title: Long-term effects of a high glucose concentration in vitro on the oxidative metabolism and insulin production of isolated rat pancreatic islets.
abstract: The present study was performed to clarify whether exposure in tissue culture of pancreatic islet B cells to high glucose concentrations will lead to glucose insensitivity and/or toxicity. For this purpose, isolated rat islets were maintained in tissue culture for up to 7 days in the presence of either 5.6, 11, or 56 mmol/L glucose and subsequently analyzed with regard to oxidative metabolism, insulin release, islet content of insulin, and insulin mRNA. Islets maintained at 56 mmol/L glucose showed a decreased insulin content, but no changes in insulin mRNA content when compared with control islets (cultured at 11 mmol/L glucose). In short-term incubations of the high-glucose cultured islets, the rate of insulin release at 1.67 mmol/L glucose was enhanced and could not be further stimulated by a 16.7-mmol/L glucose challenge. However, the insulin release at 16.7 mmol/L was decreased when compared with islets cultured at 11 mmol/L glucose. Islets cultured at 56 mmol/L glucose showed an increased oxygen uptake when incubated at 1.67 mmol/L glucose with no further stimulation at 16.7 mmol/L glucose. These islets also showed increased rates of glucose oxidation at incubation with 1.67 mmol/L glucose, but similar rates of oxidation at 16.7 mmol/L glucose as compared with islets cultured in 11 mmol/L glucose. Islets cultured at 5.6 mmol/L glucose showed decreased insulin release when incubated at either 1.67 mmol/L or 16.7 mmol/L glucose. The rates of glucose oxidation of these islets were also decreased at 16.7 mmol/L glucose when compared with the controls, whereas the oxygen uptake was decreased only during incubation at 1.67 mmol/L glucose. There was also a decreased content of insulin mRNA in these islets.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Medical Cell Biology, Uppsala University, Sweden.
authors.forename: C
authors.initials: C
authors.lastname: Svensson
authors.forename: C
authors.initials: C
authors.lastname: Hellerström
mesh_terms: D000818:Animals; D046508:Culture Techniques; D005947:Glucose / Q000378:metabolism* / Q000494:pharmacology; D007328:Insulin / Q000235:genetics / Q000378:metabolism*; D007515:Islets of Langerhans / Q000378:metabolism*; D008297:Male; D009994:Osmolar Concentration; D010084:Oxidation-Reduction; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D013997:Time Factors
chemical_list: D007328:Insulin; D012333:RNA, Messenger; D005947:Glucose