• 대한한방내과학회지
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• 제25권2호
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• pp.277-287
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• 2004

Objective : 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 playa major role. Therefore, many efforts have been made to regulate oxygen free radicals for treating diabetes and its complications. Because Jindangwon has been known to be effective in treatment of diabetes, the methanol extract of Jindangwon was tested for its effectiveness in reducing the oxidative stress induced by Streptozotocin. Methods : Jindangwon was washed, dried in the shade and crushed. The crushed Jindangwon was extracted 3 times, each time with 3 volumes of methyl alcohol at $60^{\circ}C$ for 24 hours. The extract was filtered and evaporated under reduced pressure using a rotary evaporator to yield 30.6 g. Jindangwon extract was oral-administered to the diabetic rats induced by streptozotocin 50 mg per 1 kg of body weight for 15 days. The efficacy of the Jindangwon extract was examined with regard to the enzymatic pathways involved in the oxygen free radical production and the glutathione balance. Results : he effects of the methanol extract of Jindangwon in streptozotocin-induced diabetics rats with regard to body weight, blood glucose level, hepatic lipid peroxide level, hepatic xanthine oxidase activity and type conversion rate, hepatic glutathione level, hepatic glutathione peroxidase activity, hepatic glutathione reductase activity, hepatic aldose reductase activity, and hepatic sorbitol dehydrogenase activity were favorable enough to suggest that it is a cure for diabetes and its complications. Conclusions :These results support Jindangwon as an effective reducing agent for oxidative stress in the tissues and organs by regulating the production of oxygen free radicals. Jindangwon, in particular, shows promising results for its use as a cure, or preventative medicine for diabetes and its complications by reducing oxidative stress in beta-cells of the pancreas.

• 대한한의학회지
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• 제27권1호
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• pp.91-103
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• 2006

Objectives : Etiological studies of diabetes and its complications showed that oxidative stress might play a major role. Therefore, many effects have been fried to regulate oxygen free radicals for treating diabetes and its complications. Because Holotrichia has been known to be effective for the treatment of diabetes, the methanol extract of Holotrichia was tested for its effectiveness in reducing the oxidative stress induced by streptozotocin. Methods : Holotrichia was washed, dried in the shade and crushed. The crushed Holotrichia was extracted 3 times, each time with 3 volumes of methyl alcohol at $60^{\circ}C$ for 24h. The extract was filtered and evaporated under a reduced pressure using a rotary evaporator to yield 17 g. Holotrichia extract was oral-administed to the diabetic rats induced by streptozotocin 50 mg per 1 kg of body weight for 20 days. The efficacy of the Holotrichia extract was examined with regard to the enzymatic pathways involved in the oxygen free radical production and the glutathione balance. Results : The Effects of the methanol extract of Holotrichia in streptozotocin-induced diabolic rats with regards to body weight, blood glucose level, hepatic lipid peroxide level, hepatic superoxide anion radical content. hepatic xanthine oxidase activity and type conversion rate, hepatic glutathione level, hepatic aldose reductase activity, and hepatic sorbitol dehydrogenase activity were shown to be good enough to cure and prevent the diabetes and its complications. Conclusions : These results indicated that Holotrichia might reduce the oxidative stress in the tissues and organs by regulating the production of oxygen free radicals. Especially, Holotrichia might prevent and cure the diabetes and its complications by reducing the oxidative stress in the ${\beta}$-cells of pancreas. Some suggestions on biophoton experiments were made.

• Molecules and Cells
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• 제45권4호
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• pp.180-192
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• 2022

Nuclear receptor coactivator 6 (NCOA6) is a transcriptional coactivator of nuclear receptors and other transcription factors. A general Ncoa6 knockout mouse was previously shown to be embryonic lethal, but we here generated liver-specific Ncoa6 knockout (Ncoa6 LKO) mice to investigate the metabolic function of NCOA6 in the liver. These Ncoa6 LKO mice exhibited similar blood glucose and insulin levels to wild type but showed improvements in glucose tolerance, insulin sensitivity, and pyruvate tolerance. The decrease in glucose production from pyruvate in these LKO mice was consistent with the abrogation of the fasting-stimulated induction of gluconeogenic genes, phosphoenolpyruvate carboxykinase 1 (Pck1) and glucose-6-phosphatase (G6pc). The forskolin-stimulated inductions of Pck1 and G6pc were also dramatically reduced in primary hepatocytes isolated from Ncoa6 LKO mice, whereas the expression levels of other gluconeogenic gene regulators, including cAMP response element binding protein (Creb), forkhead box protein O1 and peroxisome proliferator-activated receptor γ coactivator 1α, were unaltered in the LKO mouse livers. CREB phosphorylation via fasting or forskolin stimulation was normal in the livers and primary hepatocytes of the LKO mice. Notably, it was observed that CREB interacts with NCOA6. The transcriptional activity of CREB was found to be enhanced by NCOA6 in the context of Pck1 and G6pc promoters. NCOA6-dependent augmentation was abolished in cAMP response element (CRE) mutant promoters of the Pck1 and G6pc genes. Our present results suggest that NCOA6 regulates hepatic gluconeogenesis by modulating glucagon/cAMP-dependent gluconeogenic gene transcription through an interaction with CREB.

• 대한한방내과학회지
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• 제27권4호
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• pp.811-821
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• 2006

Objectives : 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 methods have been tried to regulate oxygen free radicals for treating diabetes and its complications. Because Mori foliumhas been known to be effective for the treatment of diabetes, the methanol extract of Mori folium was tested for its effectiveness in reducing the oxidative stress induced by streptozotocin. Methods : The crushed Mori folium was extracted 3 times, each time with 3 volumes of methyl alcohol at $60^{\circ}C$ or 24 h. The extract was filtered and evaporated under reduced pressure using a rotary evaporator to yield 11.7 g. Mori folium extract was oral-administered to diabetic rats induced by streptozotocin at 100 mg per 1 kg of body weight for 20 days. The efficacy of the Mori foliumextract was examined with regard to the enzymatic pathways involved in oxygen free radical production and glutathione balance. Results : The effects of the Mori foliumin streptozotocin-induced diabetic rats with regards to body weight, blood glucose and insulin level, hepatic lipid peroxide level, hepatic glutathione level, hepatic glutathione S-transferase and glutathione peroxidase level, hepatic aldose reductase activity, and hepatic sorbitol dehydrogenase activity were shown to be good enough to cure and prevent diabetes and its complications. Conclusions : These results indicated that Mori folium might reduce oxidative stress in tissues and organs by regulating the production of oxygen free radicals. Especially Mori folium might prevent and cure diabetes and its complications by reducing oxidative stress in the ${\beta}-cells$ of the pancreas.

• The Korean Journal of Physiology and Pharmacology
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• 제3권6호
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• pp.571-578
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• 1999

This study evaluated the effects of PKC activation using phorbol 12-myristate 13-acetate (PMA) and PKC inhibition using the isoquinoline sulfomide derivative H-7 on hemodynamics and glucoregulation in the isolated perfused rat liver. Livers were isolated from fed male Holtzman rats and perfused with Krebs Ringer bicarbonate solution under a constant flow of 50 ml/min at $35^{\circ}C.$ Portal vein pressure, glucose and lactate concentrations in the medium and oxygen consumption rates were continuously monitored by a Grass polygraph, YSI glucose and lactate monitors, and a YSI oxygen monitor, respectively. PMA at concentration of 2 to 200 nM increased the portal vein pressure, glucose and lactate production, but decreased oxygen consumption rate in a dose-dependent fashion. H-7 $(200\;{\mu}M)$ attenuated PMA (50 nM)-induced vasoconstriction $(15.1{\pm}1.36\;vs\;10.56{\pm}1.17\;mmHg),$ glucose production rate $(91.3{\pm}6.15\;vs\;71.8{\pm}2.50\;{\mu}moles/g/hr),$ lactate production rate $(72.4{\pm}6.82\;vs\;53.6{\pm}4.82\;{\mu}moles/g/hr)$ and oxygen consumption rate $(33.7{\pm}1.41\;vs\;27.9{\pm}1.75\;{\mu}l/g/min).$ The effects of PMA were blocked either by addition of verapamil $(9\;{\mu}M)$ or perfusion with $Ca^{2+}-free$ KRB. These results suggest that the hemodynamic and glucoregulatory changes in the perfused rat liver are mediated by protein kinase C activation and require $Ca^{2+}$ influx from the extracellular fluid.

• BMB Reports
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• 제49권3호
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• pp.139-148
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• 2016

In the past decade, the incidence of type 2 diabetes (T2D) has rapidly increased, along with the associated cardiovascular complications. Therefore, understanding the pathophysiology underlying T2D, the associated complications and the impact of therapeutics on the T2D development has critical importance for current and future therapeutics. The prevailing feature of T2D is hyperglycemia due to excessive hepatic glucose production, insulin resistance, and insufficient secretion of insulin by the pancreas. These contribute to increased fatty acid influx into the liver and muscle causing accumulation of lipid metabolites. These lipid metabolites cause dyslipidemia and non-alcoholic fatty liver disease, which ultimately contributes to the increased cardiovascular risk in T2D. Therefore, understanding the mechanisms of hepatic insulin resistance and the specific role of liver lipids is critical in selecting and designing the most effective therapeutics for T2D and the associated co-morbidities, including dyslipidemia and cardiovascular disease. Herein, we review the effects and molecular mechanisms of conventional anti-hyperglycemic and lipid-lowering drugs on glucose and lipid metabolism.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 1998년도 춘계학술대회
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• pp.1-4
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• 1998

Impaired insulin action in Type 2 diabetes is thought to lead to hyperglycemia, with both environmental and complex genetic factors playing key roles. Although the primary lesion in Type 2 diabetes is unknown, a number of studies suggest that metabolic defects in the liver, skeletal muscle and fat, and pancreatic ${\beta}$-cells contribute to the disease. These metabolic abnormalities are characterized by the overproduction of hepatic glucose, impaired insulin secretion, and peripheral insulin resistance. In current pharmacological treatment of Type 2 diabetes, sulfonylurea (SU) drugs have mainly been used as oral hypoglycemic drugs to stimulate endogenous insulin secretion from ${\beta}$ cells. SU drugs, however, sometimes aggravate the disease by causing fatigue of the pancreatic ${\beta}$ cells, which leads to reduced drug efficacy after long-term treatment. This class of drugs also leads to enhanced obesity arising from the stimulation of endogenous insulin secretion in obese Type 2 diabetic patients, plus an increased incidence of SU-induced hypoglycemia. Since 1980, a major challenge has been made by us to develop a potential pharmacological therapy for the treatment of insulin resistance in peripheral tissues and/or suppression of abnormal hepatic glucose production in Type 2 diabetic patients. Such a drug would be expected to have fewer side effects and retain long-term efficacy.

• The Korean Journal of Physiology and Pharmacology
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• 제28권1호
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• pp.31-38
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• 2024

As in type 1 diabetes, the loss of pancreatic β-cells leads to insulin deficiency and the subsequent development of hyperglycemia. Exercise has been proposed as a viable remedy for hyperglycemia. Lithium, which has been used as a treatment for bipolar disorder, has also been shown to improve glucose homeostasis under the conditions of obesity and type 2 diabetes by enhancing the effects of exercise on the skeletal muscles. In this study, we demonstrated that unlike in obesity and type 2 diabetic conditions, under the condition of insulin-deficient type 1 diabetes, lithium administration attenuated pancreatic a-cell mass without altering insulin-secreting β-cell mass, implying a selective impact on glucagon production. Additionally, we also documented that lithium downregulated the hepatic gluconeogenic program by decreasing G6Pase protein levels and upregulating AMPK activity. These findings suggest that lithium's effect on glucose metabolism in type 1 diabetes is mediated through a different mechanism than those associated with exercise-induced metabolic changes in the muscle. Therefore, our research presents the novel therapeutic potential of lithium in the treatment of type 1 diabetes, which can be utilized along with insulin and independently of exercise.

• Food Science and Biotechnology
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• 제17권6호
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• pp.1228-1234
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• 2008

Having idea to develop more effective anti-diabetic agent from ginseng root, we comprehensively assessed the anti-diabetic activity and mechanisms of ginsam in C57BL/KsJ db/db mice. The db/db mice were divided into 4 groups; diabetic control (DC), ginsam at a dose of 300 or 500 mg/kg (GS300 or GS500) and metformin at a dose of 300 mg/kg (MT300). Ginsam was orally administered for 8 weeks. GS500 reduced the blood glucose concentration and significantly decreased an insulin resistance index. In addition, GS500 reduced the plasma non-esterified fatty acid, triglyceride, and increased high density lipoprotein-cholesterol as well as decreased the hepatic cholesterol and triglyceride. More interestingly, ginsam increased the plasma adiponectin level by 17% compared to diabetic control group. Microarray, quantitative-polymerase chain reaction and enzyme activity results showed that gene and protein expressions associated with glycolysis, gluconeogenesis, and fatty acid oxidation were changed to the way of reducing hepatic glucose production, insulin resistance and enhancing fatty acid $\beta$-oxidation. Ginsam also increased the phosphorylation of AMP-activated protein kinase and glucose transporter expressions in the liver and skeletal muscle, respectively. These changes in gene expression were considered to be the mechanism by which the ginsam exerted the anti-diabetic and anti-dyslipidemic activities in C57BL/KsJ db/db mice.

• Journal of Yeungnam Medical Science
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• 제12권2호
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• pp.269-281
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• 1995

포도당 중합체 투여로 유도한 고혈당 및 고인슐린 혈증이 인슐린 저항성의 발생에 미치는 영향을 규명하기 위하여 hyperinsulinemic euglycemic clamp 기법으로 측정한 당제거율, 당주입율 및 간의 당생성율과 방사성동위원소를 이용한 골격근의 당원질합성능을 측정한 본 연구결과를 요약하면 다음과 같다. Hyperinsulinemic euglycemic clamp 기법으로 평형상태에서 측정한 당제거율은 포도당 중합체군에서 혈중 인슐린의 생리적 및 최대농도 모두에서 정상대조군에 비해서 감소하였으며(p<0.05) STZ 당뇨군에서도 최대인슐린 농도에서 감소하였다(p<0.05). 당 주입율은 생리적 인슐린 농도에서 포도당 중합체군에서 감소하는 경향을 보였으나 최대인슐린 농도에서는 포도당 중합체군과 STZ 당뇨군에서 다같이 유의한 감소를 보였다(p<0.05). 간의 당생성율은 포도당 중합체군에서 생리적 및 최대인슐린 농도에서 다같이 감소하는 경향이었으며, 최대농도군에서는 유의하게 감소(p<0.05)하였다. STZ 당뇨군에서는 최대인슐린 농도에서 정상대조군 및 포도당 중합체군보다 증가하였다(p<0.05). 골격근과 간의 당원질 합성능은 포도당 중합체군이 정상 대조군과 차이가 없었으나 STZ 당뇨군에서는 감소하였다(p<0.05). 이상의 결과로 볼때 포도당 중합체투여로 유도한 고혈당 및 고인슐린증시 말초조직의 인슐린 저항성이 유발되었으나 soleus근과 간의 당원 합성은 장애가 없어서 STZ 당뇨군과 차이를 나타내었다.