• Proceedings of the PSK Conference
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• 2002.10a
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• pp.342.3-343
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• 2002

Non-insulin dependent diabetes mellitus (NIDDM) is characterized by hyperglycemia, hyperinsulinemia. and impaired insulin action. Insulin resistance is considered to be the underlying mechanism in the pathogenesis of type 2 diabetes. which also leads to dyslipidemia, hypertension. and obesity. Thazolidinediones are a class of oral insulin-sensitizing agents that improve glucose utilization without increasing insulin release. They significantly reduce glucose, lipid and insulin levels in rodent models of NIDDM and obesity, and recent clinical data support theri efficacy in obese diabetic patients. (omitted)

• BMB Reports
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• v.34 no.4
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• pp.285-292
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• 2001

Insulin stimulates glucose uptake in muscle and adipose tissue and thus maintains normal blood glucose level in our body. Derangement of this process causes many grave health problems. Insulin stimulates glucose transport primarily by recruiting GLUT4 from its intracellular storage sites to the plasma membrane. The process is complex and involves GLUT4 trafficking through multiple subcellular compartments (organelles) and many protein functions, details of which are poorly understood. This review summarizes a recent development to isolate and characterize the individual intracellular GLUT4 compartments and to illustrate how this compartmental analysis will help to identify the insulin-sensitive step or steps in the insulin-induced GLUT4 recruitment in rat adipocytes. The review does not cover the recent exciting development in identification of many proteins implicated in this process.

• Journal of Ginseng Research
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• v.48 no.3
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• pp.276-285
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• 2024

Diabetes mellitus (DM) is a systemic disorder of energy metabolism characterized by a sustained elevation of blood glucose in conjunction with impaired insulin action in multiple peripheral tissues (i.e., insulin resistance). Although extensive research has been conducted to identify therapeutic targets for the treatment of DM, its global prevalence and associated mortailty rates are still increasing, possibly because of challenges related to long-term adherence, limited efficacy, and undesirable side effects of currently available medications, implying an urgent need to develop effective and safe pharmacotherapies for DM. Phytochemicals have recently drawn attention as novel pharmacotherapies for DM based on their clinical relevance, therapeutic efficacy, and safety. Ginsenosides, pharmacologically active ingredients primarily found in ginseng, have long been used as adjuvants to traditional medications in Asian countries and have been reported to exert promising therapeutic efficacy in various metabolic diseases, including hyperglycemia and diabetes. This review summarizes the current pharmacological effects of ginsenosides and their mechanistic insights for the treatment of insulin resistance and DM, providing comprehensive perspectives for the development of novel strategies to treat DM and related metabolic complications.

• Journal of the Korean Society of Food Science and Nutrition
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• v.33 no.6
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• pp.951-957
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• 2004

Hypoglycemic effect of Prunus mume (PM) extract containing in Sangjinyangheul-tang and Hwangkeumtang, one of the diabetic herbal medicines, was determined by investigating insulin-like action, insulin sensitizing action and a-glucoamylase suppressing action. Insulin-like activity of 3T3-L1 fibroblast was not shown with the treatment of PM methanol extracts. However, treatment with 20% or 40% PM methanol extracts and differentiation inducers significantly decreased the differentiation of 3T3-L1 fibroblasts to adipocytes. A significant insulin sensitizing activity was observed in 3T3-L1 adipocytes, giving PM extracts (60%, 80% and 100%) with 1 ng/mL insulin to reach glucose uptake level increased by 50 ng/mL of insulin alone. In addition, 20% and 40% methanol extracts of PM suppressed the a-glucoamylase activity by 30% in vitro. However, there was no significant differences in the peak of serum glucose levels and area under the curve in Sprague Dawley male rats treated with PM ethanol extract or cellulose and 2 g maltose or dextrin/kg body weight. These data suggested that PM extracts contain effective insulin sensitizing compounds, lipid synthesis suppressing compounds and possibly a-glucoamylase suppressing compounds. Therefore, PM extracts are beneficial for anti-diabetic treatment in obese diabetic patients.

• Asian-Australasian Journal of Animal Sciences
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• v.20 no.3
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• pp.385-392
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• 2007

A glucose clamp technique was used to compare dietary starch (ST), starch plus sucrose (ST+SU) and sucrose (SU) with regard to the effect on tissue responsiveness and sensitivity to insulin in intact adult male goats. The goats were fed diets containing 1.2 times of ME and CP for maintenance requirements twice daily for 21 d. Of the energy intake, 30% was offered with ST, ST+SU or SU for the respective diets, and 70% as alfalfa hay, ground corn and ground soybean meal at the respective weight ratio of 1, 1, and 0.3 for all diets. Tissue responsiveness and sensitivity to insulin were evaluated using a hyperinsulinemic euglycemic clamp technique with four levels of insulin infusion beyond 13 h after feeding. The concentrations of plasma metabolites and insulin were also determined at 3, 6 and 13 h after feeding to evaluate the effects of different carbohydrates on metabolic states in the body. Plasma glucose concentration was higher (p = 0.01) for SU diet than for ST and ST+SU diets. Increasing SU intake decreased (p<0.01) plasma acetate concentration across the time. At 3 h but not 6 and 13 h after feeding, high lactate (p = 0.01), and non-significant high propionate (p = 0.14) and low urea nitrogen (p = 0.19) concentrations were observed in plasma on SU compared with ST and ST+SU diets. Plasma insulin concentration was not different (p = 0.44) between ST and SU fed animals. In the glucose clamp experiment, considering the effects on the maximal glucose infusion rate (tissue responsiveness to insulin, p = 0.54) and the plasma insulin concentration at half-maximal glucose infusion rate (insulin sensitivity, p = 0.54), SU was not different from ST. It is concluded that SU may not be greatly different from ST with regard to the effect on tissue responsiveness and sensitivity to insulin in adult goats when fed twice daily as part of a high-concentrate diet. The possible greater effects of SU on plasma metabolites concentrations at 3 h than at 6 and 13 h after feeding suggest that a lack of persistency of SU effects during the postfeeding period may be associated with the poor response to SU in insulin action.

• The Korean Journal of Physiology
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• v.27 no.2
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• pp.123-138
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• 1993

The mechanism of insulin action to increase glucose transport is attributed to glucose transporter translocation from intracellular storage pools to the plasma membrane in insulin-sensitive cells. The present study was designed to visualize the redistribution of the glucose transporter by means of an immunogold labelling method. Our data clearly show that glucose transporter molecules were visible by this method. According to the method this distribution of glucose transporters between cell surface and intracellular pool was different in adipocytes. The glucose transporter molecules were randomly distributed at the cell surface whereas the molecules at LDM were farmed as clusters. By insulin treatment the number of homogeneous random particles increased at the cell surface whereas the cluster forms decreased at the intracellular storage pools. It suggests that the active molecules needed to be evenly distributed far effective function and that the inactive molecules in storage pools gathered and termed clusters until being transferred to the plasma membrane.

• Toxicological Research
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• v.8 no.1
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• pp.9-15
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• 1992

Hydroxybrazilin was examined for its effects on glycogen synthesis in primary cultured rat hepatocytes. At 10-6 M hydroxybrazilin, glycogen synthesis was increased in basal state, but not in insulin stimulated state. However, any signiFicant changes were nor observed at 10-5 M hydroxybrazilin in both states. The glycogen synthesis was rather suppressed at 10-5M hydroxybrazilin. It was also observed that hydroxybrazilin increased insulin sensitivity but not insulin responsiveness at 10-5M concentration. These results suggest that hydroxybrazilin might exert hypoglycemic action through its effects on insulin receptor and post receptor events.

• Journal of Ginseng Research
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• v.21 no.3
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• pp.174-186
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• 1997

In this study, rat hepatocytes known to have active carbohydrate metabolism were obtained by using the liver perfusion technique to examine the hypoglycemic action of red ginseng saponin components [ginsenoside (mixture, $Rb_1$, and $Rg_1$)] and incubated in two different media-one containing insulin and glucagon (control group), and the other containing glucagon only, The specific activities of some regulatory enzymes such as glucokinase, glucose 6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase, and glucose 6-phosphatase, in main pathways which were directly related to the glucose metabolism were compared between these two kinds of hepatocytes cultured in two different media. The effects of red ginseng saponin components [ginsenoside (mixture, $Rb_1$, and $Rg_1$)] under the concentration of $10^3$~$10^6$% on these enzymes In hepatocytes were also investigated, when they were added to these two media. The results were as follows. The specific activity of enzymes such as glucokinase, glucose 6-phosphate dehydrogenase, and 6-phosphogluconate dehydrogenase related to glucose-consuming pathways of insulin-deficient group was much less than control one, however, their decreased activity was recovered after the addition of ginseng components at all range of concentrations. The increased specific activity of these on - zymes was shown by the addition of ginseng components to the control group. On the other hand, the specific activity of glucose 6-phosphatase related to glucose-producing pathway of insulin-deficient group was much higher than control one, but their Increased activity was decreased after the addition of ginseng components at all range of concentrations. The same results were obtained after the addition of ginseng components to the control group. These results suggest that the red ginseng saponin components might better diabetic hyperglycemia by regulating the activity of enzymes related to glucose metabolism directly and/or Indirectly though more detailed studies were needed.

• Asian-Australasian Journal of Animal Sciences
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• v.19 no.7
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• pp.1010-1018
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• 2006

A glucose clamp technique was used to investigate the effects of non-protein energy intake on tissue responsiveness and sensitivity to insulin for glucose metabolism in intact adults male goats. Three goats were fed diets at 1.0, 1.5 and 2.0 times of ME for maintenance, each for 21 d. Crude protein intake was 1.5 times of maintenance requirement in each treatment. Tissue responsiveness and sensitivity to insulin were evaluated using a hyperinsulinemic euglycemic clamp technique with four levels of insulin infusion, beginning at 13 h after feeding. Concentrations of plasma metabolites and insulin were also measured at 3, 6 and 13 h after feeding, for evaluating effects of non-protein energy intake on the metabolic status of the animals. Increasing non-protein energy intake prevented an increase in plasma NEFA concentration at 13 h after feeding (p = 0.03). Plasma urea-nitrogen and total amino-nitrogen concentrations decreased (p<0.01) and increased (p = 0.03), respectively, with increasing non-protein energy intake across time relating to feeding. Plasma insulin concentration was unaffected (p = 0.43) by non-protein energy intake regardless of time relating to feeding. In the glucose clamp experiment, increasing non-protein energy intake decreased numerically (p = 0.12) the plasma insulin concentration at half-maximal glucose infusion rate (insulin sensitivity), but did not affect (p = 0.60) maximal glucose infusion rate (tissue responsiveness to insulin). The present results suggest that an increase in non-protein energy intake may enhance insulin sensitivity for glucose metabolism, unlike responsiveness to insulin, in adult male goats. The possible enhancement in insulin sensitivity may play a role in establishing anabolic status in the body, when excess energy is supplied to the body.

• Proceedings of the Ginseng society Conference
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• 1984.09a
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• pp.191-197
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• 1984

A further purified fraction (D-O-ANa) was obtained from DPG 3-2 fraction of Ginseng Radix by complete removal of saponins, nucleosides, nucleic acid bases, amino acids, and sugars. D-O-ANa - induced insulin release was investigated to compare with that of DPG 3-2 and other isolated components. Among the sub fractions of DPG 3-2, D-O-ANa exhibited the most potent release of insulin with or without high concentrations of glucose, and it particularly enhanced the second phase of glucose-induced insulin release. DGP 3-2 potentiated significantly the glucose-induced insulin release from the isolated islets of diabetic mice at increasing concentrations of extracellular calcium ions (0.16 - 2.5 mM). A definite relationship was found between calcium $(^{45}Ca)$ uptake and insulin release. Ginsenoside $(G)-Rb_1\;and\;G-Rg_1$ did not enhance the glucose-induced insulin release. The effect of ginseng saponins was blocked by glucose (16.7 mM), being distinctly different from the glucose-potentiated effect of DPG 3-2. The insulin release effect of $G-Rg_1$ was unaffected by the presence or absence of extracellular $Ca^{2+}$ and theophylline. Adenosine also increased insulin release from isolated islets, but had no effect on perfused rat pancreas. Arginine stimulated insulin release less evidently than D-O-ANa, though arginineand adenosine-induced glucagon releases were more remarkable. In conclusion, D-O-ANa appears to be a major fraction in insulin release activity of ginseng and its mode of action may be related to $Ca^{2+}$ ion uptake. This physiological mechanism was distinct from that of the abnormal release induced by ginseng saponins.