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Diabetologia. 2001 Aug;44(8):1026-33.

Increased islet DNA synthesis and glucose-derived lipid and amino acid production in association with beta-cell hyperproliferation in normoglycaemic 60 % pancreatectomy rats.

Author information

1
Division of Endocrinology, Diabetes and Metabolism, University of Vermont College of Medicine, Burlington, Vermont, USA.

Abstract

AIMS/HYPOTHESIS:

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/INTERPRETATION:

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.

PMID:
11484081
DOI:
10.1007/s001250100597
[Indexed for MEDLINE]

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