• Nutrition Research and Practice
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• v.11 no.3
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• pp.198-205
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• 2017

BACKGROUND/OBJECTIVES: The anti-diabetic activity of pear through inhibition of ${\alpha}-glucosidase$ has been demonstrated. However, little has been reported about the effect of pear on insulin signaling pathway in obesity. The aims of this study are to establish pear pomace 50% ethanol extract (PPE)-induced improvement of insulin sensitivity and characterize its action mechanism in 3T3-L1 cells and high-fat diet (HFD)-fed C57BL/6 mice. MATERIALS/METHODS: Lipid accumulation, monocyte chemoattractant protein-1 (MCP-1) secretion and glucose uptake were measure in 3T3-L1 cells. Mice were fed HFD (60% kcal from fat) and orally ingested PPE once daily for 8 weeks and body weight, homeostasis model assessment of insulin resistance (HOMA-IR), and serum lipids were measured. The expression of proteins involved in insulin signaling pathway was evaluated by western blot assay in 3T3-L1 cells and adipose tissue of mice. RESULTS: In 3T3-L1 cells, without affecting cell viability and lipid accumulation, PPE inhibited MCP-1 secretion, improved glucose uptake, and increased protein expression of phosphorylated insulin receptor substrate 1 [p-IRS-1, ($Tyr^{632})$)], p-Akt, and glucose transporter type 4 (GLUT4). Additionally, in HFD-fed mice, PPE reduced body weight, HOMA-IR, and serum lipids including triglyceride and LDL-cholesterol. Furthermore, in adipose tissue, PPE up-regulated GLUT4 expression and expression ratio of p-IRS-1 ($Tyr^{632})/IRS$, whereas, down-regulated p-IRS-1 ($Ser^{307})/IRS$. CONCLUSIONS: Our results collectively show that PPE improves glucose uptake in 3T3-L1 cells and insulin sensitivity in mice fed a HFD through stimulation of the insulin signaling pathway. Furthermore, PPE-induced improvement of insulin sensitivity was not accompanied with lipid accumulation.

• YAKHAK HOEJI
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• v.38 no.3
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• pp.238-249
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• 1994

The purpose of this research was to investigate effects of baicalin on the differentiation of preadipocytes, 3T3-L1, and to characterize the action of baicalin that affect the responses of 3T3-L1 cells during differentiation. In various culture conditions, effects of baicalin and adrenoreceptor agonists such as phenylephrine(PE) and isoproterenol(IPR) on cell differentiation were examined. Also, effects of the drugs on differentiation, triglyceride(TG) contents, expression of insulin receptor, cAMP contents, the cytosolic $Ca^{2+}$ levels, and amount of calmodulin(CaM) were examined. The results suggest that baicalin has adrenergic receptor blocking activity during the process of differentiation of 3T3-L1 cells and that in the early stage of the adipose conversion, the effect of baicalin on the adipocyte differentiation is mediated by the regulation of insulin receptor expression, but by alterations of the cAMP and the calcium metabolism in the late stage. These results also suggest that the action of baicalin may be significant in the lipid metabolism, lipogenic and lipolytic pathways, of adipose cells.

• The Korean Journal of Physiology and Pharmacology
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• v.4 no.2
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• pp.91-97
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• 2000

The purpose of the present study was to determine the preventive effects of combined interventional trial of fish oil treatment and exercise training on insulin resistance of skeletal muscle in high-fat fed rats. Male Wistar rats were randomly divided into chow diet (CD), high-fat diet (HF), high-fat diet with fish oil (FO), high-fat diet with exercise training (EX), and FO+EX groups. The rats in control group were fed chow diet containing, as percents of calories, 58.9% carbohydrate, 12.4% fat, and 28.7% protein. High-fat diet provided 32% energy as lard, 18% as corn oil, 27% as carbohydrate and 23% as casein. The fish oil diet had the same composition as the high fat diet except that 100 g menhaden oil was substituted for corn oil. Insulin sensitivity was assessed by in vitro glucose transport in the soleus muscle after diet treatment and treadmill running for 4 weeks. While the FO or EX only partially prevented insulin resistance on glucose transport and visceral obesity induced by high-fat diet, these interventions completely corrected hyperinsulinemia and hyperglycemia from the high-fat diet. The rats in the FO+EX showed normalized insulin action on glucose transport, plasma chemicals and visceral fat mass. Insulin-mediated glucose transport was negatively associated with total visceral fat mass (r=－0.734; p＜0.000), plasma triglyceride (r=－0.403; p＜0.05) and lepin (r=－0.583; p＜0.001) concentrations with significance. Multiple stepwise regression analysis showed that only total visceral fat mass was independently associated with insulin-mediated glucose transport (r=－0.668; p＜0.000). In conclusion, combined interventional trial of FO+EX recovered insulin resistance on glucose transport of skeletal muscle induced by high-fat diet. Visceral fat mass might be more important factor than plasma TG and leptin to induce insulin resistance on glucose transport of skeletal muscle in high-fat fed rats.

• BMB Reports
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• v.44 no.3
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• pp.205-210
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• 2011

Insulin has antiapoptotic activity in various cell types. However, the signaling pathways underlying the antiapoptotic activity of insulin is not yet known. This study was conducted to determine if cAMP affects the antiapoptotic activity of insulin and the activity of PI3K and ERK in CHO cells expressing human insulin receptors (CHO-IR). Insulin-stimulated ERK activity was completely suppressed by cAMP-elevating agents like as pertussis toxin (Ptx) and cholera toxin (Ctx) after 4 h treatment. Insulin-stimulated PKB/Akt activity was not affected at all. Ptx treatment together with insulin increased the number of apoptotic cells and the degree of DNA fragmentation. Ctx or 8-br-cAMP treatment also increased the number of apoptotic cells and stimulated the cleavage of caspase-3 and the hydrolysis of PARP. Taken together, cAMP antagonizes the antiapoptotic activity of insulin and the main target molecule of cAMP in this process is likely ERK, not PI3K-dependent PKB/Akt.

• Archives of Pharmacal Research
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• v.13 no.4
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• pp.359-364
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• 1990

The present study was performed to evaluate the hypoglycemic mechanism of brazilin. Brazilin significantly reduced plasma glucose level in streptozotocin induced diabetie rats and this effect seems to be mediated by extrapancratic effects rather than by pacreatic effect because no significant changes were observed in plasma insulin levels. The rates of glycogen synthesis, glycolysis and glucose oxidation in soleus muscle were markedly increased following brazilin treatment to diabetic animals. Glucose transport seemed to be increased by the treatment of brazilin. Brazilin did not affect insulin binding to muscles from streptozotiocin induced diabetic rats. These results suggest that potentiation of periopheral glucose utilization may be one of the major causes of hypoglucemic action of brazilin.

• Journal of Ginseng Research
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• v.16 no.3
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• pp.198-209
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• 1992

The decreased activities of liver enzymes relating to carbohydrate metabolism such as glucose- 6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase and acetyl CoA carboxylase of streptozotocin injected rats were significantly modified by the intraperitoneal injection of ginseng saponin mixture and/or purified ginsenosides. However, several enzymes such as pyruvate kinase, malic enzyme and glycogen phosphorylase were not modified appreciably by the saponin administration, suggesting that the effect of ginseng saponin might be depend upon individual enzymes. Examination of liver enzymes by liver professing technique using perfusion buffer containing saponin (10-3%) showed that the ginseng saponin might stimulate insulin biosynthesis as well as the related enzyme activities.

• Journal of Yeungnam Medical Science
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• v.12 no.2
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• pp.319-330
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• 1995

The influence of normal late pregnancy on insulin action and insulin secretion was studied in the Sprague-Dawley female rats. On 20th day after mating, intravenous glucose tolerance test(IVGTT) was performed in non pregnant control and pregnant rats. As results of IVGTT, glucose disappearance rate was not significantly different in both groups, but secretory response of insulin was significantly(p<0.05) increased in pregnant rat. And the ratio of insulin/glucose was significantly higher in pregnant rats, which means existence of insulin resistance. These insulin resistance was overcomed by increased secretory response of pancreatic insulin. Insulinogenic index(${\Delta}$ insulin/glucose - 5 min) was highly significantly (r=0.62, p<0.01) correlated with progesterone concentration. Glycogen level and amounts of $^{14}C$-glucose incorporated into glycogen after IVGTT were significantly(p<0.05) decreased in the liver, but were not changed significantly in soleus. Glycogen synthase activity of soleus and liver was not differ significantly in the both groups. Insulin binding at varying concentrations of insulin to crude membrane of pregnant liver was not significantly different from control. In conclusions, although these pregnant rats were normal glucose tolerance due to increased secretory response of insulin, that was correlated with progesterone concentration, pregnant rat had insulin resistance. The mechanisms of insulin resistance were not related to defect of insulin binding phase and glycogen synthase, but suggest pre-receptor and/or postreceptor phase.

• Journal of Pharmacopuncture
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• v.20 no.4
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• pp.235-242
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• 2017

Irisin is a novel hormone like polypeptide that is cleaved and secreted by an unknown protease from fibronectin type III domain-containing protein 5 (FNDC5), a membrane-spanning protein and which is highly expressed in skeletal muscle, heart, adipose tissue, and liver. Since its discovery in 2012, it has been the subject of many researches due to its potent physiological role. It is believed that understanding irisin's function may be the key to comprehend many diseases and their development. Irisin is a myokine that leads to increased energy expenditure by stimulating the 'browning' of white adipose tissue. In the first description of this hormone, increased levels of circulating irisin, which is cleaved from its precursor fibronectin type III domain-containing protein 5, were associated with improved glucose homeostasis by reducing insulin resistance. Irisin is a powerful messenger, sending the signal to determine the function of specific cells, like skeletal muscle, liver, pancreas, heart, fat and the brain. The action of irisin on different targeted tissues or organs in human being has revealed its physiological functions for promoting health or executing the regulation of variety of metabolic diseases. Numerous studies focus on the association of irisin with metabolic diseases which has gained great interest as a potential new target to combat type 2 diabetes mellitus and insulin resistance. Irisin is found to improve insulin resistance and type 2 diabetes by increasing sensitization of the insulin receptor in skeletal muscle and heart by improving hepatic glucose and lipid metabolism, promoting pancreatic ${\beta}$ cell functions, and transforming white adipose tissue to brown adipose tissue. This review is a thoughtful attempt to summarize the current knowledge of irisin and its effective role in mediating metabolic dysfunctions in insulin resistance and type 2 diabetes mellitus.

• Proceedings of the Ginseng society Conference
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• 1978.09a
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• pp.75-77
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• 1978

It was found that water extract of Panax ginseng strongly inhibited adrenaline-induced lipolysis in isolated fat cells of rat epididymal adipose tissue. An antilipolytic action of the water extract was easily inactivated by treatment with pronase, suggesting that the active principle might be a protein or a peptide. Experiments were designed to purify the antilipolytic substance, or insulin-like substance, of the water extract. The water extract was dialyzed against disti'led water. The outer dialysate was subjected to DEAE-cellulose column chromatography, gelfuaration on sephadex G-50 column, avicel cellulose column chromatography and phospho-cellulose column chromatography, successively. The finally purified substance gave one spot on thin layer chromatography. The molecular weight was found to be around 1000. Experiments are now in progress to elucidate the structure of this insulin-like peptide.

• The Korean Journal of Physiology and Pharmacology
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• v.20 no.6
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• pp.581-593
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• 2016

The advantages of monounsaturated fatty acids (MUFAs) on insulin resistance and type 2 diabetes mellitus (T2DM) have been well established. However, the molecular mechanisms of the anti-diabetic action of MUFAs remain unclear. This study examined the anti-hyperglycemic effect and explored the molecular mechanisms involved in the actions of fish oil- rich in MUFAs that had been acquired from hybrid catfish (Pangasius larnaudii${\times}$Pangasianodon hypophthalmus) among experimental type 2 diabetic rats. Diabetic rats that were fed with fish oil (500 and 1,000 mg/kg BW) for 12 weeks significantly reduced the fasting plasma glucose levels without increasing the plasma insulin levels. The diminishing levels of plasma lipids and the muscle triglyceride accumulation as well as the plasma leptin levels were identified in T2DM rats, which had been administrated with fish oil. Notably, the plasma adiponectin levels increased among these rats. The fish oil supplementation also improved glucose tolerance, insulin sensitivity and pancreatic histological changes. Moreover, the supplementation of fish oil improved insulin signaling ($p-Akt^{Ser473}$ and p-PKC-${\zeta}/{\lambda}^{Thr410/403}$), $p-AMPK^{Thr172}$ and membrane GLUT4 protein expressions, whereas the protein expressions of pro-inflammatory cytokines (TNF-${\alpha}$ and nuclear NF-${\kappa}B$) as well as p-PKC-${\theta}^{Thr538}$ were down regulated in the skeletal muscle. These data indicate that the effects of fish oil-rich in MUFAs in these T2DM rats were partly due to the attenuation of insulin resistance and an improvement in the adipokine imbalance. The mechanisms of the anti-hyperglycemic effect are involved in the improvement of insulin signaling, AMPK activation, GLUT4 translocation and suppression of pro-inflammatory cytokine protein expressions.