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Mannogalactoglucan from mushrooms protects pancreatic islets via restoring UPR and promotes insulin secretion in TIDM mice

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Food Science and Human Wellness 2024年第3期13卷 1390-1401页

作者： Ting Liu Si Chen Yunhe Qu Lujuan Zheng Xiaoxuan Yang Shuhan Men Yuanning Wang Hanrui Ma Yifa Zhou Yuying Fan Engineering Research Center of Glycoconjugates Ministry of EducationJilin Provincial Key Laboratory of Chemistry and Biology of Changbai Mountain Natural DrugsSchool of Life SciencesNortheast Normal UniversityChangchun 130024China

Type 1 diabetes mellitus(T1DM) lacks insulin secretion due to autoimmune deficiency of pancreaticβ-*** pancreatic islets and enhancing insulin secretion has been therapeutic *** is the main type of polysaccharide from natural mushroom,which has potential medicinal ***,the antidiabetic property of mannogalactoglucan in T1DM has not been fully *** this study,we obtained the neutral fraction of alkali-soluble Armillaria mellea polysaccharide(AAMP-N) with the structure of mannogalactoglucan from the fruiting body of *** and investigated the potential therapeutic value of AAMP-N in *** demonstrated that AAMP-N lowered blood glucose and improved diabetes symptoms in T1DM ***-N activated unfolded protein response(UPR) signaling pathway to maintain ER protein folding homeostasis and promote insulin secretion in *** that,AAMP-N promoted insulin synthesis via upregulating the expression of transcription factors,increased Ca^(2+) signals to stimulate intracellular insulin secretory vesicle transport via activating calcium/calmodulin-dependent kinase Ⅱ(CamkⅡ) and cAMP/PKA signals,and enhanced insulin secretory vesicle fusion with the plasma membrane via vesicle-associated membrane protein 2(VAMP2).Collectively,these studies demonstrated that the therapeutic potential of AAMP-N on pancreatic islets function,indicating that mannogalactoglucan could be natural nutraceutical used for the treatment of T1DM.

关键词： Mannogalactoglucan Mushroom pancreatic islets Insulin secretion Insulin synthesis Unfolded protein response(UPR) Type 1 diabetes mellitus(T1DM)

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Therapeutic effects of berberine in impaired glucose tolerance rats and its influence on insulin secretion

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Acta Pharmacologica Sinica 2004年第4期25卷 98-104页

作者： San-hua LENG, Fu-er LU2, Li-jun XU Institute of Integrated Traditional Chinese & Western Medicine, Tongji Hospital, TongjiMedical College, Huazhong University of Science & Technology, Wuhan 430030, China Institute of Integrated Traditional Chinese & Western Medicine Tongji Hospital Tongji Medical College Huazhong University of Science & Technology China

AIM: To explore the anti-diabetic effects of berberine and its influence on insulin secretion. METHODS: Impaired glucose tolerance rats induced by iv injection of streptozotocin 30 mg/kgwere treated with berberine 187.5 and 562.5 mg/kg while fed with high fat laboratory chow. After rats were treated for 4 weeks, oral glucose tolerance was determined, and for 8 weeks, the fasting blood glucose, insulin, lipid series were determined. In insulin secretion experiments, berberine 93.75, 187.5, and 562.5 mg/kg was administered orally to BALB/c mice at a bolus. The murine serum was collected 2 h after the berberine administration for insulin determination. Insulin released from HIT-T15 cells and pancreatic islets incubated with berberine 1-100 μmol/L for 12 h was determined. RESULTS: The levels of fasting blood glucose (7.4±1.5 or 7.3±1.3 vs 9.3±1.3 mmol/L), triglycerides (0.61±0.22 or 0.63± 0.17 vs 1.8±0.7 mmol/L), total cholesterol (1.8±0.3 or 1.9±0.3 vs 2.2±0.2 mmol/L), free fatty acid (456±93 or 460±72 vs 550±113 μmol/L) and apolipoprotein B (0.37±0.02 or 0.42±0.05 vs 0.46±0.04 g/L) were reduced greatly in berberine-treated groups at doses of 187.5 and 562.5 mg·kg-1·d-1, respectively as compared with those in control group (Ppancreatic islets in a dose-dependent manner. Meanwhile murine serum insulin level (27.5±2.7 or 29±4 or 29±4 vs 24.3±2.8 pIU/L) was undoubtedly promoted and blood glucose (4.52±0.31 or 4.45±0.29 or 4.30±0.19 vs 4.87±0.21 mmol/L) was reduced after berberine administration at doses of 93.75, 187.5, and 562.5 mg/kg, respectively in the BALB/c mice. CONCLUSION: Berberine possesses anti-diabetic effec

关键词： berberine diabetes mellitus glucose tolerance test insulin HIT-T15 cells pancreatic islets lipids

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Testing of a New Collagenase Blend for pancreatic Islet Isolation Produced by Clostridium histolyticum

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Advances in Bioscience and Biotechnology 2018年第1期9卷 26-35页

作者： Zuzana Berková Frantisek Saudek Ivan Leontovyc Martin Benesík Dana Stveráková Laboratory of pancreatic islets Institute for Clinical and Experimental MedicinePragueCzech Republic Department of Diabetes Institute for Clinical and Experimental MedicinePragueCzech Republic MB Pharma Ltd. PragueCzech Republic

Clostridium histolyticum is used for production of several proteolytic enzymes such as elastase, neutral proteases, clostripain and in particular collagenase. Besides industrial applications, collagenase has been indispensable for medical purposes including isolation of pancreatic islets for diabetes treatment. The aim of this study was to optimize the method for production and partial purification of a new collagenase blend and to test its suitability for successful pancreatic islets isolation in a rat model. Bacterial strain of C. histolyticum was sequenced for presence of the collagenase genes. Different fermentation conditions were tested and the process of collagenase extraction was modified and optimized. Samples of collagenases were taken for western blot detection, activity assessment, and ability for dissociation of pancreatic tissue. Findings indicate that concentrated trypton growth medium with pepton was the most suitable for Clostridium growth and collagenase production. Whole genome sequencing revealed two genes for collagenase and also gene for clostripain. Western blot specific detection helped to select useful production modifications. Following these modifications was also improved the yield, morphology and in vitro function of intact pancreatic islets which were finally comparable or better than those achieved using standard blends of collagenase. The results support the use of the new collagenase blend for islet isolation giving thus the opportunity to choose an alternative product. Our next steps would lead to further enzyme purification through scaling up of the production method for a wider use.

关键词： Clostridium histolyticum Fermentation Collagenase pancreatic islets Islet Isolation

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