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PMID:15507531
| Citation |
Liu, YQ, Han, J, Epstein, PN and Long, YS (2005) Enhanced rat beta-cell proliferation in 60% pancreatectomized islets by increased glucose metabolic flux through pyruvate carboxylase pathway. Am. J. Physiol. Endocrinol. Metab. 288:E471-8 |
|---|---|
| Abstract |
Islet beta-cell proliferation is a very important component of beta-cell adaptation to insulin resistance and prevention of type 2 diabetes mellitus. However, we know little about the mechanisms of beta-cell proliferation. We now investigate the relationship between pyruvate carboxylase (PC) pathway activity and islet cell proliferation 5 days after 60% pancreatectomy (Px). Islet cell number, protein, and DNA content, indicators of beta-cell proliferation, were increased two- to threefold 5 days after Px. PC and pyruvate dehydrogenase (PDH) activities increased only approximately 1.3-fold; however, islet pyruvate content and malate release from isolated islet mitochondria were approximately threefold increased in Px islets. The latter is an indicator of pyruvate-malate cycle activity, indicating that most of the increased pyruvate was converted to oxaloacetate (OAA) through the PC pathway. The contents of OAA and malate, intermediates of the pyruvate-malate cycle, were also increased threefold. PDH and citrate content were only slightly increased. Importantly, the changes in cell proliferation parameters, glucose utilization, and oxidation and malate release were partially blocked by in vivo treatment with the PC inhibitor phenylacetic acid. Our results suggest that enhanced PC pathway in Px islets may have an important role in islet cell proliferation. |
| Links |
PubMed Online version:10.1152/ajpendo.00427.2004 |
| Keywords |
Animals; Antimetabolites, Antineoplastic/pharmacology; Cell Count; Cell Proliferation/drug effects; Citric Acid/metabolism; DNA/analysis; DNA/metabolism; Glucose/metabolism; Islets of Langerhans/cytology; Islets of Langerhans/drug effects; Islets of Langerhans/metabolism; Malates/metabolism; Male; Mitochondria/drug effects; Mitochondria/metabolism; Models, Biological; Oxaloacetate/metabolism; Oxidation-Reduction/drug effects; Pancreatectomy; Phenylacetates/pharmacology; Proteins/analysis; Proteins/metabolism; Pyruvate Carboxylase/analysis; Pyruvate Carboxylase/metabolism; Pyruvate Dehydrogenase Complex/metabolism; Pyruvic Acid/metabolism; Rats; Rats, Sprague-Dawley; Streptavidin/chemistry |
| edit table |
Significance
Annotations
| Gene product | Qualifier | GO Term | Evidence Code | with/from | Aspect | Extension | Notes | Status |
|---|---|---|---|---|---|---|---|---|
|
enables |
GO:0004736: pyruvate carboxylase activity |
ECO:0000314: direct assay evidence used in manual assertion |
F |
Seeded From UniProt |
complete | |||
|
enables |
GO:0005524: ATP binding |
ECO:0000314: direct assay evidence used in manual assertion |
F |
Seeded From UniProt |
complete | |||
|
involved_in |
GO:0006090: pyruvate metabolic process |
ECO:0000314: direct assay evidence used in manual assertion |
P |
Seeded From UniProt |
complete | |||
|
involved_in |
GO:0006107: oxaloacetate metabolic process |
ECO:0000314: direct assay evidence used in manual assertion |
P |
Seeded From UniProt |
complete | |||
|
enables |
GO:0031406: carboxylic acid binding |
ECO:0000314: direct assay evidence used in manual assertion |
F |
Seeded From UniProt |
complete | |||
See also
References
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