• Asian-Australasian Journal of Animal Sciences
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• v.23 no.5
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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.

• The Korean Journal of Nuclear Medicine
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• v.33 no.4
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• pp.398-404
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• 1999

Purpose: Diabetic nephropathy is the most common cause of end stage renal disease and the incidence is progressively increasing. The aim of this study was to investigate the differences of $^{99m}Tc$-DMSA renal uptake among diabetic patients with normoalbuminuria, microalbuminuria and overt proteinuria, and then to determine the clinical usefulness of $^{99m}Tc$-DMSA in predicting early diabetic nephropathy Materials and Methods: $^{99m}Tc$-DMSA scan was performed and a total renal uptake of $^{99m}Tc$-DMSA was measured in 145 diabetic patients. Patients were divided into 3 groups according to the amount of 24 hour urinary albumin excretion as Group I (normoalbuminuria, 74 cases), Group II (microalbuminuria, 39 cases), and Group III (overt proteinuria, 32 cases). The differences of $^{99m}Tc$-DMSA renal uptake among the 3 groups and the correlation between the renal uptake of $^{99m}Tc$-DMSA and other clinical parameters were analyzed. Results: The total renal uptake of $^{99m}Tc$-DMSA of Group II ($40.8{\pm}11.0%$) was significantly lower than that of Group I ($54.4{\pm}6.3%$, p<0.001). The uptake of Group III ($27.7{\pm}12.0%$) was significantly lower than those of both Group I and Group II (p<0.001). $^{99m}Tc$-DMSA total renal uptakes correlated negatively with serum creatinine level (r=-0.629, p<0.001) and positively correlated with creatinine clearance rate (r=0.102, p<0.001). Conclusion: $^{99m}Tc$-DMSA total renal uptake of diabetic patients with microalbuminuria was significantly decreased compared with that of patients of normoalbuminuria. Therefore, $^{99m}Tc$-DMSA scan can be used as a diagnostic study for early detection of the diabetic nephropathy.

• Biomedical Science Letters
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• v.10 no.3
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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.

• Journal of the Korea Convergence Society
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• v.9 no.10
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• pp.467-475
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• 2018

The purpose of this study was to describe self-management related to diabetic nephropathy(DN) patients and analyze instrument for measurement of self-management. Literature search was conducted using computerized databases such as Pubmed, CINAHL, Embase, and Cochrane. The search term of this study were "Diabetes Mellitus", "Self-care", "Kidney Disease". A total of 8 articles were collected and 8 measurement instruments used in the study. But, included studies were assessing the self-management for DN using non-DN specific instruments. Thus, DN specific instrument for measuring the self-care should be developed in future study.

• Journal of Physiology & Pathology in Korean Medicine
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• v.21 no.3
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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.

• Biomedical Science Letters
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• v.14 no.1
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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.

• Journal of Life Science
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• v.18 no.1
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• pp.23-29
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• 2008

Panax ginseng C. A. MEYER is one of the most widely used herbal medicines in the Asian countries and has diverse functions including anti-diabetic action. The dysfunctions of mesangial cells in hyperglycemic conditions are implicated in the development of diabetic nephropathy. Insulin-like growth factors (IGFs) are also associated with the onset of diabetic nephropathy. Thus, we examined the effect of ginsenosides against high glucose-induced dysfunction of primary cultured rat mesangial cells. In the present study, high glucose increased IGF-I and IGF-II secretion in mesangial cells. Ginsenoside total saponin (GTS) prevented high glucose-induced increase of IGF-I and IGF-II secretion in mesangial cells. In addition, GTS prevented high glucose-induced increase of lipid peroxide formation and decrease of GSH contents. GTS also ameliorates high glucose-induced increase of arachidonic acid release and decrease of prostaglandin $E_2$. In conclusion, GTS prevented high glucose-induced dysfunction of mesangial cells via inhibition of oxidative stress and arachidonic acid pathways.

• Journal of Physiology & Pathology in Korean Medicine
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• v.31 no.5
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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.

• The Korea Journal of Herbology
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• v.23 no.3
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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.

• Experimental and Molecular Medicine
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• v.51 no.2
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• pp.9.1-9.10
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• 2019

Mesangial cell proliferation has been identified as a major factor contributing to glomerulosclerosis, which is a typical symptom of diabetic nephropathy (DN). Lysophosphatidic acid (LPA) levels are increased in the glomerulus of the kidney in diabetic mice. LPA is a critical regulator that induces mesangial cell proliferation; however, its effect and molecular mechanisms remain unknown. The proportion of ${\alpha}-SMA^+/PCNA^+$ cells was increased in the kidney cortex of db/db mice compared with control mice. Treatment with LPA concomitantly increased the proliferation of mouse mesangial cells (SV40 MES13) and the expression of cyclin D1 and CDK4. On the other hand, the expression of $p27^{Kip1}$ was decreased. The expression of $Kr{\ddot{u}}ppel$-like factor 5 (KLF5) was upregulated in the kidney cortex of db/db mice and LPA-treated SV40 MES13 cells. RNAi-mediated silencing of KLF5 reversed these effects and inhibited the proliferation of LPA-treated cells. Mitogen-activated protein kinases (MAPKs) were activated, and the expression of early growth response 1 (Egr1) was subsequently increased in LPA-treated SV40 MES13 cells and the kidney cortex of db/db mice. Moreover, LPA significantly increased the activity of the Ras-related C3 botulinum toxin substrate (Rac1) GTPase in SV40 MES13 cells, and the dominant-negative form of Rac1 partially inhibited the phosphorylation of p38 and upregulation of Egr1 and KLF5 induced by LPA. LPA-induced hyperproliferation was attenuated by the inhibition of Rac1 activity. Based on these results, the Rac1/MAPK/KLF5 signaling pathway was one of the mechanisms by which LPA induced mesangial cell proliferation in DN models.