• Journal of Pharmaceutical Investigation
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• 제12권3호
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• pp.88-92
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• 1982

Insulin administration rectally with the liposome has the hypoglycemic effect in the rabbits. The reducton in blood sugar was maximum at about 60 minutes after administration and continued for 4 hrs. at low level in these experiments. No hypoglycemic effect was observed in control administrated rectally without liposome. Rectal absorption of insulin has been effected by addition of the bile salt, as the protective agent which prevented denaturation and the phastransition of insulin in liposome-encapsulation. As a matter of the fact, a significant hypoglycemic action was obtained when the insulin-liposome was given by rectal administration. The use of this agent to enhance insulin absorption offers the possibility of a new approach to rectal insulin therapy.

• Archives of Pharmacal Research
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• 제29권9호
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• pp.768-776
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• 2006

Non-alcoholic fatty liver disease (NAFLD) is common in obesity. However, weight reduction alone does not prevent the progression of NAFLD to end-stage disease associated with the development of cirrhosis and liver disease. In a previous experiment, 50% ethanol extract of Acanthopanax senticosus stem bark (ASSB) was found to reduce body weight and insulin resistance in high fat diet-induced hyperglycemic and hyperlipidemic ICR mice. To evaluate the anti-steatosis action of ASSB, insulin-resistant ob/ob mice with fatty livers were treated with ASSB ethanol extract for an 8 week-period. ASSB ethanol extract reversed the hepatomegaly, as evident in reduction of % liver weight/body weight ratio. ASSB ethanol extract also specifically lowered circulating glucose and lipids, and enhanced insulin action in the liver. These changes culminated in inhibition of triglyceride synthesis in non-adipose tissues including liver and skeletal muscle. Gene expression studies confirmed reductions in glucose 6-phosphatase and lipogenic enzymes in the liver. These results demonstrate that ASSB ethanol extract is an effective treatment for insulin resistance and hepatic steatosis in ob/ob mice by decreasing hepatic lipid synthesis.

• 한국임상수의학회지
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• 제28권1호
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• pp.139-143
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• 2011

A Spitz (5-years old, castrated male) and a Maltese (9-years old, castrated male) were presented with weight loss, polyuria/polydipsia (PU/PD) and depression. Diabetic ketosis was diagnosed based on clinical signs, physical examinations and screening tests (CBC, serum chemistry and urinalysis). The dogs were treated with NPH initially. However, NPH was inadequate to control blood glucose level due to the short duration of the action (< 5 hours). Because of the poor glycemic control with NPH, the dogs showed diabetic complications including weight loss and cataract. After change to glargine, the duration of insulin action was extended up to 11 hours. As a result, there was significant improvement in clinical signs and serum fructosamine concentrations. This study suggests that glargine is useful as a long-acting insulin in dogs which have poor glycemic control due to the short duration of NPH.

• The Korean Journal of Physiology and Pharmacology
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• 제1권1호
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• pp.83-90
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• 1997

Aim of this study was to investigate if pancreatic polypeptide (PP) reduced the insulin action via the intra-pancreatic cholinergic nerves in the isolated rat pancreas. The pancreas was isolated from rats and perfused with intra-arterial infusion of modified Krebs-Henseleit solution containing 2.5 mM glucose at a flow rate of 1.2 ml/min. Simultaneous intra-arterial infusion of insulin (100 nM) resulted inpotentiation of the pancreatic flow rate and amylase output which were stimulated by cholecystokinin (CCK, 14 pM). These potentiating actions of insulin on the CCK -stimulated pancreatic exocrine secretion were completely abolished by administration of rat PP. Vesamicol, a potent inhibitor of vesicular acetylcholine storage, and tetrodotoxin (TTX) also significantly reduced the combined actions of insulin and CCK. Administration of carbamylcholine, an acetylcholine agonist, completely restored the vesamicol- or TTX-induced inhibition of the potentiation between insulin and CCK. Also rat PP failed to attenuate the restoring effect of carbamylcholine. Electrical field stimulation (15-30 V, 2 msec and 8 Hz) resulted in a significant increase in the pancreatic flow rate and amylase output in voltage-dependent manner. Effects of electrical field stimulation were augmented by endogenous insulin. Rat PP also suppressed the pancreatic exocrine secretion stimulated by electrical field stimulation. These observations strongly suggest that PP inhibits the potentiating actions of insulin on CCK -stimulated pancreatic exocrine secretion by suppression of the intra-pancreatic cholinergic activity in the isolated rat pancreas.

• The Korean Journal of Physiology and Pharmacology
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• 제3권3호
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• pp.357-364
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• 1999

We investigated the role of $Ca^{2+}$ and protein kinases/phosphatases in the stimulatory effect of insulin on glucose transport. In isolated rat adipocytes, the simple omission of $CaCl_2$ from the incubation medium significantly reduced, but did not abolish, insulin-stimulated 2-deoxy glucose (2-DG) uptake. Pre-loading adipocytes with intracellular $Ca^{2+}$ chelator, 5,5'-dimethyl bis (o-aminophenoxy)ethane-N,N,N'N' tetraacetic acetoxymethyl ester (5,5'-dimethyl BAPTA/AM) completely blocked the stimulation. Insulin raised intracellular $Ca^{2+}$ concentration $([Ca^{2+}]_i)$ about 1.7 times the basal level of $72{\pm}5$ nM, and 5,5'-dimethyl BAPTA/AM kept it constant at the basal level. This correlation between insulin-induced increases in 2-DG uptake and $[Ca^{2+}]_i$ indicates that the elevation of $[Ca^{2+}]_i$ may be prerequisite for the stimulation of glucose transport. Studies with inhibitors (ML-9, KN-62, cyclosporin A) of $Ca^{2+}-calmodulin$ dependent protein kinases/phosphatases also indicate an involvement of intracellular $Ca^{2+}.$ Additional studies with okadaic acid and calyculin A, protein phosphatase-1 (PP-1) and 2A (PP-2A) inhibitors, indicate an involvement of PP-1 in insulin action on 2-DG uptake. These results indicate an involvement of $Ca^{2+}-dependent$ signaling pathway in insulin action on glucose transport.

• Journal of Ginseng Research
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• 제22권1호
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• pp.51-59
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• 1998

In this study, rat hepatocytes known to have active glucose metabolism were obtained to investigate the hypoglycemic action of fat soluble fraction of red ginseng by using the liver perfusion technique and incubated in two different media-one containing insulin and glucagon (control group), and the other containing glucagon only The activities of main regulating enzymes, such as glucokinase, glucose 6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenate, and glucose 6-phosphatase, related to metabolic pathways of glucose in these two kinds of hepatocytes were compared between these two groups and the effects of addition of fat soluble fraction ($10^1$~$10^4$%) from red ginseng to these two groups on these enzymes were also detected. The results were as follows. The specific activity of enzymes such as glucokinase, flucorse 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 fat-soluble fraction at all range of concentrations. The specific activity of these enzymes after the addition of ginseng components to the control group was also increased. 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 obviously after the addition of fat soluble fraction at all range of concentrations. The same results were observed after the addition of fat-soluble fraction to the control group. These results suggest that the red ginseng saponin components might be effective on diabetic hyperglycemia by regulating the activity of enzymes related to glucose metabolism directly and/or indirectly. The effects of fat-soluble fraction ($10^2$%) and ginsenosides (mixture, $Rb_1$ and $Rg_1$, $10^4$%) on hypoglycemic action were compared. As a result, they showed considerable effect on hyperglycemia, but the best eff ect on the activities of glucokinase and glucose 6-phosphate dehydrogenase was appeared by ginsenoside $Rb_1$ and that of 6-phosphogluconate dehydrogenase and glucose 6-phosphatase was by ginsenoside mixture.

• 대한약리학회지
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• 제29권2호
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• pp.253-261
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• 1993

Streptozotocin으로 당뇨병을 유발시킨 흰쥐를 모델로 하여 당뇨병으로 인한 인슐린의 antilipolytic action을 매개하는 insulin-sensitive cyclic nucleotide phosphodiesterase의 역할의 변화 가능성을 연구하였다. 흰쥐의 epididymal adipose tissue로부터 분리한 지방세포를 여러 약물과 toxin으로 전처치한 다음, insulin을 처치 또는 처치하지 않고 $37^{\circ}C$에서 15분 동안 incubation하였다. 그리고 나서 differential centrifugation으로 3 fractions로 분리한 다음 cAMP phosphodiesterase activity를 assay하였다. Insulin에 의한 PDE activities의 증가는 당뇨병군과 대조군 모두 crude microsomal (P2) fraction에서만 볼 수 있었다. P2 fraction을 2 nM insulin, $100\;{\mu}M$ isoproterenol, 또는 두 약물을 함께 처치하여 나타난 maximal effect는 두 군 모두에서 유의한 차이가 없었다. 그러나 basal PDE activities는 당뇨병균이 대조군에 비해 증가한 것으로 나타났다. 당뇨병군의 P2 fraction의 insulin-sensitive PDE activities는 $A_{1}$ adenosine receptor agonist 인 PIA에 의해서 영향을 받지 않은 반면, 대조군의 경우 PIA에 의해 basal PDE activities와 같게 감소하였다. 그리고 지방세포의 pertussis toxin에 대한 sensitivity는 당뇨병군이 대조군보다 더욱 민감하였다. 그러나 cholera toxin에 대한 sensitivity는 당뇨병군과 대조군 사이에 큰 차이를 볼 수 없었다. 이러한 결과로 보아 streptozotocin으로 당뇨병을 유발시킨 흰쥐의 지방세포에서, adenosine receptor와 같은 inhibitory receptor를 경유한 signalling의 감소는 $G_{i}$ proteins의 소실 또는 기능의 감소와 관련이 있으며, 또한 basal state에서 insulin-dependent PDE의 활성을 증가시키는 것으로 사료된다.

• 대한약학회:학술대회논문집
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• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2-2
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• pp.187.1-187.1
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• 2003

Type 2 diabetes is characterized by high level of blood glucose and insulin and impaired action. In recent years, the treatment of type 2 diabetes has been revolutionized with the advent of thiazolidinedione (TZD) class of molecules that ameliorate insulin resistance and thereby normalize elevated blood glucose levels. These TZDs are synthetic, high-affinity ligands of peroxisome proliferator activated receptor-gamma (PPAR${\gamma}$); a member of the nuclear receptor family that controls the expression of genes in the target tissues of insulin action. (omitted)

• Archives of Pharmacal Research
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• 제25권6호
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• pp.923-931
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• 2002

Sopungsungi-won (SP) is a known for\mula for senile constipation and diabetes mellitus, based on traditional Korean medicine. The preventive effect of SP on the development of overt diabetes in Zucker diabetic fatty (ZDF) rats was evaluated. When administered orally through a diet for 8 weeks, diabetic conditions such as hyperglycemia, polydipsia and hypertriglyceridemia were all ameliorated in SP-treated rats. In parallel with the onset and progression of hyperglycemia in the ZDF control rats; there was a marked decline in plasma insulin concentrations from 26.1 $\mu$U/ml, at age 7 weeks, to 14.8 $\mu$U/ml at age 15 weeks. In the SP-treated rats, however, the plasma insulin concentrations did not decline, and SP at a dose of 5 g/kg significantly increased the insulin levels to 31.9 $\mu$U/ml. Early normalization of plasma insulin and a retained ability to subsequently increase plasma insulin were indicative of a pancreatic $\beta$ cell protective action by the SP for\mula. In addition, expressions of an insulin-responsive gene and corresponding protein, glucose transporter 4 (GLUT4), in skeletal \muscle, were also determined in SP- and rosiglitazone-treated ZDF rats. mRNA and protein levels of GLUT4 in SP-treated rats were upregulated in a dose dependent manner. Furthermore, when ZDF rats were treated with 2 g/kg of the SP for\mula, the activity of glucose-6-phosphatase was decreased by 49%, whereas the activity of glucokinase was increased by 196%, compared to the ZDF control rats. Taken together, these data provide evidence that the SP for\mula markedly lowered the plasma glucose levels, probably through an effect not only on improvement of insulin action, but through a combined sti\mulation of glycolysis and an inhibition of gluconeogenesis in the liver, and also suggest the validity of SP's clinical use in the treatment of type 2 diabetes mellitus following further toxicological investigation.

• 대한의생명과학회지
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• 제15권4호
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• pp.301-307
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• 2009

Whole-body insulin resistance results largely from impaired insulin-stimulated glucose disposal in skeletal muscle. Our previous studies using differential display and quantitative real-time RT-PCR have shown that a novel cDNA band (DD23) had a higher level of expression in insulin resistant skeletal muscle and it was correlated with whole-body insulin action, independent of age, sex, and percent body fat. In this study, we cloned and characterized DD23. The DD23 sequence is part of the 3'UTR region of the RNA binding motif, single stranded interacting protein (RBMS3). We have cloned the full length cDNA for RBMS3 and identified two splice variants. These variants named DD23-L and DD23-S have 15 and 14 exons respectively and differ from RBMS3 in the 3'UTR significantly. Northern blot analyses showed that an ~8.8 kb mRNA transcript of DD23 was predominantly expressed in skeletal muscle and to a lesser extent in placenta, but not in heart, brain, lung, liver, or kidney, unlike RBMS3. Elevated expression levels of these novel alternatively spliced variants of RBMS3 in skeletal muscle may play a role in whole body insulin resistance.