The protective role of metformin in autophagic status in peripheral blood mononuclear cells of type 2 diabetic patients.
Identifieur interne : 000026 ( Main/Exploration ); précédent : 000025; suivant : 000027The protective role of metformin in autophagic status in peripheral blood mononuclear cells of type 2 diabetic patients.
Auteurs : Debalina Bhattacharya [Inde] ; Moumita Dutta [Inde] ; Mainak Mukhopadhyay [Inde] ; Maitree Bhattacharyya [Inde] ; Subhankar Chowdhury [Inde] ; Parimal Karmakar [Inde]Source :
- Cell biology international [ 1095-8355 ] ; 2020.
Abstract
Autophagy plays an important role in the pathophysiology of type 2 diabetes (T2D). Metformin is the most common antidiabetic drug. The main objective of this study was to explore the molecular mechanism of metformin in starvation-induced autophagy in peripheral blood mononuclear cells (PBMCs) of type 2 diabetic patients. PBMCs were isolated from 10 diabetic patients and 7 non-diabetic healthy volunteers. The autophagic puncta and markers were measured with the help of monodansylcadaverine staining and western blot. Additionally, transmission electron microscopy was also performed. No significant changes were observed in the initial autophagy marker protein levels in PBMCs of T2D after metformin treatment though diabetic PBMCs showed a high level of phospho-mammalian target of rapamycin, p62 and reduced expression of phospho-AMP-activated protein kinase and lysosomal membrane-associated protein 2, indicating a defect in autophagy. Also, induction of autophagy by tunicamycin resulted in apoptosis in diabetic PBMCs as observed by caspase-3 cleavage and reduced expression of Bcl2. Inhibition of autophagy by bafilomycin rendered consistent expression of p62 indicating a defect in the final process of autophagy. Further, electron microscopic studies also confirmed massive vacuole overload and a sign of apoptotic cell death in PBMCs of diabetic patients, whereas metformin treatment reduced the number of autophagic vacuoles perhaps by lysosomal fusion. Thus, our results indicate that defective autophagy in T2D is associated with the fusion process of lysosomes which could be overcome by metformin.
DOI: 10.1002/cbin.11355
PubMed: 32237184
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type="wicri:Area/Main/Exploration">000095</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">The protective role of metformin in autophagic status in peripheral blood mononuclear cells of type 2 diabetic patients.</title><author><name sortKey="Bhattacharya, Debalina" sort="Bhattacharya, Debalina" uniqKey="Bhattacharya D" first="Debalina" last="Bhattacharya">Debalina Bhattacharya</name><affiliation wicri:level="1"><nlm:affiliation>Department of Microbiology, Maulana Azad College, Kolkata, West Bengal, India.</nlm:affiliation><country xml:lang="fr">Inde</country><wicri:regionArea>Department of Microbiology, Maulana Azad College, Kolkata, West Bengal</wicri:regionArea><wicri:noRegion>West Bengal</wicri:noRegion></affiliation></author><author><name sortKey="Dutta, Moumita" sort="Dutta, Moumita" uniqKey="Dutta M" first="Moumita" last="Dutta">Moumita Dutta</name><affiliation wicri:level="1"><nlm:affiliation>Division of Electron Microscopy, ICMR-NICED, Kolkata, West Bengal, India.</nlm:affiliation><country xml:lang="fr">Inde</country><wicri:regionArea>Division of Electron Microscopy, ICMR-NICED, Kolkata, West Bengal</wicri:regionArea><wicri:noRegion>West Bengal</wicri:noRegion></affiliation></author><author><name sortKey="Mukhopadhyay, Mainak" sort="Mukhopadhyay, Mainak" uniqKey="Mukhopadhyay M" first="Mainak" last="Mukhopadhyay">Mainak Mukhopadhyay</name><affiliation wicri:level="1"><nlm:affiliation>Department of Biotechnology, JIS University, Agarpara, Kolkata, West Bengal, India.</nlm:affiliation><country xml:lang="fr">Inde</country><wicri:regionArea>Department of Biotechnology, JIS University, Agarpara, Kolkata, West Bengal</wicri:regionArea><wicri:noRegion>West Bengal</wicri:noRegion></affiliation></author><author><name sortKey="Bhattacharyya, Maitree" sort="Bhattacharyya, Maitree" uniqKey="Bhattacharyya M" first="Maitree" last="Bhattacharyya">Maitree Bhattacharyya</name><affiliation wicri:level="1"><nlm:affiliation>Department of Biochemistry, University of Calcutta, Kolkata, West Bengal, India.</nlm:affiliation><country xml:lang="fr">Inde</country><wicri:regionArea>Department of Biochemistry, University of Calcutta, Kolkata, West Bengal</wicri:regionArea><wicri:noRegion>West Bengal</wicri:noRegion></affiliation></author><author><name sortKey="Chowdhury, Subhankar" sort="Chowdhury, Subhankar" uniqKey="Chowdhury S" first="Subhankar" last="Chowdhury">Subhankar Chowdhury</name><affiliation wicri:level="1"><nlm:affiliation>Department of Endocrinology & Metabolism, Institute of Postgraduate Medical Education and Research, Kolkata, West Bengal, India.</nlm:affiliation><country xml:lang="fr">Inde</country><wicri:regionArea>Department of Endocrinology & Metabolism, Institute of Postgraduate Medical Education and Research, Kolkata, West Bengal</wicri:regionArea><wicri:noRegion>West Bengal</wicri:noRegion></affiliation></author><author><name sortKey="Karmakar, Parimal" sort="Karmakar, Parimal" uniqKey="Karmakar P" first="Parimal" last="Karmakar">Parimal Karmakar</name><affiliation wicri:level="1"><nlm:affiliation>Department of Life Science and Biotechnology, Jadavpur University, Kolkata, West Bengal, India.</nlm:affiliation><country xml:lang="fr">Inde</country><wicri:regionArea>Department of Life Science and Biotechnology, Jadavpur University, Kolkata, West Bengal</wicri:regionArea><wicri:noRegion>West Bengal</wicri:noRegion></affiliation></author></analytic><series><title level="j">Cell biology international</title><idno type="eISSN">1095-8355</idno><imprint><date when="2020" type="published">2020</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Autophagy plays an important role in the pathophysiology of type 2 diabetes (T2D). Metformin is the most common antidiabetic drug. The main objective of this study was to explore the molecular mechanism of metformin in starvation-induced autophagy in peripheral blood mononuclear cells (PBMCs) of type 2 diabetic patients. PBMCs were isolated from 10 diabetic patients and 7 non-diabetic healthy volunteers. The autophagic puncta and markers were measured with the help of monodansylcadaverine staining and western blot. Additionally, transmission electron microscopy was also performed. No significant changes were observed in the initial autophagy marker protein levels in PBMCs of T2D after metformin treatment though diabetic PBMCs showed a high level of phospho-mammalian target of rapamycin, p62 and reduced expression of phospho-AMP-activated protein kinase and lysosomal membrane-associated protein 2, indicating a defect in autophagy. Also, induction of autophagy by tunicamycin resulted in apoptosis in diabetic PBMCs as observed by caspase-3 cleavage and reduced expression of Bcl2. Inhibition of autophagy by bafilomycin rendered consistent expression of p62 indicating a defect in the final process of autophagy. Further, electron microscopic studies also confirmed massive vacuole overload and a sign of apoptotic cell death in PBMCs of diabetic patients, whereas metformin treatment reduced the number of autophagic vacuoles perhaps by lysosomal fusion. Thus, our results indicate that defective autophagy in T2D is associated with the fusion process of lysosomes which could be overcome by metformin.</div></front></TEI><pubmed><MedlineCitation Status="In-Process" Owner="NLM"><PMID Version="1">32237184</PMID><DateRevised><Year>2020</Year><Month>07</Month><Day>17</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1095-8355</ISSN><JournalIssue CitedMedium="Internet"><Volume>44</Volume><Issue>8</Issue><PubDate><Year>2020</Year><Month>Aug</Month></PubDate></JournalIssue><Title>Cell biology international</Title><ISOAbbreviation>Cell Biol Int</ISOAbbreviation></Journal><ArticleTitle>The protective role of metformin in autophagic status in peripheral blood mononuclear cells of type 2 diabetic patients.</ArticleTitle><Pagination><MedlinePgn>1628-1639</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1002/cbin.11355</ELocationID><Abstract><AbstractText>Autophagy plays an important role in the pathophysiology of type 2 diabetes (T2D). Metformin is the most common antidiabetic drug. The main objective of this study was to explore the molecular mechanism of metformin in starvation-induced autophagy in peripheral blood mononuclear cells (PBMCs) of type 2 diabetic patients. PBMCs were isolated from 10 diabetic patients and 7 non-diabetic healthy volunteers. The autophagic puncta and markers were measured with the help of monodansylcadaverine staining and western blot. Additionally, transmission electron microscopy was also performed. No significant changes were observed in the initial autophagy marker protein levels in PBMCs of T2D after metformin treatment though diabetic PBMCs showed a high level of phospho-mammalian target of rapamycin, p62 and reduced expression of phospho-AMP-activated protein kinase and lysosomal membrane-associated protein 2, indicating a defect in autophagy. Also, induction of autophagy by tunicamycin resulted in apoptosis in diabetic PBMCs as observed by caspase-3 cleavage and reduced expression of Bcl2. Inhibition of autophagy by bafilomycin rendered consistent expression of p62 indicating a defect in the final process of autophagy. Further, electron microscopic studies also confirmed massive vacuole overload and a sign of apoptotic cell death in PBMCs of diabetic patients, whereas metformin treatment reduced the number of autophagic vacuoles perhaps by lysosomal fusion. Thus, our results indicate that defective autophagy in T2D is associated with the fusion process of lysosomes which could be overcome by metformin.</AbstractText><CopyrightInformation>© 2020 International Federation for Cell Biology.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Bhattacharya</LastName><ForeName>Debalina</ForeName><Initials>D</Initials><AffiliationInfo><Affiliation>Department of Microbiology, Maulana Azad College, Kolkata, West Bengal, India.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Dutta</LastName><ForeName>Moumita</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Division of Electron Microscopy, ICMR-NICED, Kolkata, West Bengal, India.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Mukhopadhyay</LastName><ForeName>Mainak</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Department of Biotechnology, JIS University, Agarpara, Kolkata, West Bengal, India.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Bhattacharyya</LastName><ForeName>Maitree</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Department of Biochemistry, University of Calcutta, Kolkata, West Bengal, India.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Chowdhury</LastName><ForeName>Subhankar</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>Department of Endocrinology & Metabolism, Institute of Postgraduate Medical Education and Research, Kolkata, West Bengal, India.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Karmakar</LastName><ForeName>Parimal</ForeName><Initials>P</Initials><AffiliationInfo><Affiliation>Department of Life Science and Biotechnology, Jadavpur University, Kolkata, West Bengal, India.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><GrantList CompleteYN="Y"><Grant><GrantID>BL/14-15/0033</GrantID><Agency>University Grants Commission</Agency><Country></Country></Grant></GrantList><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2020</Year><Month>04</Month><Day>18</Day></ArticleDate></Article><MedlineJournalInfo><Country>England</Country><MedlineTA>Cell Biol Int</MedlineTA><NlmUniqueID>9307129</NlmUniqueID><ISSNLinking>1065-6995</ISSNLinking></MedlineJournalInfo><CitationSubset>IM</CitationSubset><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">autophagy</Keyword><Keyword MajorTopicYN="N">lysosomal fusion</Keyword><Keyword MajorTopicYN="N">starvation</Keyword><Keyword MajorTopicYN="N">transmission electron microscopy</Keyword><Keyword MajorTopicYN="N">tunicamycin</Keyword></KeywordList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2019</Year><Month>10</Month><Day>31</Day></PubMedPubDate><PubMedPubDate PubStatus="revised"><Year>2020</Year><Month>03</Month><Day>20</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2020</Year><Month>03</Month><Day>29</Day></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2020</Year><Month>4</Month><Day>3</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2020</Year><Month>4</Month><Day>3</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2020</Year><Month>4</Month><Day>3</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">32237184</ArticleId><ArticleId IdType="doi">10.1002/cbin.11355</ArticleId></ArticleIdList><ReferenceList><Title>REFERENCES</Title><Reference><Citation>Alberti, K. 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