In vitro exhaustion of pancreatic beta-cells.

To learn more about possible limited beta-cell secretory capacity and factors essential for insulin release, a perifusion system was applied that allowed the in vitro study of insulin secretion from isolated pancreatic islets for more than 6 h. Islets isolated from rats were stimulated with various glucose concentrations (7.5, 16.7, and 30 mM), alpha-ketoisocaproate (30 mM), and 30 mM glucose plus 1 mM 3-isobutyl-1-methylxanthine for several hours in Krebs-Ringer-bicarbonate buffer (KRB) or RPMI 1640. Islets showed "exhaustion" with all stimulatory conditions used when KRB was the perifusion medium. This was not prevented by addition of amino acids, phosphate, myo-inositol or arachidonic acid. With RPMI 1640 as the basal medium, exhaustion was not seen at 7.5 mM but was readily approached at higher glucose concentrations. It is possible that the exhaustion phenomenon observed here is due to a depletion of a readily releasable insulin pool.

[1]  F. Matschinsky,et al.  An enzymatic fluorimetric assay for myo-inositol. , 1984, Analytical biochemistry.

[2]  S. Bonner-Weir,et al.  Partial pancreatectomy in the rat and subsequent defect in glucose-induced insulin release. , 1983, The Journal of clinical investigation.

[3]  D. Greene,et al.  Sodium- and energy-dependent uptake of myo-inositol by rabbit peripheral nerve. Competitive inhibition by glucose and lack of an insulin effect. , 1982, The Journal of clinical investigation.

[4]  A. Winegrad,et al.  Significance of tissue myo-inositol concentrations in metabolic regulation in nerve. , 1982, Science.

[5]  H. Landahl,et al.  Heterogeneity and compartmental properties of insulin storage and secretion in rat islets. , 1982, The Journal of clinical investigation.

[6]  R. Clements,et al.  Myo-lnositol and the Maintenance of β-Cell Function in Cultured Rat Pancreatic Islets , 1981, Diabetes.

[7]  P. Arner,et al.  Segmental Pancreatic Transplantation with Duct Ligation or Drainage to a Jejunal Roux-en-Y Loop in Nonuremic Diabetic Patients , 1980, Diabetes.

[8]  P. Lacy,et al.  Insulin and Glucagon Secretion from Rat Islets Maintained in a Tissue Culture-Perifusion System , 1979, Diabetes.

[9]  F. Matschinsky,et al.  Alterations in pancreatic islet phosphate content during secretory stimulation with glucose. , 1979, Biochimica et biophysica acta.

[10]  M. Berridge,et al.  Inhibition of phosphatidylinositol synthesis and the inactivation of calcium entry after prolonged exposure of the blowfly salivary gland to 5-hydroxytryptamine. , 1979, The Biochemical journal.

[11]  R. C. Adelman,et al.  A possible role for insulin in the altered capability for hepatic enzyme adaptation during aging. , 1976, Biochemical and biophysical research communications.

[12]  E. Verspohl,et al.  Pyridine nucleotides in pancreatic islets during inhibition of insulin release by exogenous insulin. , 1976, Endocrinology.

[13]  N. Freinkel,et al.  Relationship between efflux of ionic calcium and phosphorus during excitation of pancreatic islets with glucose. , 1976, Biochimica et biophysica acta.

[14]  P. Lacy,et al.  Long-term Perfusion of Isolated Rats Islets in Vitro , 1976, Diabetes.

[15]  R. Clements,et al.  Phosphoinositide metabolism and insulin secretion from isolated rat pancreatic islets. , 1976, The Journal of clinical investigation.

[16]  J. Bonnar,et al.  Rapid transient efflux of phosphate ions from pancreatic islets as an early action of insulin secretagogues. , 1974, The Journal of clinical investigation.

[17]  F. Matschinsky,et al.  Glucose modulation of amino acid-induced glucagon and insulin release in the isolated perfused rat pancreas. , 1974, The Journal of clinical investigation.

[18]  E. Cerasi,et al.  Decreased Sensitivity of the Pancreatic Beta Cells to Glucose in Prediabetic and Diabetic Subjects: A Glucose Dose-Response Study , 1972, Diabetes.

[19]  R. M. Broekhuyse.  Changes in myo-inositol permeability in the lens due to cataractous conditions. , 1968, Biochimica et biophysica acta.

[20]  O. H. Lowry,et al.  QUANTITATIVE HISTOCHEMICAL ANALYSIS OF GLYCOLYTIC INTERMEDIATES AND COFACTORS WITH AN OIL WELL TECHNIQUE , 1968, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[21]  P. Lacy,et al.  Method for the Isolation of Intact Islets of Langerhans from the Rat Pancreas , 1967, Diabetes.

[22]  V. Herbert,et al.  Coated charcoal immunoassay of insulin. , 1965, The Journal of clinical endocrinology and metabolism.

[23]  F. Dohan,et al.  The production of hydropic degeneration of the islands of Langerhans by intraperitoneal glucose injections in the cat. , 1947, The American journal of the medical sciences.

[24]  F. Dohan,et al.  PITUITARY-DIABETES IN THE CAT; RECOVERY FOLLOWING INSULIN OR DIETARY TREATMENT , 1942 .