• Title/Summary/Keyword: Insulin secreting activity

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Lithium and exercise ameliorate insulin-deficient hyperglycemia by independently attenuating pancreatic α-cell mass and hepatic gluconeogenesis

  • Su-Ryun Jung;Ji-Hye Lee;Hanguk Ryu;Yurong Gao;Jaemin Lee
    • The Korean Journal of Physiology and Pharmacology
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    • v.28 no.1
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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.

Metabolically Obese Normal Weight (MONW) (정상체중 대사비만)

  • Kang, Hyun-Joo
    • Korean Journal of Health Education and Promotion
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    • v.26 no.2
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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.

In vitro Anti-diabetic Effects of Crude Extracts of Platycodi Radix (In vitro에서 길경 추출 분획물의 항당뇨 효과 조사)

  • Ko, Byoung-Seob;Kwon, Dae-Young;Hong, Sang-Mee;Park, Sun-Min
    • Korean Journal of Food Science and Technology
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    • v.39 no.6
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    • pp.701-707
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    • 2007
  • Anti-diabetic effect of Platycodi radix (PR) extract fractions was determined if vitro by investigating insulin-like action, insulin sensitizing action, glucose-stimulated insulin secretion, gene expression related to ${\beta}-cell$ function and mass, and ${\alpha}$-glucoamylase suppressing action. Insulin-like activity was not promoted by the treatment of PR methanol factions in 373-L1 fibroblast. However, treatment with 0, 20 and 100% PR methanol fractions along with 1 ng/mL insulin increased insulin-stimulated glucose uptake in 373-L1 adipocytes. In addition, the treatment of 0% and 100% methanol fractions along with differentiation inducers significantly increased the differentiation of 373-L1 fibroblasts to adipocytes. These fractions may contain insulin sensitizer. The 20%, 80% and 100% methanol fractions enhanced glucose-stimulated insulin secretion in Min6 cells, insulin secreting cell line. This was related to the mechanism to promote glucose sensing and ${\beta}-cell$ proliferation, which was regulated by the induction of IRS-2, glucokinase and PDX-1 genes. As expected, 20, 80 and 100% methanol fractions increased mRNA levels of IRS-2, glucokinase and PDX-1 genes. However, PR fractions did not affect the ${\alpha}-glucoamylase$ activity in vitro. These data suggested that PR extract fractions have anti-diabetic actions through improving insulin sensitization, glucose-stimulated insulin secretion, and ${\beta}-cell$ proliferation. Therefore, PR extracts can be beneficial for anti-diabetic treatment in lean diabetic patients.

Effects of Gamma-irradiation on Anti-diabetic and Cytotoxic Activities of Heat-treated Mistletoe (Viscum album) (감마선 조사가 열처리 겨우살이의 항당뇨 및 세포독성에 미치는 영향)

  • Park, Jong-Heum;Kim, Su-Min;Sung, Nak-Yun;Song, Du-Sup;Byun, Eui-Baek;Kim, Jae-Kyung;Song, Beom-Seok;Lee, Ju-Woon;Kim, Jae-Hun
    • Journal of Radiation Industry
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    • v.7 no.2_3
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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.

NF-${\kappa}B$ Inhibitor Suppresses Hypoxia-induced Apoptosis of Mouse Pancreatic ${\beta}$-cell Line MIN6

  • Koh, Hyun Sook;Kim, Jae Young
    • Biomedical Science Letters
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    • v.20 no.1
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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.