Reduced glutamate decarboxylase activity in rat islet β cells which survived streptozotocin-induced cytotoxicity

AbstractRat pancreatic β cells exhibit a 16-fold higher glutamate decarboxylase (GAD) activity than islet non-β cells, but a similar glutamate dehydrogenase (GDH) activity, β Cells which survive exposure to 2 mM streptozotocin only contain 10 percent of the GAD activity of control cells, but their GDH activity remains unaltered. Culture of streptozotocin-treated β cell preparations with 2 mM nicotinamide reduces the number of dead cells and prevents in part the decline in GAD activity of surviving β cells. These data indicate that loss in activity of the β cell specific enzyme GAD can serve as marker for β cells which survived a destructive process. It is furthermore demonstrated that nicotinamide increases the percent surviving cells and decreases their loss in GAD activity

Metabolism of glycerol-1,2,3-trimethylsuccinate in rat pancreatic islets

SCOPUS: ar.jinfo:eu-repo/semantics/publishe

The stimulus-secretion coupling of amino acid-induced insulin release: insulinotropic action of branched-chain amino acids at physiological concentrations of glucose and glutamine

SCOPUS: ar.jFLWNAinfo:eu-repo/semantics/publishe

Metabolism of d-glucose and its pentaacetate ester in muscles and pancreatic islets of GLUT4 null mice.

The metabolism of d-glucose and its pentaacetate ester was investigated in GLUT4 null mice and control C57Bl6/CBA mice. The incorporation of d-[U-(14)C]glucose (1.7 mM) into glycogen of diaphragm, soleus, and extensor digitorium longus muscles averaged, in the GLUT4 null mice, only 34 +/- 7% of the mean corresponding control values. The utilization of d-[5-(3)H]glucose and conversion of d-[U-(14)C]glucose to (14)CO(2) and radioactive acidic metabolites or amino acids were little affected, however, in the muscles from GLUT4 null mice. Likewise, under steady-state conditions, the intracellular pool of 6-deoxy-6-iodo-d-glucose (10 microM) was not significantly different in muscles from GLUT4 null and control mice. The incorporation of d-[U-(14)C]glucose pentaacetate (1.7 mM) into glycogen and utilization of d-[5-(3)H]glucose pentaacetate were also not significantly different in muscles from GLUT4 null and control animals. They were about 10-30 times lower than the corresponding values found with the unesterified hexose. In pancreatic islets, however, the metabolism of d-glucose pentaacetate was not lower than that of unesterified d-glucose. Moreover, the utilization of d-[5-(3)H]glucose and catabolism of d-[U-(14)C]glucose were significantly higher in the islets from GLUT4 null mice than in those from control animals. These findings indicate that the defect of d-glucose metabolism in GLUT4 null mice occurs in muscles but not in pancreatic islets, affects preferentially glycogen synthesis rather than glycolysis, and can be bypassed by using the pentaacetate ester of the hexose. The present data also reveal a striking difference between muscles and islets when comparing the metabolism of d-glucose to that of its ester.Journal ArticleResearch Support, Non-U.S. Gov'tinfo:eu-repo/semantics/publishe

Heterogeneous secretion of individual B cells in response to D-glucose and to nonglucidic nutrient secretagogues.

We used a hemolytic plaque assay for insulin to determine whether the same pancreatic B cells respond to D-glucose, 2-amino-bicyclo[2,2,1]heptane-2-carboxylic acid (BCH) and the association of this nonmetabolized analogue of L-leucine with either the monomethyl ester of succinic acid (SME) or the dimethyl ester of L-glutamic acid (GME). During a 30-min incubation in the absence of D-glucose, BCH alone (5 mM) had no effect on insulin release. In contrast, the combination of BCH with either SME (10 mM) or GME (3 mM) stimulated insulin release to the same extent observed in the sole presence of 16.7 mM D-glucose. The effects of BCH plus SME and BCH plus GME on both percentage of secreting B cells and total insulin output were little affected in the presence of D-glucose concentrations ranging from 0 to 16.7 mM. Varying the concentration of SME from 2 to 10 mM also did not influence these effects. In other experiments, the very same B cells were first exposed 45 min to 16.7 mM D-glucose, then incubated 45 min in the presence of only BCH and SME. Under these conditions, most (80.3 +/- 2.5%) of the cells contributing to insulin release did so during both incubation periods. Furthermore, virtually all cells responding to BCH and SME during the second incubation corresponded to cells also responsive to D-glucose during the first incubation. Similar observations were made when the sequence of the two incubations was reversed.(ABSTRACT TRUNCATED AT 250 WORDS

Dynamics of insulin release and microtubular-microfilamentous system. II. Effect of vincristine.

In order to document the participation of microtubules in the dynamics of insulin release, the secretory response of the isolated perfused rat pancreas was measured after various times of exposure to vincristine (2.10-5M). After a short exposure time (25 min), both phases of glucose-induced insulin release were increased. After longer pretreatment (60 min), this facilitating effect disappeared and a slight, insignificant reduction of both phases of the secretory response to glucose was observed. A still longer exposure time (120 min) provoked a more marked and significant inhibition of the early and late phases of insulin release. The same enhancing effect after short pretreatment with vincristine was noticed when gliclazide was used as the insulinotropic agent. The ultrastructural studies indicated a progressive disappearance of microtubules concomitantly with an increase in number and size of vincristine-induced paracrystalline deposits. These findings suggest that microtubules indeed participate in the dynamics of insulin release, a reduction of both phases of insulin secretion being caused by an extended disruption of the microtubular apparatus, whereas a more limited disturbance of the microtubular system appears to be associated with facilitated insulin release in response to either glucose or sulfonylurea. © 1974 Springer-Verlag.In VitroJournal ArticleSCOPUS: ar.jinfo:eu-repo/semantics/publishe