• Asian Pacific Journal of Cancer Prevention
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• 제14권10호
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• pp.5687-5692
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• 2013

Type 2 diabetes mellitus (T2DM) has contributed to advanced breast cancer development over the past decades. However, the mechanism underlying this contribution is poorly understood. In this study, we determined that high glucose enhanced proteasome activity was accompanied by enhanced proliferation, migration and invasion, as well as suppressed apoptosis, in human breast cancer MCF-7 cells. Proteasome inhibitor bortezomib (BZM) pretreatment mitigated high glucose-induced MCF-7 cell growth and invasion. Furthermore, high glucose increased protein kinase C delta ($PKC{\delta}$)-phosphorylation. Administration of the specific $PKC{\delta}$ inhibitor rottlerin attenuated high glucose-stimulated cancer cell growth and invasion. In addition, $PKC{\delta}$ inhibition by both rottlerin and $PKC{\delta}$ shRNA significantly suppressed high glucose-induced proteasome activity. Our results suggest that $PKC{\delta}$-dependent ubiquitin proteasome system activation plays an important role in high glucose-induced breast cancer cell growth and metastasis.

• Journal of Ginseng Research
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• 제46권6호
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• pp.780-789
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• 2022

Background: Incretin impairment, characterized by insufficient secretion of L-cell-derived glucagon-like peptide-1 (GLP-1), is a defining step of type 2 diabetes mellitus (T2DM). Ginsenoside compound K (CK) can stimulate GLP-1 secretion; however, the potential mechanism underlying this effect has not been established. Methods: CK (40 mg/kg) was administered orally to male db/db mice for 4 weeks. The body weight, oral glucose tolerance, GLP-1 secretion, gut microbiota sequencing, bile acid (BA) profiles, and BA synthesis markers of each subject were then analyzed. Moreover, TGR5 expression was evaluated by immunoblotting and immunofluorescence, and L-cell lineage markers involved in L-cell abundance were analyzed. Results: CK ameliorated obesity and impaired glucose tolerance in db/db mice by altering the gut microbiota, especially Ruminococcaceae family, and this changed microbe was positively correlated with secondary BA synthesis. Additionally, CK treatment resulted in the up-regulation of CYP7B1 and CYP27A1 and the down-regulation of CYP8B1, thereby shifting BA biosynthesis from the classical pathway to the alternative pathway. CK altered the BA pool by mainly increasing LCA and DCA. Furthermore, CK induced L-cell number expansion leading to enhanced GLP-1 release through TGR5 activation. These increases were supported by the upregulation of genes governing GLP-1 secretion and L-cell differentiation. Conclusions: The results indicate that CK improves glucose homeostasis by increasing L-cell numbers, which enhances GLP-1 release through a mechanism partially mediated by the gut microbiota-BA-TGR5 pathway. Therefore, that therapeutic attempts with CK might be useful for patients with T2DM.

• Journal of Ginseng Research
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• 제26권4호
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• pp.191-195
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• 2002

MLD STZ로 당뇨를 유발시킨 SD rat에서 투여 시기에 따른 백삼의 항당뇨 활성을 비교한 결과를 요약하면 다음과 같다. 1. 동시 투여군은 실험 시작 초반에 체중이 감소하는 듯 하였다가 당뇨 대조군에 비하여 현저히 체중이 증가하였고 후 투여군 역시 백삼의 투여에 의하여 체중이 증가하였다. 2. 동시 투여군에서 STZ 투여 후 초반 7일간 혈당이 상승 하였으나 곧 탁월한 혈당 강하 활성을 나타내었으며 또한 계속적:인 당뇨병의 진행을 막아주었다. 후 투여군에서는 즉각적으로 혈당 강하 활성이 나타났고 이는 투여 종료 시점까지 유지되었다. 3. 동시 투여군과 후 투여군 모두 식이량과 음용수 섭취량을 개선시켜 주었다. 4. 동시 투여군과 후 투여군은 모두 체중 대비 신장 무게의 비를 낮추어 줌으로써 고혈당으로 인해 야기되는 신장비대를 개선시켜 주었다. 5. STZ로 유도된 당뇨 흰쥐에서 백삼이 혈당 강하 활성을 나타내는 것은 췌장 베타세포의 보호 활성과 insulin의 분비 촉진과 관련이 있을 것으로 추측된다. 6. 각 투여군에서 투여 종료시점의 혈당이 당뇨 대조군에 비하여 각각 64%, 67%수준을 나타내어 백삼이 당뇨병이 발생되기 전이나 혹은 당뇨병이 발생된 후에 투여되더라도 우수한 혈당강하 효과를 나타낼 수 있음을 알 수 있었다. 따라서 인삼은 impaired glucose tolerance(IGT)를 나타내는 사람에서 당뇨병의 발병을 예방할 목적으로 투여할수 있을 뿐만 아니라 이미 당뇨병이 발병된 사람에서도 우수한 혈당 강하 활성을 나타내어 치료제로서의 가능성도 보여주었다.

• 한국발생생물학회지:발생과생식
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• 제24권3호
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• pp.231-239
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• 2020

Many benefits of silk protein fibroin (SPF) have been suggested in biomedical applications; and notably, significant SPF effects have been observed for metabolic syndromes that are directly linked to insulin resistance, such as type 2 diabetes mellitus (T2DM). Based on our previous findings, we believe that SPF from spiders exhibits outstanding glucose-lowering effects in diabetic BKS.Cg-m+/+Lepr^db mice. In order to evaluate the dietary effects of SPF in diabetic animals, we generated several lines of transgenic rice (TR) that expresses SPF, and the feeding of TR-SPF to diabetic animals decreased blood glucose levels, but did not change insulin levels. Western blot analyses of hepatic proteins showed that AMP-activated protein kinase (AMPK) expression and phosphorylation both decreased in TR-SPF-fed groups, compared with controls. This finding suggests that the glucose-lowering effects in this diabetic animal model might be AMPK-independent. In contrast, six-transmembrane protein of prostate 2 (STAMP2) was upregulated after TR-SPF exposure. Together with STAMP2, the Akt protein phosphorylation increased after TR-SPF exposure, which indicates that STAMP2 leads to Akt phosphorylation and thus increases insulin sensitivity in hepatocytes. Importantly, the hepatic steatosis that was seen in the liver of diabetic mice was remarkably alleviated in TR-SPF-fed mice. Hepatocytes that were immunopositive for STAMP2 were overwhelmingly observed in hepatic tissues from TR-SPF-fed mice compared to the control. Taken together, these results suggest that feeding diabetic mice with TR-SPF upregulates STAMP2 expression and increases Akt phosphorylation in hepatic tissues and thus potentially alleviates insulin resistance and hepatic steatosis.