• 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.

• 보건교육건강증진학회지
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• 제26권2호
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• pp.149-155
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• 2009

Metabolically obese but normal weight(MONW) syndrome is characterized, with potentially increased risks for development of the insulin resistance or metabolic syndrome despite their normal body mass index(BMI) < 25 kg/m2. Such characteristics could confer upon MONW individuals a type 2 diabetes mellitus and cardiovascular diseases(CVD) risk however, research on MONW is scarce. MONW individuals have metabolic disturbances typical of obese persons and are identified by having a high amount of visceral fat, a low BMI, a high fat mass, a low lean body mass, low insulin sensitivity, and high triglyceride concentrations. The purpose of this study is to review several markers as potential modulators in individuals displaying the "MONW". Body fat appears to be functionally comparable with a dynamic endocrine organ, producing and secreting various adipocy tokines, such as leptin, adiponectin, CRP, tumor necrosis factor(TNF-), interleukin(IL)-6, all of which play an important role in the onset of cardiovascular disease, and insulin resistance. Otherwise, physical activity and a lower inflammation state might be helped to reduce the number of persons at risk of diabetes, CVD complications, or premature mortality. We should provide a method to optimal treatments resolving the emerging public health problem to prevention of MONW by providing guideline for physical activity as an optimal treatment for the MONW Korean. Furthermore we expect to develop a new strategy to manage MONW Korean in this society in terms of reducing medical costs and enhancing public health care for uprising population with MONW.

• 한국식품과학회지
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• 제39권6호
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• pp.701-707
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• 2007

민간요법에서 항당뇨 및 항비만 효과가 있는 것으로 알려진 길경의 항당뇨 효과가 있는 지 여부를 in vitro에서 조사하기 위해서 길경을 70% 에탄올로 추출한 후 메탄올과 물을 섞은 용액으로 단계별로 XAD-4 column으로 분획하였다. 본 연구에서는 1) 3T3-L1 섬유아세포와 지방세포에서 길경의 추출 분획물이 인슐린처럼 작용하는 인슐린성 물질이거나, 2) 인슐린 작용을 향상시키는 인슐린 민감성 물질이거나, 또는 3) 포도당 자극에 의한 인슐린 분비를 향상시키거나, 4) 베타세포의 기능과 양을 증가시키는데 관여하는 유전자인 IRS-2, glucokinase, PDX-1의 mRNA 발현을 향상시키거나, 5) $\alpha-glucoamylase$ 활성을 억제하는 물질로 작용하는 지 여부를 조사하였다. 길경 추출 분획물은 인슐린성 물질로 작용하지 않았다. 반면에 0, 20와 100%메탄올층은 3T3-L1 지방세포에서 인슐린 자극에 의한 포도당 흡수를 증가시켰다. 이 분획층 중에서 특히 0%과 100% 메탄올 분획층은 분화 유도물질의 작용을 향상시켜 3T3-L1 섬유아세포에서 지방세포로의 분화 및 중성 지방의 축적을 증가시켰다. 그러므로 이들은 $PPAR-{\gamma}$ agonist로 작용하는 물질을 함유할 가능성이 매우 높다. 인슐린을 분비하는 세포인 Min6 세포에서 포도당 자극에 의한 인슐린 분비를 향상시키는 지 여부를 조사하였는데 20, 80 그리고 100% 메탄올층은 포도당 자극에 의한 인슐린 분비를 증가시켰다. 그 기전은 인슐린 분비와 베타세포의 증식에 관여하는 유전자의 IRS-2, glucokinase 그리고 PDX-1의 mRNA의 양을 증가시키는 것과 관련이 있다. 결론적으로 길경은 지방 세포의 분화를 촉진하는 물질, 인슐린 민감성을 향상시키는 물질 그리고 베타세포의 기능과 증식을 촉진시키는 물질을 함유하고 있으므로 우리나라 및 아시아의 사람들에서 많이 유발되는 비만을 동반하지 않은 당뇨병 및 인슐린 저항성의 치료와 예방에 중요한 역할을 할 것으로 사료된다.

• 방사선산업학회지
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• 제7권2_3호
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• pp.183-190
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• 2013

Mistletoe (Viscum album) has been widely used as a functional food material for various therapeutic purposes from ancient time. In this study, we examined anti-diabetic and cytotoxic activities of heated-treated mistletoe and the effects of gamma-irradiation on its activities. Heat-treated mistletoe extract was prepared by heating during different time (3, 6, 9 and 12 h) and gamma-irradiated with different doses of 0, 10, 30, 50, 70 and 100 kGy. Heat-treated mistletoe extracts showed a concentration-dependent cytotoxicity on rat insulinoma RINm5F cells and the effect was gradually decreased as heating time increased up to 12 h. 12 h heat-treated extract was no cytotoxic. Gamma-irradiation enhanced the reduction of heat-treated mistletoe-induced cytotoxicity and the decreasing effect was an irradiating dose-dependent. In particular, all of 70 kGy irradiated and heat-treated mistletoe extracts did not showed the cytotoxicity and the effect was comparable to 12 h heat-treated mistletoe extract. Among those extracts, 3 h heat-treated mistletoe extract gradually increased the insulin secreting activity by gamma-irradiation and the effect was the best at 70 kGy, whereas 12 heat-treated extract was no effect. On the test of ${\alpha}$-glucosidase inhibitory activity, 3 h heat-treated mistletoe extract showed the concentration dependent effects and gamma-irradiation induced more activity at 70 kGy, compared to non-irradiated 3 h and 12 h heated mistletoe extracts. These results suggest that the combination of heat treatment and gamma-irradiation might be more effective than only heat-treatment for improving the anti-diabetic activity of mistletoe extract and reducing its cytotoxicity.

• 대한의생명과학회지
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• 제20권1호
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• pp.14-24
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• 2014

Hypoxia is one of the main reasons for islet apoptosis after transplantation as well as during isolation. In this study, we attempted to determine the potential usefulness of NF-${\kappa}B$ inhibitor for suppression of hypoxia-induced ${\beta}$-cell apoptosis as well as the relationship between IP-10 induction and ${\beta}$-cell apoptosis in hypoxia. To accomplish this, we cultured the mouse pancreatic ${\beta}$-cell line MIN6 in hypoxia (1% $O_2$). Among several examined chemokines, only IP-10 mRNA expression was induced under hypoxia, and this induced IP-10 expression was due to NF-${\kappa}B$ activity. Since a previous study suggested that IP-10 mediates ${\beta}$-cell apoptosis, we measured hypoxia-induced IP-10 protein and examined the effect of anti-IP-10 neutralizing Ab on hypoxia-induced ${\beta}$-cell apoptosis. However, IP-10 protein was not detected, and anti-IP-10 neutralizing Ab did not rescue hypoxia-induced MIN6 apoptosis, indicating that there is no relationship between hypoxia-induced IP-10 mRNA expression and hypoxia-induced ${\beta}$-cell apoptosis. Since it was still not clear if NF-${\kappa}B$ functions as an apoptotic or anti-apoptotic mediator in hypoxia-induced ${\beta}$-cell apoptosis, we examined possible involvement of NF-${\kappa}B$ in hypoxia-induced ${\beta}$-cell apoptosis. Treatment with 1 ${\mu}M$ NF-${\kappa}B$ inhibitor suppressed hypoxiainduced apoptosis by more than 50%, while 10 ${\mu}M$ AP-1 or 4 ${\mu}M$ NF-AT inhibitor did not, indicating involvement of NF-${\kappa}B$ in hypoxia-induced ${\beta}$-cell apoptosis. Overall, these results suggest that IP-10 is not involved in hypoxia-induced ${\beta}$-cell apoptosis, and that NF-${\kappa}B$ inhibitor can be useful for ameliorating hypoxia-induced ${\beta}$-cell apoptosis.