Search PubMed⌕ Search

Biomedical subjects

G Gold

Publications and source records attributed to G Gold.

At least 73 records · Page 4Linked to original sources
PubMed1984

Effects of monensin on conversion of proinsulin to insulin and secretion of newly synthesized insulin in isolated rat islets.

When isolated rat islets were incubated with 10(-10) - 10(-6) M monensin, a sodium and proton ionophore, glucose-stimulated insulin release was inhibited in a concentration- and time-dependent manner. After removal of monensin, inhibition of insulin secretion persisted during stimulation with a variety of secretagogues, including 5 mM glucose plus 15 mM arginine, 20 mM glucose, and 20 mM glucose plus 1 mM 3-isobutyl-1-methylxanthine. Within the same low range of monensin concentrations, proteolytic conversion of newly synthesized proinsulin to insulin was also blocked. At each concentration, prohormone-to-hormone conversion was inhibited to almost the same extent as inhibition of insulin secretion. Therefore, both processes may have equal or common dependency on a subcellular ionic gradient. Although monensin decreased total insulin secretion, the glucose-regulated marking process was unaffected. Regardless of the monensin concentration or the overall rate of insulin secretion, the percentage of secreted newly synthesized versus older insulin remained the same, and the threefold differences in the fractional secretory rates of newly synthesized versus total insulin also remained the same. Thus, rather than specifically blocking protein traffic through the Golgi apparatus of the beta cell, monensin probably first inhibited insulin secretion by disrupting proton gradients in secretory vesicles and, thereby, also inhibited other processes occurring within this organelle.

1-Methyl-3-isobutylxanthine↗
PubMed1984

Contrasting patterns of insulin biosynthesis, compartmental storage, and secretion. Rat tumor versus islet cells.

A series of 3H-leucine pulse-labeling experiments was carried out with dispersed cells freshly isolated from transplanted rat insulinomas. After secreted fractions were separated, insulin was purified and specific activities were determined for both secreted and average cellular insulins. Labeling patterns in this line of tumor cells were compared with those previously established for isolated rat islets. With both tumors and islets, conversion of labeled proinsulin to insulin occurred to the same extent by 2.5 h, suggesting similar onset and half-time of proteolysis in these cells. However, total cellular insulin in tumors attained a threefold higher specific activity than in islets. Because total B-cell mass in these tumors was unknown, either a more rapid proinsulin biosynthesis or diminished cellular storage (or both) could lead to this faster fractional replacement of total stored insulin. Insulin secretion in these tumor cells was insensitive to high glucose but responded, albeit poorly, to leucine plus 3-isobutyl-1-methylxanthine (IBMX). Under all secretory conditions tested, tumor cells continuously secreted insulin at elevated fractional rates, which were slightly higher than fractional insulin secretory rates in maximally glucose-stimulated islets. In contrast with normal islets, newly synthesized insulin was stored homogeneously in tumor cells, and compartmental storage characteristics were not generated by incubation with either 20 mM glucose or leucine plus IBMX in the marking period. Thus, preferential secretion of insulin was never observed in tumor cells.(ABSTRACT TRUNCATED AT 250 WORDS)

1-Methyl-3-isobutylxanthine↗
PubMed1982

Evidence that glucose "marks" beta cells resulting in preferential release of newly synthesized insulin.

Studies of isolated islets labeled with radioactive leucine show that glucose at a critical time "marks" islets in such a way as to cause preferential release of newly synthesized insulin. The preferential release of insulin from marked islets is relatively independent of subsequent secretagogues or rates of insulin secretion. Previous kinetic studies have indicated that the critical time at which marking occurs is after proinsulin biosynthesis but before the secretory event. Thus, secretory cells may regulate the diversion of newly synthesized material for immediate release as it is approaching or transiting the Golgi apparatus.

1-Methyl-3-isobutylxanthine↗
PubMed1982

Heterogeneity and compartmental properties of insulin storage and secretion in rat islets.

To investigate compartmental properties of insulin storage and secretion, isolated rat islets were used for pulse-labeling experiments, after which proinsulin and insulin were purified rigorously. Processing of proinsulin to insulin neared completion by 3 h without additional loss of either radioactive peptide by cellular or extracellular proteolysis. The amount of labeled hormone rapidly diminished in islets; it was secreted at a higher fractional rate than immunoreactive insulin, resulting in secreted insulin's having a higher specific activity than the average cellular insulin. Newly synthesized insulin, therefore, was secreted preferentially. Changes in the specific activity of secreted and cellular insulin with time were consistent with changes predicted for islets containing 33% of their total insulin in a glucose-labile compartment. Predictions were based on steady-state analysis of a simple storage-limited representation of B cell function. Islets from either the dorsal or ventral part of the pancreas also contained 33% of their total insulin in a glucose-labile compartment. The same compartment was mobilized by 20 mM glucose, 50 mM potassium + 2 mM glucose, or 20 MM glucose + 1 mM 3-isobutylmethylxanthine as indicated by the specific activity ratio of secreted vs. cellular insulin, even though average secretion rates with these stimuli differed by more than threefold. In the absence of calcium, the effectiveness of 20 mM glucose as a secretagogue declined markedly, and the older stored insulin was preferentially mobilized because secreted insulin had a lower rather than a higher specific activity than cellular insulin. Results provide insight into the mechanisms of nonrandom mobilization and secretion of insulin form the B cell.

Animals↗
PubMed1981

Effect of variations in islet size and shape on glucose-stimulated insulin secretion.

The present study considers the effects of differences islet size and shape on in vitro glucose-stimulated insulin secretion. Islets were obtained from young rats and rapidly sorted into different size categories before incubation with 16.7 mM glucose. Subsequently, the diameters of each islet were measured and estimates of surface area and volume, assuming various spheroidal or ellipsoidal shapes, were obtained for each islet. These various figures were correlated with the amount of insulin secreted from the same islets and a regression curve was generated for each different islet shape. The results indicate that insulin secretion rates increased directly as a function of islet size (volume or surface area), regardless of islet shape (r = 0.78, p less than .01); thus, islet size is of major importance in predicting insulin secretion and studies utilizing isolated islets should be normalized for this factor. Measurements of islet diameter provide an easy solution to this problem.

Animals↗
PubMed1981

Diabetes induced with multiple subdiabetogenic doses of streptozotocin: lack of protection by exogenous superoxide dismutase.

The addition of exogenous superoxide dismutase (SOD) was examined as a possible means of protecting B-cells of mice against either the immediate or delayed toxicity caused by multiple injections of low doses of streptozotocin (Sz). Three different routes of SOD administration (i.p. and i.v. injection and continuous s.c. infusion) and several different doses and schedules were tried. In addition, a long-acting derivative of SOD was synthesized and tested. Despite the observation of a modest delay in the onset of diabetes in one experiment, no protective effect of SOD on the progressive elevation of blood glucose concentrations was evident in the majority of studies. Moreover, a loss in pancreatic insulin content and a tripling of pancreatic glucagon content occurred in all mice treated with low dosages of Sz, irrespective of whether or not either SOD or a long-acting derivative of SOD was administered. Finally, in parallel experiments in vitro, this enzyme was ineffective in protecting isolated rat islets from the acute toxicity of exposure to Sz on glucose-stimulated insulin release.

Animals↗
PubMed1980

New instrumentation for determining flexure breaking strength of capsule-shaped tablets.

New instrumentation to measure the flexure breaking strength of capsule-shaped tablets was developed. It consisted of a mechanical linkage to apply the breaking load at a uniform rate and a strain-gauge instrumented cantilever beam to convert the load to a proportional millivolt response on a recorder. A recorder tracing was obtained of increasing load with time, with a break in the tracing denoting the tablet's flexure breaking strength. Measurements were made for different tablet hardnesses, and a plot of tablet hardness versus flexure breaking strength yielded a profile of the mechanical strength of the tablet. The instrumentation was shown to have application for determining the effects of tablet thicknesses, tablet ingredients, tablet sizes, cup depths, and bisect dimensions on tablet strength.

Capsules↗
PubMed1980

Effect of age on leucine-induced insulin secretion by the beta-cell.

We have previously shown that aging is associated with a marked decrease in glucose-stimulated insulin release by the beta-cell. To determine whether this age-related defect occurs with other insulin secretagogues, we have investigated leucine-stimulated insulin release. Islets of Langerhans were isolated from 2- and 12-month-old rats, and incubated with 5-20 mM 5-20 mM leucine or with 16.7 mM glucose. Islets from 12-month-old rats showed a decline in rate of leucine-induced secretion as compared to islets of 2-month-old donors (i.e., mean (+/- SEM) insulin secretion at 20 mM leucine was 0.79 (+/- 0.06) and 1.17 (+/- 0.09) microU/min/islet), respectively for 12- and 2-month-old rats. beta-cell number is increased in islets from 12-month-old donors, and when this increase is taken into account, the average beta-cell from 12-month-old donors secretes only one-half the rate of beta-cells from 2-month-old donors. These findings are comparable to those seen after glucose-stimulation, and emphasize the potential global nature of the age-related defect in beta-cell function.

Aging↗
PubMed1979

Effect of age on glucose-stimulated insulin release by the beta-cell of the rat.

To assess the effect of age on beta-cell insulin release, collagenase-isolated islets of Langerhans were obtained from rats aged 2--18 mo and incubated with increasing concentrations of glucose. Similar islets were analyzed for insulin content or subjected to morphometric measurements to identify both the number of beta-cells and the volume of beta-granules per islet. In parallel studies, the islet content of intact pancreata was also determined. The results showed that beta-cell number increased from 2,300 t0 5,000 cells as rats aged from 2 to 18 mo and islet insulin content doubled. However, glucose-stimulated insulin release decreased progressively with age, and this was especially striking when considered in terms of the increase in number of beta-cells/islet; e.g., mean (+/- SEM) insulin secretion (nanounits per minute per beta-cell) of islets incubated with 450 mg/dl of glucose was 1.3 (+/- 0.02), 1.0 (+/- 0.1), 0.4 (+/- 0.05), and 0.3 (+/- 0.01), respectively for 2-, 6-, 12-, and 18-mo-old rats. Thus, insulin secretion per beta-cell was decreased, despite increased stores of insulin per cell. These findings demonstrate that the aging process leads to a profound defect in glucose-stimulated insulin release from the beta-cell. Whether this is a global secretory defect, or solely a failure of the beta-cell to respond to glucose, remains to be defined.

Aging↗
PubMed1978

Stability of CAB contact lenses with hydration.

The effects of hydration on the base curve of CAB lenses were measured with a radiuscope. A significant amount of lens warpage and variability in curvature was detected in all lenses under conditions of continuous hydration. Thinner lenses flattened more than thicker lenses of the same power. Lenses of greater minus power flattened more than lenses of less minus power for a given lens thickenss. Plus power lenses were more stable than minus power lenses. Control lenses, stored dry, did not flatten or warp.

Absorption↗
PubMed1976

A possible role for insulin in the altered capability for hepatic enzyme adaptation during aging.

The pattern of change in the concentration of immunoreactive insulin in portal vein blood during a 7-hour period following intragastric administration of glucose to fasted, male Sprague-Dawley rats is modified both in magnitude and time course of response as rat age increases from 2- to 24-months. This alteration in the control of insulin levels probably is not the consequence of modifications in the availability of administered glucose to the pancreas. A similar modification in the control of insulin secretion also is evident when pancreatic islets isolated from fasted rat donors aged 2- to 24-months are perifused with glucose in vitro. This may represent the first demonstration of an altered response of aging animals which is expressed in the same way in an isolated in vitro system.

Adaptation, Physiological↗
PubMed1976

Relationship between microsomal membrane permeability and the inhibition of hepatic glucose-6-phosphatase by pyridoxal phosphate.

Arion et al; (Arion, W. J., Wallin, B. K., Lange A. J., and Ballas, L. M. (1975) Mol. Cell. Biochem. 6, 75-83) propsed a model for glucose-6-phosphatase in which the substrate was transported across the microsomal membrane by a carrier before hydrolysis on the cisternal side. Evidence to support this model has been obtained by studying the inhibition of the enzyme by pyridoxal-P. Pyridoxal-P was a linear noncompetitive inhibitor of glucose-6-phosphatase (EC 3.1.3.9) in freshly isolated ("intact") microsomes from rat liver. Pyridoxol-P was a much less effective inhibitor and no inhibition was observed with pyridoxamine-P. When microsomes were subjected to nitrogen cavitation, treatment with solium deoxycholate, or glutaraldehyde fixation, the Km of glucose-6-phosphatase for glucose-6 P decreased from approximately 6 mM to approximately 2.5 mM; the corresponding change in the Vmax ranged from-10% to +40%. The same procedures decreased the inhibition of glucose-6-phosphatase by pyridoxal-P several-fold. No inhibition by pyridoxal-P was observed in a preparation of glucose-6-phosphatase purified approximately 20 fold (on the basis of Vmax) from micoromes. A nondialyzable inhibitor was apparently formed when intact microsomes were reacted with pyridoxal-P and NaBH4; this inhibition was also reversed by procedures which changed the kinetic properties of glucose-6-phosphatase.

Animals↗
PubMed1972

Neuropathology.

Explore the source record for details and available documents.

Animals↗