Search: WFRF:(Sharoyko Vladimir) >
Inhibition of the m...
-
Stamenkovic, JelenaLund University,Lunds universitet,Diabetes - molekylär metabolism,Forskargrupper vid Lunds universitet,Diabetes - Molecular Metabolism,Lund University Research Groups
(author)
Inhibition of the malate-aspartate shuttle in mouse pancreatic islets abolishes glucagon secretion without affecting insulin secretion
- Article/chapterEnglish2015
Publisher, publication year, extent ...
Numbers
-
LIBRIS-ID:oai:lup.lub.lu.se:be6c2aba-8b8b-4b50-aad4-a22ea306509b
-
https://lup.lub.lu.se/record/7425444URI
-
https://doi.org/10.1042/BJ20140697DOI
Supplementary language notes
-
Language:English
-
Summary in:English
Part of subdatabase
Classification
-
Subject category:art swepub-publicationtype
-
Subject category:ref swepub-contenttype
Notes
-
Altered secretion of insulin as well as glucagon has been implicated in the pathogenesis of Type 2 diabetes (T2D), but the mechanisms controlling glucagon secretion from alpha-cells largely remain unresolved. Therefore, we studied the regulation of glucagon secretion from alpha TC1-6 (alpha TC1 clone 6) cells and compared it with insulin release from INS-1 832/13 cells. We found that INS-1 832/13 and alpha TC1-6 cells respectively secreted insulin and glucagon concentration-dependently in response to glucose. In contrast, tight coupling of glycolytic and mitochondrial metabolism was observed only in INS-1 832/13 cells. Although glycolytic metabolism was similar in the two cell lines, TCA (tricarboxylic acid) cycle metabolism, respiration and ATP levels were less glucose-responsive in alpha TC1-6 cells. Inhibition of the malate-aspartate shuttle, using phenyl succinate (PhS), abolished glucose-provoked ATP production and hormone secretion from alpha TC1-6 but not INS-1 832/13 cells. Blocking the malate-aspartate shuttle increased levels of glycerol 3-phosphate only in INS-1 832/13 cells. Accordingly, relative expression of constituents in the glycerol phosphate shuttle compared with malate-aspartate shuttle was lower in alpha TC1-6 cells. Our data suggest that the glycerol phosphate shuttle augments the malate-aspartate shuttle in INS-1 832/13 but not alpha TC1-6 cells. These results were confirmed in mouse islets, where PhS abrogated secretion of glucagon but not insulin. Furthermore, expression of the rate-limiting enzyme of the glycerol phosphate shuttle was higher in sorted primary beta-than in alpha-cells. Thus, suppressed glycerol phosphate shuttle activity in the alpha-cell may prevent a high rate of glycolysis and consequently glucagon secretion in response to glucose. Accordingly, pyruvate-and lactate-elicited glucagon secretion remains unaffected since their signalling is independent of mitochondrial shuttles.
Subject headings and genre
Added entries (persons, corporate bodies, meetings, titles ...)
-
Andersson, LottaLund University,Lunds universitet,Diabetes - molekylär metabolism,Forskargrupper vid Lunds universitet,Diabetes - Molecular Metabolism,Lund University Research Groups(Swepub:lu)med-laa
(author)
-
Adriaenssens, Alice E.
(author)
-
Bagge, AnnikaLund University,Lunds universitet,Diabetes - molekylär metabolism,Forskargrupper vid Lunds universitet,Diabetes - Molecular Metabolism,Lund University Research Groups(Swepub:lu)med-aib
(author)
-
Sharoyko, VladimirLund University,Lunds universitet,Institutionen för experimentell medicinsk vetenskap,Medicinska fakulteten,Department of Experimental Medical Science,Faculty of Medicine(Swepub:lu)med-vrs
(author)
-
Gribble, Fiona
(author)
-
Reimann, Frank
(author)
-
Wollheim, ClaesLund University,Lunds universitet,Genomik, diabetes och endokrinologi,Forskargrupper vid Lunds universitet,Genomics, Diabetes and Endocrinology,Lund University Research Groups,University of Geneva(Swepub:lu)med-cwe
(author)
-
Mulder, HindrikLund University,Lunds universitet,Diabetes - molekylär metabolism,Forskargrupper vid Lunds universitet,Diabetes - Molecular Metabolism,Lund University Research Groups(Swepub:lu)medk-hmu
(author)
-
Spégel, PeterLund University,Lunds universitet,Diabetes - molekylär metabolism,Forskargrupper vid Lunds universitet,Diabetes - Molecular Metabolism,Lund University Research Groups(Swepub:lu)tekn-psp
(author)
-
Diabetes - molekylär metabolismForskargrupper vid Lunds universitet
(creator_code:org_t)
Related titles
-
In:Biochemical Journal468, s. 49-630264-6021
Internet link
Find in a library
To the university's database
- By the author/editor
-
Stamenkovic, Jel ...
-
Andersson, Lotta
-
Adriaenssens, Al ...
-
Bagge, Annika
-
Sharoyko, Vladim ...
-
Gribble, Fiona
-
show more...
-
Reimann, Frank
-
Wollheim, Claes
-
Mulder, Hindrik
-
Spégel, Peter
-
show less...
- About the subject
-
- MEDICAL AND HEALTH SCIENCES
-
MEDICAL AND HEAL ...
-
and Clinical Medicin ...
-
and Endocrinology an ...
- Articles in the publication
-
Biochemical Jour ...
- By the university
-
Lund University