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

Aims/hypothesis. Glycaemia does not change following a 60% pancreatectomy i n rats because of enhanced beta-cell function and proliferation (so-called beta-cell adaptation). We previously studied these rats 4 weeks after surge ry and showed hypersensitization of glucose-induced insulin secretion becau se of increased glucokinase activity. In this study of 60% pancreatectomy r ats 5 days after surgery, when beta-cell proliferation increased threefold, we investigated whether increases in glucose metabolism enhance the produc tion 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 phosphor ylation increased threefold, but overall glucose usage increased only twofo ld. The glucose-6-phosphate (G6P) concentration thus doubled, resulting in a sixfold increase in G6P metabolism through the pentose phosphate shunt (P PS). The pentose phosphate shunt generates ribose-5-phosphate for nucleotid e synthesis, and DNA synthesis doubled in the partial pancreatectomy islets . In contrast, partial pancreatectomy rats 4 weeks after surgery had a smal ler increase in glucokinase activity and their islet glucose-6-phosphate co ncentration and pentose phosphate shunt activity were equal to that of the control rats. DNA synthesis and beta-cell proliferation, based on BrdU inco rporation were close to normal. Another consequence of the heightened gluco se metabolism in the 5-day partial pancreatectomy islets was twofold increa se in production of glucose-derived lipid and the amino acids, alanine and glutamate. Conclusions/interpretation. The enhanced glucokinase activity in 60% pancre atectomy rats supports the compensatory beta-cell hyperproliferation by inc reasing production of glucose-derived DNA, lipids and amino acids.