Ontogeny of pyruvate dehydrogenase complex and key enzymes involved in glycolysis and tricarboxylic acid cycle in rabbit fetal lung, heart, and liver

Bhavnani, Bhagu R.; Wallace, Duncan G.

doi:10.1139/o90-179

Cited by 1 publication

(1 citation statement)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…33 PDC is, however, expressed in several tissues from late gestation. 34 During development of the pancreas in utero, new islets are generated from progenitor endocrine cells located behind the tips of the pancreatic ductal tree within the pancreatic ductal epithelium. 35 However, postnatally the pancreatic ducts cease to be a source of new islets within the rodent pancreas, and new b-cells arise for the expansion of b-cell mass by proliferation of existing cells within the islets or by the differentiation of resident islet endocrine progenitors.…”

Section: Discussionmentioning

confidence: 99%

Featured Article: Beta cell specific pyruvate dehydrogenase alpha gene deletion results in a reduced islet number and β-cell mass postnatally

Patel

Srinivasan

Strutt

et al. 2014

Exp Biol Med (Maywood)

View full text Add to dashboard Cite

The ability of pancreatic β-cells to undertake glucose-stimulated insulin secretion (GSIS) depends on the generation of adenosine triphosphate (ATP) within the mitochondria from pyruvate, a major rate-limiting enzyme being pyruvate dehydrogenase (PDH) complex (PDC). However, glucose metabolism also controls β-cell mass. To examine the role of PDC in the regulation of pancreatic β-cell development and maturation, we generated β-cell-targeted PDHα subunit knock-out male mice (β-PDHKO) and compared these with control males (β-PDHCT) from birth until 6-8 weeks age. Pancreas morphology, transcription factor expression, pancreatic insulin content, and circulating glucose and insulin values were compared. Compared to β-PDHCT male mice, β-PDHKO animals had significantly reduced pancreatic insulin content from birth, a lower serum insulin content from day 15, and relative hyperglycemia from day 30. Isolated islets from β-PDHKO mice demonstrated a reduced GSIS. The number of islets per pancreatic area, mean islet area, and the proportion of islet cells that were β-cells were all reduced in β-PDHKO animals. Similarly the number of insulin-immunopositive, extra-islet small endocrine cell clusters, a possible source of β-cell progenitors, was lower in β-PDHKO mice. Analysis of pancreatic expression of transcription factors responsible for β-cell lineage commitment, proliferation, and maturation, Pdx1, Neurogenin3, and NeuroD1 showed that mRNA abundance was reduced in the β-PDHKO. This demonstrates that PDC is not only required for insulin expression and glucose-stimulated secretion, but also directly influences β-cell growth and maturity, and positions glucose metabolism as a direct regulator of β-cell mass and plasticity.

show abstract

Section: Discussionmentioning

confidence: 99%