Increased islet DNA synthesis and glucose-derived lipid and amino acid production in association with beta-cell hyperproliferation in normoglycaemic 60 % pancreatectomy rats.
OBJECTIVE
Glycaemia does not change following a 60 % pancreatectomy in rats because of enhanced beta-cell function and proliferation (so-called beta-cell adaptation). We previously studied these rats 4 weeks after surgery and showed hypersensitization of glucose-induced insulin secretion because of increased glucokinase activity. In this study of 60 % pancreatectomy rats 5 days after surgery, when beta-cell proliferation increased threefold, we investigated whether increases in glucose metabolism enhance the production of glucose-derived lipid, amino acids and DNA.


METHODS
Isolated islets from 60 % pancreatectomy and sham-operated control rats 5 days or 4 weeks after surgery were studied.


RESULTS
Five days after 60 % pancreatectomy surgery, islet glucose phosphorylation increased threefold, but overall glucose usage increased only twofold. The glucose-6-phosphate (G6P) concentration thus doubled, resulting in a sixfold increase in G6P metabolism through the pentose phosphate shunt (PPS). The pentose phosphate shunt generates ribose-5-phosphate for nucleotide synthesis, and DNA synthesis doubled in the partial pancreatectomy islets. In contrast, partial pancreatectomy rats 4 weeks after surgery had a smaller increase in glucokinase activity and their islet glucose-6-phosphate concentration and pentose phosphate shunt activity were equal to that of the control rats. DNA synthesis and beta-cell proliferation, based on BrdU incorporation were close to normal. Another consequence of the heightened glucose metabolism in the 5-day partial pancreatectomy islets was twofold increase in production of glucose-derived lipid and the amino acids, alanine and glutamate.


CONCLUSIONS
The enhanced glucokinase activity in 60 % pancreatectomy rats supports the compensatory beta-cell hyperproliferation by increasing production of glucose-derived DNA, lipids and amino acids.
Liu
Y Q
YQ
Division of Endocrinology, Diabetes and Metabolism, University of Vermont College of Medicine, Burlington, Vermont, USA.
Montanya
E
E
Leahy
J L
JL
D000409:Alanine / Q000096:biosynthesis; D000596:Amino Acids / Q000096:biosynthesis*; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D002455:Cell Division; D002950:Citrate (si)-Synthase / Q000378:metabolism; D004247:DNA / Q000096:biosynthesis*; D005941:Glucokinase / Q000378:metabolism; D005947:Glucose / Q000378:metabolism*; D019298:Glucose-6-Phosphate / Q000378:metabolism; D018698:Glutamic Acid / Q000096:biosynthesis; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000166:cytology / Q000378:metabolism*; D007700:Kinetics; D008055:Lipids / Q000096:biosynthesis*; D010180:Pancreatectomy; D010427:Pentose Phosphate Pathway; D010732:Phosphofructokinase-1 / Q000378:metabolism; D010766:Phosphorylation; D051381:Rats
D000596:Amino Acids; D001786:Blood Glucose; D007328:Insulin; D008055:Lipids; D018698:Glutamic Acid; D019298:Glucose-6-Phosphate; D004247:DNA; D002950:Citrate (si)-Synthase; D010732:Phosphofructokinase-1; D005941:Glucokinase; D005947:Glucose; D000409:Alanine