes mellitus is a worldwide epidemic with high mortality. As concern over this disease rises, the number and value of research grants awarded by the National Research Foundation of Korea (NRF) have increased. Diabetes mellitus is classified into two groups. Type 1 diabetes requires insulin treatment, whereas type 2 diabetes, which is characterized by insulin resistance, can be treated using a variety of therapeutic approaches. Hyperglycemia is thought to be a primary factor in the onset of diabetes, although hyperlipidemia also plays a role. The major organs active in the regulation of blood glucose are the pancreas, liver, skeletal muscle, adipose tissue, intestine, and kidney. Diabetic complications are generally classified as macrovascular (e.g., stroke and heart disease) or microvascular (i.e., diabetic neuropathy, nephropathy, and retinopathy). Several animal models of diabetes have been used to develop oral therapeutic agents, including sulfonylureas, biguanides, thiazolidinediones, acarbose, and miglitol, for both type 1 and type 2 diseases. This review provides an overview of diabetes mellitus, describes oral therapeutic agents for diabetes and their targets, and discusses new developments in diabetic drug research.

• 대한핵의학회지
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• 제33권4호
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• pp.398-404
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• 1999

목적: 당뇨병성 신증은 말기 신부전증의 가장 흔한 원인으로서 그 빈도가 증가되고 있다. $^{99m}Tc$-DMSA는 신피질용 방사성 의약품으로 개발되었으며 신피질의 기능 손상 유무를 형태적으로 관찰하기가 용이하다. 저자들은 $^{99m}Tc$-DMSA 신섭취율이 당뇨병 환자에서 단백뇨의 정도에 따라 차이가 있는지를 확인하고, 당뇨병성 신증의 조기 예측인자로서 유용한 지를 알아보고자 하였다. 대상 및 방법: 1996년 1월부터 1997년 12월까지 당뇨병으로 본원에 입원한 145명(남자 64, 여자 81, 평균연령 56세)의 환자를 대상으로 $^{99m}Tc$-DMSA 신스캔을 시행하고 신섭취율을 구하였다. 환자를 24시간 소변의 단백배설량에 따라 정상 단백뇨군(1군), 미세단백뇨군(2군), 현성단백뇨군(3군)으로 구분하여 $^{99m}Tc$-DMSA 신섭취율의 차이 및 $^{99m}Tc$-DMSA 신섭취율과 다른 임상지표들과의 관계를 비교, 분석하였다. 결과: $^{99m}Tc$-DMSA 신섭취율은 2군에서 $40.8{\pm}11.0%$로 1군의 $54.4{\pm}6.3%$보다 의미 있게 낮았으며(p<0.001), 3군의 $27.7{\pm}12.0%$보다는 유의하게 높았다(p<0.001). 각 군에서 $^{99m}Tc$-DMSA 신섭취율은 혈청 크레아티닌치와는 유의한 음의 상관이 있었으며(r=-0.62, p<0.001), 크레아티닌 제거율과는 의미 있는 양의 상관관계를 나타내었다(r=0.70, p<0.001). 결론: 미세단백뇨기 당뇨병 환자의 $^{99m}Tc$-DMSA 신섭취율은 정상 단백뇨를 보인 당뇨병 환자에서보다 유의하게 감소되어 있었으며, 현성단백뇨기의 환자보다 유의하게 높은 것으로 관찰되었다. 따라서 $^{99m}Tc$-DMSA 스캔은 당뇨병 환자에서 당뇨병성 신증을 조기에 진단할 수 있는 객관적인 검사방법으로 유용하다고 생각된다.

• 대한의생명과학회지
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• 제10권3호
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• pp.203-210
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• 2004

It has been reported that glomerulosclerosis mediated by the dysfunction of mesangial cells and insulin-like growth factors (IGFs) are associated with the development of diabetic nephropathy. However, it is not yet known the effect of high glucose on IGF-I, -II secretion, IGF-I receptor, and IGFBPs expression in the mesangial cells. Thus, this study was conducted to examine the effect of high glucose on IGF system and its involvement of protein kinase C (PKC) and oxidative stress in mesangial cells. In this study, high glucose (25 mM) increased IGF-I and IGF-II secretion and mRNA expression (P<0.05), which was blocked by PKC inhibitor (staurosporine, 10/sup -8/ M) and antioxidant (N-acetyl cystein, 10/sup -5/ M). High glucose decreased IGFBP-1 and -2 expression but increased IGFBP-5 expression. These alteration of IGFBPs by high glucose was also prevented by staurosporine and NAC, suggesting the role of PKC and oxidative stress. Indeed, high glucose increased PKC activity. Furthermore, high glucose-induced increase of lipid peroxide (LPO) formation was blocked by PKC inhibitors. In conclusion, high glucose alters IGF system via PKC-oxidative pathways in mesangial cells.

• 한국융합학회논문지
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• 제9권10호
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• pp.467-475
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• 2018

본 연구는 당뇨병성 신증 환자들의 자가 관리 연구에서 사용된 측정도구를 고찰함으로써 이후 자가 관리를 사정하기 위한 기초 자료로 이용하고자 시행되었다. 4개의 국외 데이터베이스 이용하였고, 검색용어로는 "Diabetes Mellitus", "Self-care", "Kidney Disease"가 사용되었다. 그 결과 8개의 연구가 선정되었고, 8개의 도구가 연구에서 사용되었다. 그러나 이 도구들은 전반적인 환자 또는 당뇨병 환자, 혈액투석 환자를 대상으로 개발되어, 실제 당뇨병성 신증 환자의 특이성을 지닌 도구는 확인되지 않았다. 따라서 앞으로 당뇨병에서 신장질환으로 이행될 때 변화되는 당뇨병성 신증의 특이성을 고려한 자가 관리를 확인하기 위한 측정도구 개발 연구가 이루어져야 할 것이다.

• 동의생리병리학회지
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• 제21권3호
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• pp.671-678
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• 2007

Diabetes is a disease in which the body does not produce or properly use insulin. Etiological studies of diabetes and its complications showed that oxidative stress might play a major role. Therefore, many efforts have been tried to regulate free oxygen radicals for treating diabetes and its complications. Gamigukihwandong-hwan has been known to be effective for the treatment of diabetes. The present study was carried out to investigate the effect of Gamigukihwandong-hwan on renal function, peroxynitrite (ONOO$^-$) scavenging activity and polyol pathway in streptozotocin-induced diabetic rats. The crushed Gamigukihwandong-hwan was extracted 3 times, each time with 3 volumes of methyl alcohol at 60$^{\circ}C$ for 24 h. The extract was filtered and evaporated under a reduced pressure using a rotary evaporator to yield 74.95 g. Gamigukihwandong-hwan extract was oral-administered 100 mg per 1 kg of body weight for 20 days to the diabetic rats induced by streptozotocin (60 mg/kg). The effects of Gamigukihwandong-hwan extract on the streptozotocin-induced diabetic rats were observed by measuring the serum level of glucose, insulin, lipid components, creatinine and BUN, and also the kidney levels of superoxide anion radical (${\cdot}O_2^-$), nitric oxide (NO) and ONOO$^-$, and also the enzyme activities involved in polyol pathway. The Effects of Gamigukihwandong-hwan on the streptozotocin-induced diabetic rats with regards to body weight, blood glucose and insulin levels, creatinine and BUN levels, total cholesterol and triglyceride levels, and HDL-cholesterol levels were all shown to be good enough to cure and prevent the diabetes and its complications. Gamigukihwandong-hwan inhibited the generation of ${\cdot}O_2^-$, NO and ONOO$^-$ in the kidney of streptozotocin-induced diabetic rats. Renal aldose reductase and sorbitol dehydrogenase activities were increased in the streptozotocin-induced diabetic rats, whereas the ones in the Gamigukihwandong-hwan administered group among the streptozotocin-induced diabetic rats were reversed toward the natural activities. Gamigukihwandong-hwan might inhibit the development of diabetic nephropathy by scavenging reactive oxygen and nitrogen species, thereby by reducing oxidative stresses and also by regulating the activities of polyol pathway enzymes, all of which could help to recover the function of kidney.

• 대한의생명과학회지
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• 제14권1호
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• pp.19-26
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• 2008

This study investigated the effect of Rehmanniae Radix preparata extract on the antioxidant enzymes of kidney and renal function in streptozotocin-induced diabetic rats. Male Sprague-Dawley rats were divided into three groups including normal control (NC), diabetic control (DC), and diabetic treatment with Rehmanniae Radix preparata (DRR). Over a 4-week study period, Rehmanniae Radix preparata aqueous extract was administered orally at 1124 mg/kg BW/day. The serum glucose level in the DRR group was significantly lower (P<0.05) than the DC group. The serum blood urea nitrogen in diabetic groups was significantly higher (P<0.001) than the NC group. The urinary total protein level in the DRR group was significantly lower (P<0.05) than the DC group. The renal xanthine oxidase activity in the DRR group was significantly lower (P<0.01) than the DC group. The renal catalase activity in the DC group was significantly lower (P<0.05) compared to the NC group and that was significantly higher (P<0.05) in the DRR group than the DC group. In conclusion, these results indicated that Rehmanniae Radix preparata can prevent or retard the development of diabetic nephropathy via its beneficial effects for correcting the hyperglycemia and favorable effects on antioxidant enzyme system.

• 생명과학회지
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• 제18권1호
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• pp.23-29
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• 2008

인삼은 고전적으로 항당뇨 효과가 있는 것으로 보고되고 있다. Insulin-like growth factor (IGF) 역시 당뇨병성 신증의 발병 초기에 중요한 역할을 하는 것으로 알려져 있다. 이에 본 연구에서는 mesangial 세포에서 고포도당에 의한 IGF 분비에 대한 ginsenoside의 차단 효과 및 이와 관련된 신호전달계를 알아보았다. 결과는 다음과 같다. 고포도당에 의해 증가 되었던 IGF-I 및 IGF-II 분비 촉진 작용은 GTS, PD 및 PT 처리 시 차단되었으며, 세포 성장 촉진작용에서도 같은 효과를 볼 수 있었다. 아울러 고포도당에 의한 산화성 스트레스 종가, GSH 감소, AA 방출 증가 작용 및 $PGE_2$ 합성 증가 작용은 GTS 처리시 현저하게 차단되었으며 PD 및 PT 처리 시 역시 억제 되는 것으로 나타났다. 이상의 결과를 볼 때 mesangial 세포에서 ginsenoside는 산화성 스트레스 및 arachidonic acid 활성 경로를 억제하여 고포도당에 의한 IGFs 분비 작용을 차단하는 것으로 나타났다.

• 동의생리병리학회지
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• 제31권5호
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• pp.264-269
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• 2017

Prunella vulgaris, well-known traditional medicinal plant, is used for the cure of abscess, scrofula, hypertension and urinary diseases. Diabetic nephropathy is the most common cause of end-stage renal disease. The pathological characteristics of diabetic nephropathy are glomerular and tubular basement membrane thickening. The aim of the present study was to evaluate the effect of Prunella vulgaris, on diabetic glomerular injury in streptozotocin-induced diabetes rats. Diabetes mellitus was induced by a single intraperitoneal injection of streptozotocin (STZ; 45 mg/kg) and confirmed by random glucose level higher than ${\leq}300mg/dL$. The experimental rats were divided into five groups: control group (Male SD rats), STZ group (Male SD rats injected STZ), Aminoguanidine group (Male SD rats injected STZ + AG 100 mg/kg/day), Low dose group (Male SD rats injected STZ + APV 100 mg/kg/day), High dose group (Male SD rats injected STZ + APV 300 mg/kg/day). AG or APVs were administered once a day for 8 weeks. Body weight and food/water intake were measured every four weeks. At the end of study, the kidneys were collected and cut into pieces for immunohistochemistry and western blot analysis. Our study showed that body weight and water/food intake were no significant differences between untreated STZ-induced diabetic rat and APV treated-STZ rat. However, phosphorylation of receptor-regulated Smads (Smad3) was significantly decreased in APV treated-STZ rat as compared with the diabetic group. In addition, APV was improved nephrin level in kidney tissue. Therefore, we suggest that APV has a protective effect against STZ-induced diabetic glomerular injury.

• 대한본초학회지
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• 제23권3호
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• pp.85-91
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• 2008

Objectives : This study aimed to evaluate the anti-diabetic effect of Wen-Pi-Tang-Hab-Wu-Ling-San (WHW) extract in streptozotocin(STZ)-induced type-1 diabetic rats. Methods : Experimental diabetes were induced by intraperitoneal injection of streptozotocin (60 mg/kg). Two groups of STZ-induced diabetic rats were given the following treatments for 2 weeks by oral Administrations : (1) WHW 10 mg/kg, (2) WHW 100 mg/kg. In addition, vehicle-treated diabetic and nondiabetic controls were used in the experiment. The effects of WHW extract on STZ-induced diabetes were observed by measuring the changes of body weights and the levels of fasting blood glucose, insulin, urea nitrogen (BUN) and creatinine level in sera of rats, respectively. Results : In comparison control group, WHW-treated groups (100 mg/kg) were significantly decreased fasting blood glucose levels and increased serum insulin levels in STZ-induced diabetic rats. Moreover, WHW-treated groups (100 mg/kg) were reduced s-creatinie levels in STZ-induced diabetic rats. In addition, the changes related to diabetic nephropathy with body weight were significantly lower in WHW extract-dosing groups than in the diabetic control. Conclusions : The study thus showed that WHW extract enhanced the anti-diabetic effect in STZ-induced diabetic rats by improving the hypoglycemia. It also increased pancreatic insulin content in these rats.