Lack of long-term beta-cell glucotoxicity in vitro in pancreatic islets isolated from two mouse strains (C57BL/6J; C57BL/KsJ) with different sensitivities of the beta-cells to hyperglycaemia in vivo.
Previous studies have shown that 4 weeks after syngeneic transplantation of a suboptimal number of islets into either C57BL/6J (BL/6J) or C57BL/KsJ (BL/KsJ) diabetic mice there is an impaired insulin secretion by the perfused grafts. After normalization of the blood glucose level with a second islet graft, the BL/6J strain showed restored insulin secretion whilst that of the BL/KsJ strain remained impaired. The aim of the present work was to study the effects of glucose on the in-vitro function of islet beta-cells from these two mouse strains, with different sensitivities of their beta-cells to glucose in vivo. Isolated pancreatic islets from each strain were kept for 1 week in tissue culture at 5.6, 11, 28 or 56 mmol glucose/l and were subsequently analysed with regard to insulin release, (pro)-insulin and total protein biosynthesis, insulin, DNA and insulin mRNA contents and glucose metabolism. Islets from both strains cultured at 28 or 56 mmol glucose/l showed an increased accumulation of insulin in the culture medium and an enhanced glucose-stimulated insulin release compared with corresponding control islets cultured at 11 mmol glucose/l. After culture at either 5.6 or 56 mmol/l, rates of (pro)insulin biosynthesis were decreased in BL/KsJ islets in short-term incubations at 17 mmol glucose/l, whereas islets cultured at 56 mmol glucose/l showed a marked increase at 1.7 mmol glucose/l. In BL/6J islets, the (pro)insulin biosynthesis rates were similar to those of the BL/KsJ islets with one exception, namely that no decrease was observed at 56 mmol glucose/l. Islets of both strains showed a decreased insulin content after culture with 56 mmol glucose/l.(ABSTRACT TRUNCATED AT 250 WORDS)
Svensson
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Department of Medical Cell Biology, Uppsala University, Sweden.
Sandler
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Hellerström
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D000818:Animals; D002478:Cells, Cultured; D004247:DNA / Q000032:analysis; D005947:Glucose / Q000378:metabolism* / Q000494:pharmacology; D006943:Hyperglycemia / Q000378:metabolism*; D015151:Immunoblotting; D007328:Insulin / Q000096:biosynthesis / Q000235:genetics; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D011384:Proinsulin / Q000096:biosynthesis; D012333:RNA, Messenger / Q000032:analysis
D007328:Insulin; D012333:RNA, Messenger; D004247:DNA; D011384:Proinsulin; D005947:Glucose