Effect of forty-eight-hour glucose infusion into rats on islet ion fluxes, ATP/ADP ratio and redox ratios of pyridine nucleotides

Abstract

Glucose infusion into rats has been shown to sensitize/ desensitize insulin secretion in response to glucose. In pancreatic islets from glucose-infused rats (GIR) (48 h, 50%, 2 ml/h) basal insulin release (2·8 mmol/l glucose) was more than fourfold compared with islets from salineinfused controls and the concentration-response curve for glucose was shifted to the left with a maximum at 11·1 mmol/l. The concentration-response curve for 45 Ca 2+ uptake was also shifted to the left in islets from GIR with a maximum at 11·1 mmol/l glucose. Starting from a high basal level at 2·8 mmol/l glucose KCl produced no insulin release or 45 Ca2+ uptake in islets from GIR. Islets from GIR exhibited a higher ATP/ADP ratio in the presence of 2·8 mmol/l glucose and marked inhibition of 86 Rb + efflux occurred even at 3 mmol/l glucose. Moreover, in islets from GIR the redox ratios of pyridine nucleotides were increased. On the other hand insulin content was reduced to about 20%.The data suggest that a 48-h glucose infusion sensitizes glucose-induced insulin release in vitro in concentrations below 11·1 mmol/l. This may, at least in part, be due to enhanced glucose metabolism providing increased availability of critical metabolic factors including ATP which, in turn, decrease the threshold for depolarization and therefore calcium uptake. Calcium uptake may then be further augmented by elevation of the redox state of pyridine nucleotides.

Prolonged glucose infusion into conscious rats inhibits early steps in insulin signalling and induces translocation of GLUT4 and protein kinase C in skeletal muscle

“…Furthermore, the glucose oversupply leads to enhanced glucose sensitivity of the beta cell, ie. the beta cells of glucose-infused rats show enhanced insulin secretion at lower glucose concentrations [41]. This data could explain the hyperinsulinaemia seen in GR after 5 days, in spite of normoglycaemia (Table 2).…”

“…Glucose infusion was performed as previously described [41]. Briefly, each rat was anaesthetized with an intraperitoneal injection of a mixture of Ketanest and Rompun at 45 mg/kg and 12 mg/kg, respectively.…”

“…Rats were allowed water and chow pellet ad libitum. Blood samples were taken from the tail vein and glucose and insulin concentrations were determined as previously described [41].…”

Glucose oversupply increases Δ9-desaturase expression and its metabolites in rat skeletal muscle

“…Glucose infusion was done as previously described [29]. After placing the catheter rats, were allowed to recover for 48 h, after which glucose infusion (2.77 mol/l glucose) was started at a rate of 2 ml/h (GR) compared with 77 mmol/l saline infusion at 2 ml/h (C).…”

“…Rats were allowed water and chow pellet freely. To measure plasma glucose and insulin concentrations blood samples were taken from the tail vein [29]. After day 2 or day 5 of continuous infusion rats were killed and mixed hind-limb muscles were dissected free of connective tissue and fat, cut into small pieces and subsequently stored at −80°C and subsequently analysed for glycogen and triglycerides [30].…”