• 한국식품과학회지
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• 제33권5호
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• pp.619-625
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• 2001

현재까지 인슐린의 작용력을 향상시키는 약으로 시판되고 있는 것은 thiazolidinediones이 있고 그외에도 몇가지 종류의 물질에 대해서 그 효과를 조사하고 있다. 본 연구에서는 당뇨병의 치료에 효과가 있다고 알려진 한약재로부터 추출한 POD의 인슐린 저항성에 미치는 영향을 조사하였다. 체중이 $338{\pm}35\;$ 인 Sprague Dawley 백서를 두군으로 나누어 한군은 sham 수술을 하여 정상군으로, 다른 한군은 90% 췌장 적제술을 하여 당뇨군(Px)으로 정하였다. Px 백서는 90% 췌장제거 수술을 한 후 2 주동안 혈당을 측정하여 공복 혈당이 9.4 mmol/L이상인 백서를 선택하였다. Sham 백서와 당뇨 백서는 다시 각각 2군으로 나누어 한군은(n=10) 하루에 POD을 0.3 g/kg 체중의 용량으로 식이에 섞어 공급하였고, 다른 한군은(n=10) 위약(P)을 8 주 동안 투여하였다. 식이는 40%지방 식이를 자유롭게 섭취하도록 하였다. 7 주 째 되었을 때 인슐린 저항성을 측정하기 위해 경동맥과 경정맥에 도관을 삽입하였고, 8주째에 $15{\sim}18$시간 금식후 EH clamp 실험을 실시하였다. POD와 P를 투여하기 전에 Px 백서의 혈당은 $9.9{\pm}0.6\;mmol/L$이었고, 정상군의 혈당은 $6.4{\pm}0.5\;mmol/L$이었다. EH clamp를 할 때 체중은 Px 백서에 비해 Sham백서에서 높았으며, 혈당은 POD 투여와 당뇨에 의한 차이가 있었다. Px 백서가 Sham 백서에 비해 기초 인슐린 농도가 낮았고, Sham 백서에서는 POD군이 P군에 비해 낮았다. 체내 포도당 제거 속도는 Sham+POD군이 $53.9{\pm}7.7$, Sham+P군이 $38.7{\pm}13.6$, Px+POD군이 $36.0{\pm}10.6$, Px+P군이 $29.2{\pm}6.8\;mg/kg$ 체중/min이었다. 체내 포도당 제거속도는 POD군이 P군에 비해 높았고, Px군이 Sham군에 비해 낮았다(P<0.01). Soleus 근육의 글리코겐 양은 POD군에서 P군에 비해 높았다. Px 백서에서는 soleus과 quadriceps 근육의 글리코겐 양은 정상군에 비해 낮았다. Soleus근육의 glycogen synthase의 활성은 P군에 비해 POD군에서 높았고(P<0.05), Px 백서가 Sham 백서에 비해 낮았다(P<0.05). Px 백서의 quadriceps 근육내 중성지방 축적량이 Sham 백서에 비해 높았는데, P에 비해 POD를 공급하였을 때 중성지방의 축적양이 낮아졌다. 결론적으로 POD은 당뇨와 정상 백서에서 인슐린 저항성을 감소시킴을 알 수 있었고 이러한 인슐린 저항성의 감소 현상은 근육에서의 glycogen synthase 활성과 관련이 있을 것으로 생각되었다.

• Nutritional Sciences
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• 제6권4호
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• pp.195-200
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• 2003

In recent years, the prevalence of type 2 diabetes mellitus has dramatically increased in Korea as the diet has rapidly become westernized. We determined the effect of long-term cola intakes on glucose metabolism and oxidative stress in weanling male Sprague Dawley rats consuming a moderate fat diet Thirty male rats, born from 6 female rats, were randomized into cola or water drinking groups. For 28 weeks, all rats were provided with an ad lib solid diet having 33 percent of its metabolisable energy as fat In addition, rats of the cola group were provided with ad lib cola instead of water. The daily total caloric intake did not differ between groups. The rats in the cola group consumed a higher proportion of carbohydrates, and their mean body weight and fasting serum insulin level were lower than that of the control group. Whole-body glucose disposal rates measured by an euglycemic hyperinsulinemic clamp were higher in the cola group. However, lipid peroxide levels in kidney tissue were higher in the cola group than in the control group. Superoxide dismutase activity in kidney tissues was lower in the cola group compared to the control group, while glutathion peroxidase and catalase activities were not significantly different between the two groups. In conclusion, long-term cola intakes decreased insulin resistance, but increased oxidative stress in kidney tissue due to decreased SOD activities, which may lead to kidney damage. Thus, moderate changes in insulin resistance may not affect the status of oxidative stress, and vice versa.

• 고려인삼학회:학술대회논문집
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• 고려인삼학회 2002년도 학술대회지
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• pp.129-144
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• 2002

We investigated anti-hyperglycemic and anti-obese effects of Panax ginseng berry extract and its major constituent, ginsenoside Re, in obese diabetic C57BL/6J ob/ob mice and their lean littermates. Animals received daily intraperitoneal injections of Panax ginseng berry extract for 12 days. On Day 5, 150 mg/kg extract-treated ob/ob mice had significantly lower fasting blood glucose levels compared to vehicle-treated mice $(156{\pm}9.0\;mg/dl\;vs.\;243{\pm}15.8mg/dl,$ P<0.01). On Day 12, the extract-treated ob/ob mice became normoglycemic $(137{\pm}6.7\;mg/dl)$ and had significantly improved glucose tolerance. The overall glucose excursion during the two-hour intraperitoneal glucose tolerance test (IPGTT), calculated as area under the curve (AUC), decreased by $46\%$ (P<0.01) compared to vehicle-treated ob/ob mice. Glucose levels of lean mice were not significantly affected by the extract. The improvement in blood glucose levels in 150 mg/kg extracttreated ob/ob mice was associated with significant reduction in serum insulin levels of fed and fasting mice. Consistent with an improvement in insulin sensitivity, hyperinsulinemic euglycemic clamp study revealed a more than 2-fold increase in the rate of insulin-stimulated glucose disposal in treated ob/ob mice $(112{\pm}19.1\;vs.\;52{\pm}11.8{\mu}mol/kg/min$ for the vehicle group, P<0.01). In addition, 150 mg/kg extract-treated ob/ob mice, but not the lean mice, lost significant weight (from $51.7{\pm}1.9g\;on\;Day\;0\;to\;45.7{\pm}1.2$ on Day 12, P<0.01 compared to vehicle-treated ob/ob mice), associated with a significant reduction in food intake (P<0.05) and a very significant increase in energy expenditure (P<0.01) and body temperature (P<0.01). A 12-day treatment with 150 mg/kg Panax ginseng berry extract also significantly reduced plasma cholesterol levels in ob/ob mice. Additional studies demonstrated that ginsenoside Re, a major constituent of the ginseng berry, but not from the root, plays a significant role in anti-hyperglycemic action. This anti-diabetic effect of ginsenoside Re was not associated with body weight changes, suggesting that other constituents in the extract have distinct pharmacological mechanisms on energy metabolism. The identification of a significant anti-hyperglycemic activity in ginsenoside Re may provide an opportunity to develop a novel class of anti-diabetic agent.

• 생명과학회지
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• 제34권1호
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• pp.1-8
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• 2024

Brain-type natriuretic peptide (BNP)은 뇌나트륨이뇨펩티드로, 좌심실의 심근세포에서 분비되는 호르몬으로, 심장과 신장에 작용하여 혈관 확장과 나트륨 이뇨 작용 등을 하는 것으로 알려져 있으나, 최근에는 다양한 조직에서 대사 작용을 조절하는 것으로 보고된다. 본 연구에서는 간 조직에서 BNP의 영향을 알기 위해 BNP가 고지방식이에 의해 유도되는 인슐린 저항성을 개선하는지를 조사하였다. BNP을 주입한 쥐와 control로서 saline을 주입한 쥐들 간에는 몸무게, 체지방양(fat mass), 제지방량(lean body mass)의 변화는 없었다. 고인슐린혈증 정상혈당 글루코스 클램프(Hyperinsulinemic Euglycemic Glucose Clam) 동안, BNP를 주입한 고지방 식이 쥐들은 saline을 주입한 고지방식이 쥐에 비해 혈당(blood glucose)은 감소하였으며, 포도당 주입 속도(glucose infusion rate)는 증가하였다. 또한 BNP은 포도당 신생 및 중성지방 합성 관련 유전자들의 발현을 감소시켜, 간에서 포도당 생성과 중성지방의 양을 감소시켰다. BNP는 saline을 주입한 쥐에 비해 간 조직에서 Akt와 AMP-activated protein kinase (AMPK)의 인산화를 증가시켰는데, 이는 BNP을 처리한 AML12 간세포에서도 BNP는Akt와 AMPK 인산화를 증가시켰다. 이상의 결과는 BNP가 간에서 인슐린 저항성을 개선하여 포도당 생성과 중성 지방 생성을 억제함을 알 수 있었다.

• The Korean Journal of Physiology and Pharmacology
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• 제4권1호
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• pp.25-31
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• 2000

ATP-sensitive potassium channels ($K_{ATP}$ channels) play an important role in insulin secretion from pancreatic beta cells. We have investigated the effect of propofol on $K_{ATP}$ channels in cultured single pancreatic beta cells of rats. Channel activity was recorded from membrane patches using the patch-clamp technique. In the inside-out configuration bath-applied propofol inhibited the $K_{ATP}$ channel activities in a dose-dependent manner. The half-maximal inhibition dose (ED50) was $48.6{\pm}8.4\;{\mu}M$ and the Hill coefficient was $0.73{\pm}0.11.$ Single channel conductance calculated from the slope of the relationship between single channel current and pipette potential $(+20{\sim}+100\;mV)$ was not significantly altered by propofol $(control:\;60.0{\pm}2.7\;pS,\;0.1\;mM\;propofol:\;58.7{\pm}3.5\;pS).$ However, mean closed time was surely increased. Above results indicate that propofol blocks the $K_{ATP}$ channels in the pancreatic beta cells in the range of its blood concentrations during anesthesia, suggesting a possible effect on insulin secretion and blood glucose level.

• Journal of Chest Surgery
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• 제24권11호
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• pp.1058-1067
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• 1991

High potassium cardioplegia is a widely accepted procedure to enhance myocardial protection from ischemic injuries associated with open heart surgery. Maintaining optimum osmolarity of the cardioplegic solution is one of the required conditions for an ideal cardioplegic solution Albumin is an frequently added component for maintaining optimum osmolarity of clinically used cardioplegic solutions. But the source of albumin is human blood so that the supply is limited and the cost of manufacturing is relatively high. Recently there are moves to minimized the use of blood product for fear of blood-associated infections or immunological disorders. In this experiment, we substituted mannitol or glucose for albumin added to the cardioplegic solution which has been used at the Wonju Medical College, To determine whether addition of mannitol or glucose instead of albumin in the cardioplegic solution can produce satisfactory myocardial protection during ischemia, three different groups of isolated rat heart perfused by modified Langendorff technique were studied. Wonju Cardioplegic Solution was selected as a standard high potassium[18mEq/L of K+] cardioplegic solution. Three kinds of cardioplegic solution were made by modifying the composition maintaining the same osmolarity[339$\pm$1mOsm/Kg] Isolated rat heart were perfused initially with retrograde nonworking mode and then changed to working mode. After measuring the heart rate, systolic aortic pressure, aortic flow, coronary flow, ischemic arrest by aorta cross clamp and cardioplegia was made maintaining the temperature of water jacket at 10oC. The heart was rewarmed and reperfused after 60min of ischemic arrest with intermittent cardioplegia at the 30min interval. The time to return of heart beat and the time required to get. Regular heart beat were observed after reperfusion. The recovery rate of the functional variables-heart rate, systolic aortic pressure, aortic flow, coronary flow and cardiac output were calculated and compared among the three groups of different cardioplegia-albumin, mannitol, and glucose. The wet weight and dry weight was measured and the water content of the heart as figured out for comparison. The time to return of heart beat was fastest in the albumin group, The functional recovery rates were best in the albumin group also. In the above conditions, albumin was the best additive to the cardioplegic solution compared to the mannitol or glucose.

• Journal of Nutrition and Health
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• 제34권5호
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• pp.485-492
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• 2001

The prevalence of type 2 diabetes mellitus has been rapidly increased in parallel with the westernization of eating behavior in Korea. Increased consumption of animal fat and simple sugar can be potential contributors for insulin resistance. The purpose of the study was to determine whether Western-(WD) and Korean-style(KD) diets altered insulin secretion and insulin resistance in male Sprague Dawley rats. Rats weighing 98$\pm$5g were provided by KD(77 En% of starch, 5 En% of corn oil and 13 En% of gluten plus 5 En% of casein), WD(42 En% of starch, 40 En% of butter and 18% of casein) or control diet(62 En% of starch, 20 En% of corn oil and 18% of casein) for 12 weeks. Body weights were lower in KD compared to WD. Fasting blood glucose levels were not different among diets. Insulin secretion from the beta cells was higher by 2.2$\pm$0.4 folds in WD than KD at baseline. In hyperglycemic clamp insulin secretion was higher in WD than KD and CD. Whole body glucose disposal rates referred to the state of insulin sensitivity were lowest in WD among groups. Glycogen deposits in soleus and quadriceps muscles were lowest in WD among all groups, but their triglyceride contents were highest. GLUT4 contents and glycogen synthase were lowest in WD in both muscles. In conclusions, westernization of diets needed more insulin to normalization of blood glucose levels due to increased insulin resistance. Thus, WD would lead to increased prevalence of diabetes mellitus when increased insulin resistance could not be compensated by insulin secretion in the case of elevated blood glucose levels. (Korean J Nutriton 34(5) : 485~492, 2001)

• BMB Reports
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• 제32권3호
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• pp.273-278
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• 1999

Cytolysin produced by Vibrio vulnificus has been known to be lethal to mice by increasing vascular permeability and neutrophil sequestration in the lung. In the present study, a cytotoxic mechanism of V. vulnificus cytolysin on the neutrophil was investigated. Cytolysin rapidly bound to neutrophils and induced cell death, as determined by the trypan blue exclusion test. V. vulnificus cytolysin caused the depletion of cellular ATP without the release of ATP or lactate dehydrogenase. Formation of transmembrane pores was evidenced by the rapid efflux of potassium and 2-deoxy-D-[$^3H$]glucose from cytolysin-treated neutrophils. It was further confirmed by the rapid flow of monovalent ions in the patch clamp of cytolysin-treated neutrophil membrane. The pore formation was accompanied by the oligomerization of cytolysin monomers on the neutrophil membrane as demonstrated by immunoblot, which exhibited a 210 kDa band corresponding to a tetramer of the native cytolysin of $M_r$ 51,000. These findings indicate that V. vulnificus cytolysin rapidly binds to the neutrophil membrane and oligomerizes to form small transmembrane pores, which induce the efflux of potassium and the depletion of cellular ATP leading to cell death without cytolysis.

• The Korean Journal of Physiology and Pharmacology
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• 제27권1호
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• pp.95-103
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• 2023

Rosiglitazone is a thiazolidinedione-class antidiabetic drug that reduces blood glucose and glycated hemoglobin levels. We here investigated the interaction of rosiglitazone with Kv3.1 expressed in Chinese hamster ovary cells using the wholecell patch-clamp technique. Rosiglitazone rapidly and reversibly inhibited Kv3.1 currents in a concentration-dependent manner (IC₅₀ = 29.8 µM) and accelerated the decay of Kv3.1 currents without modifying the activation kinetics. The rosiglitazonemediated inhibition of Kv3.1 channels increased steeply in a sigmoidal pattern over the voltage range of -20 to +30 mV, whereas it was voltage-independent in the voltage range above +30 mV, where the channels were fully activated. The deactivation of Kv3.1 current, measured along with tail currents, was also slowed by the drug. In addition, the steady-state inactivation curve of Kv3.1 by rosiglitazone shifts to a negative potential without significant change in the slope value. All the results with the use dependence of the rosiglitazone-mediated blockade suggest that rosiglitazone acts on Kv3.1 channels as an open channel blocker.

• 한국식품영양과학회지
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• 제36권2호
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• pp.186-193
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• 2007

The prevalence of diabetes has increased to 8% of population. Unlike type 2 diabetes in the western countries, Korean diabetic patients are nonobese and have low serum insulin levels. As the increased prevalence of diabetes and the peculiar characteristics may be related to dietary fat contents, we determined their effects on insulin resistance, insulin secretion and pancreatic $\beta-cell$ mass in 90% pancreatectomized (Px) diabetic rats in the present study. The rats were provided with low fat diet (LF, 10 energy% fat), moderate fat diet (MF, 25 energy% fat) and high fat diet (HF, 40 energy% fat) for 6 months. HF increased body weight and epidydimal fat pads parallel with increased food intake compared to LF and MF. Fasting serum glucose and insulin levels and homeostasis model assessment of insulin resistance were higher in HF, compared to LF and MF, indicating that HF increased insulin resistance. Rats fed LF and MF diets reduced insulin resistance, but only rats fed MF improved pancreatic $\beta-cell$ mass and insulin secretion capacity, measured by hyperglycemic clamp and in situ pancreatic perfusion. LF had low insulin secretion capacity and pancreatic $\beta-cell$ mass, indicating the increased possibility of diabetic prevalence and progression. MF increased $\beta-cell$ mass by stimulating $\beta-cell$ proliferation and neogenesis and reducing $\beta-cell$ apoptosis. In conclusion, MF is effective for the prevention of prevalence and progression of diabetes.