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Biomedical subjects

I Valverde

Publications and source records attributed to I Valverde.

At least 127 records · Page 7Linked to original sources
PubMed1981

The stimulus-secretion coupling of glucose-induced insulin release. XLVII. The possible role of calmodulin.

Pancreatic islets contain calmodulin. This protein activates adenylate cyclase in a subcellular fraction of rat islets in a calcium-dependent fashion. The Km for calmodulin was close to 0.1 microM, well below the concentration of endogenous calmodulin. Trifluoperazine and the trifluoromethylphenothiazine derivative of domperidone inhibited glucose-stimulated insulin release without affecting glucose oxidation by the islets. When insulin release was inhibited by 30% or more, this inhibition coincided with a reduction in the 45Ca net uptake by the islets. Both drugs suppressed the increment in adenylate cyclase activity evoked by calmodulin in a particulate fraction derived from the islets. However, the drugs also decreased basal and NaF-stimulated adenylate cyclase activities. Within limits, these data are compatible with the participation of endogenous calmodulin in the normal process of insulin release.

Adenylyl Cyclases↗
PubMed1981

Organic calcium-antagonists and calcium-ionophores.

Verapamil, suloctidil and other organic calcium-antagonists inhibit calcium translocation from an aqueous medium into a hydrophobic domain medicated by 8-[1-(ethyl-1-carboxy-pyrrole-2)]-4-(2-methylene-4-carboxy-5-methylamino-benzoxazole)-spiro(5,5)hendecan-3,9,11-trimethyl-6,7-dioxane (A23187). The magnitude of this inhibition depends on the verapamil/ionophore concentration ratio, the slope of the dose-action relationship (in semilogarithmic coordinates) being comparable with distinct drugs of vastly different biological potency. Like in intact cells, calcium-antagonists, an effect which apparently depends on a direct interaction with the calcium-binding site of the ionophoretic molecule. Verapamil also inhibits calcium and sodium translocation mediated by 3-methyl-5-bromo-6(7-ethyl-4-hydroxy-3,5-dimethyl-6-oxo-7-[5-ethyl-3-methyl-5-( 5-ethyl-5-hydroxy-6-methyl-2-tetrahydropyranyl)-2 tetrahydrofuryl] heptyl) salicylic acid (X537A). The relative efficiency of suloctidil and its analogues or metabolites to inhibit calcium translocation correlates with their potency to inhibit smooth muscle contraction. These findings suggest that the interference of organic calcium-antagonists with native ionophoretic processes represents a fundamental event in the expression of their biological action.

Calcimycin↗
PubMed1980

The stimulus-secretion coupling of glucose-induced insulin release. XLII. Effects of extracellular pH on insulin release: their dependency on nutrient concentration.

Changes in extracellular pH affected insulin output from pancreatic islets stimulated with either glucose or alpha-ketoisocaproate. The extracellular pH at which the highest secretory response occurred was not identical in all cases, being shifted to alkaline values as the concentration of the nutrient secretagogue was increased. The output of insulin correlated with the nutrient-induced increment in 45Ca net uptake, but not with the rate of nutrient oxidation. By reference to changes in intracellular pH observed in islets exposed to either acidic media or increasing concentrations of alpha-ketoisocaproate, and taking into account a titration curve for the buffering capacity of islet homogenates, the optimal intracellular pH for insulin release was found to approximate a value of 0.09 pH unit below basal pH. It is postulated that, in the process of nutrient-induced insulin release, modest changes in intracellular pH participate in the multifactorial coupling between metabolic, ionic and secretory events.

Animals↗
PubMed1980

Mode of action of clonidine upon islet function: dissociated effects upon the time course and magnitude of insulin release.

Clonidine (0.08 to 80.0 ng/ml) caused a dose-related inhibition of glucose-stimulated insulin release, but failed to affect glucose oxidation, glucose-stimulated 45Ca net uptake, and adenylate cyclase activity in isolated rat islets. Phentolamine antagonized the effect of clonidine upon insulin release. Despite profound inhibition of insulin secretion, the drug failed to affect the time course for the changes evoked by glucose in either 45Ca fractional outflow rate from perfused islets or insulin release from the isolated perfused pancreas. The latter changes were multiphasic, revealing an initial secretory peak, a period of low secretory activity, and a second secretory elevation before establishing a period characterized by a steadily and slowly increasing insulin output. In the clonidine-treated islets, the secretory rate was not significantly different from the basal value during the period after the initial secretory response. Thus, despite continuous stimulation with glucose, insulin release appears as a discontinuous phenomenon, even when little insulin is secreted during the initial phase of stimulation.

Adenylyl Cyclases↗
PubMed1980

The interplay between metabolic and cationic events in islet cells: coupling factors and feedback mechanisms.

In the mechanism of glucose-stimulated insulin release, the coupling between glucose metabolism and the remodelling of cationic fluxes in the B-cell apparently represents a multifactorial process involving changes in the generation rate of H+, reducing equivalents and ATP. This process is susceptible to feedback regulatory mechanisms through which primary changes in cationic movements affect glucose metabolism. The interplay between metabolic and ionic events may participate in the rhythmogenesis of bioelectrical and secretory phenomena.

Adenosine Triphosphate↗
PubMed1979

Calmodulin activation of adenylate cyclase in pancreatic islets.

Pancreatic islets contain calmodulin. The protein binds to a particulate fraction derived from the islets and stimulates adenylate cyclase activity in this subcellular fraction, both phenomena being activated by ionized calcium. A calcium-dependent stimulation of adenylate cyclase by endogenous calmodulin may contribute to the accumulation of adenosine 3',5'-monophosphate evoked by insulin releasing agents in the islet cells.

Adenylyl Cyclases↗
PubMed1979

The stimulus-secretion coupling of glucose-induced insulin release. XXXV. The links between metabolic and cationic events.

When isolated rat islets were exposed to glucose, the concentrations of NADH and NADPH, and the NADH/NAD+ and NADPH/NADP+ ratios were increased. The dose-response curve resembled that characterising the glucose-induced secondary rise in 45Ca efflux, displaying a sigmoidal pattern with a half-maximal value at glucose 7.5 mmol/l. The glucose-induced increase in NAD(P)H was detectable within 1 min of exposure to the sugar. Except for the fall in ATP concentration and ATP/ADP ratio found at very low glucose concentrations (zero to 1.7 mmol/l) no effect of glucose (2.8-27.8 mmol/l) upon the steady-state concentration of adenine nucleotides was observed. However, a stepwise increase in glucose concentration provoked a dramatic and transient fall in the ATP concentration, followed by a sustained increase in both O2 consumption and oxidation of exogenous + endogenous nutrients. This may be essential to meet the energy requirements in the stimulated B-cell. Although no significant effect of glucose upon intracellular pH was detected by the 5,5-dimethyloxazolidine-2,4-dione method, the net release of H+ was markedly increased by glucose, with a hyperbolic dose-response curve (half-maximal response at glucose 2.9 mmol/l) similar to that characterising the glucose-induced initial fall in 45Ca efflux. It is proposed that the generation of both NAD(P)H and H+ participates in the coupling of glucose metabolism to distal events in the secretory sequence, especially the ionophoretic process of Ca2+ inward and outward transport, and that changes in these parameters occur in concert with an increased turn-over rate of high-energy phosphate intermediates.

Adenine Nucleotides↗
PubMed1979

Ionophore-mediated cation translocation in artificial systems. I. A23187-mediated calcium translocation.

The inophore A23187 stimulates the translocation of calcium from an aqueous Hepes buffer into an organic immiscible phase. At saturating calcium concentrations, 2 molecules of ionophore seem to complex each atom of calcium. Consistent with such a stoichiometric behaviour, the apparent ratio of calcium-ionophore association to dissociation rate constants increases as the concentration of ionophore is raised. As a result, at low calcium concentrations, the amount of translocated calcium increases as a power function of A23187 concentration. When allowance is made for such a phenomenon, the relation between calcium translocation and concentration is characterized by usual substrate-receptor binding kinetics.

Anti-Bacterial Agents↗
PubMed1979

Chromatographic pattern of gut glucagon-like immunoreactivity (GLI) in plasma before and during glucose absorption.

In this work we have studied the chromatographic pattern on Bio-Gel P-30 columns of the glucagon-like immunoreactivity (GLI) present in unextracted plasma from normal dogs in the basal state and after intraduodenal administration of glucose. Basal plasma GLI, measured by R-8 antiserum, was distributed in four distinct fractions, whose approximate molecular weights were: greater than 30000 delta (Fraction I), 10000 delta (Fraction II), 3500 delta (Fraction III) and 2000 delta (Fraction IV). Fraction I accounted for the highest percent of total immunoreactivity. The increase in plasma GLI during glucose absorption was due to a significant increase of Fraction II, which may well correspond to tissue GLI Peak I, while no significant changes were evident in the other three fractions. The fact that tissue Peak I (or plasma Fraction II) ssems to be the factor secreted during glucose absorption puts the material/s of this molecular size in the first place for further investigation.

Animals↗
PubMed1978

[Circulating types of human glucagon (author's transl)].

In the plasma of healthy subjects, 4 fractions of immunoreactive glucagon are found. The first has a molecular weight of about 160000, the second of 9000, the third 3500 and the fourth about 2000. The third probably corresponds to the intact hormone glucagon. In cirrhosis of the liver and diabetes mellitus, a statistically significant rise in the third fraction has been found. In patients with tumors of the pancreatic A-cells, in addition to the third fraction the second in particular was also increased: it may be a precursor of the glucagon molecule. In chronic renal insufficiency, fractions 2 and 3 were as markedly increased as in glucagonoma, which suggests a role for the kidney in the decomposition of glucagon. The pathophysiologic significance of the four immunoreactive fractions of glucagon cannot yet be assessed with certainty.

Antibody Specificity↗
PubMed1976

Distribution of plasma glucagon immunoreactivity in a patient with suspected glucagonoma.

Gel filtration of plasma from a patient with a clinical syndrome of glucagonoma and a total plasma glucagon level of 2600 pg/ml, revealed the four glucagon immunoreactive fractions found in normal subjects. The total hyperglucagonemia observed was due to high levels of true glucagon and proglucagon moieties. The so-called "big plasma glucagon" (BPG) measured 190 pg/ml (normal average 113 +/- 79 pg/ml, Mean +/- SD, N = 10); the large glucagon immunoreactivity, LGI (9000 mol wt), measured 625 pg/ml (normal average 11 +/- 16 pg/ml); the true glucagon accounted for 1435 pg/ml (normal average 31 +/- 29 pg/ml); and the small glucagon immunoreactive fraction (approximately 2000 mol wt) measured 35 pg/ml (normal average 26 +/- 18 pg/ml). The high levels of LGI, considered a candidate for proglucagon, may reflect the increased secretory activity of the tumor.

Adenoma, Islet Cell↗
PubMed1975

Glucagon: role in the hyperglycemia of diabetes mellitus.

Glucagon suppression by somatostatin reduces or abolishes hyperglycemia in dogs made insulin-deficient by somatostatin, alloxan, or total pancreatectomy. This suggests that the development of severe diabetic hyperglycemia requires the presence of glucagon, whether secreted by pancreatic or newly identified gastrointestinal A cells, as well as a lack of insulin. Glucagon suppression could improve therapeutic glucoregulation in diabetes.

Animals↗
PubMed1975

Heterogeneity of plasma glucagon immunoreactivity in normal, depancreatized, and alloxan-diabetic dogs.

Filtration of basal plasma from normal, alloxan-diabetic, and depancreatized dogs on Bio Gel P-10 yielded four glucagon-immunoreactive fractions. One of them appeared in the true glycagon area with the glucagon-125I (3500 mol vt). Of the other three, one appeared in the void volume (greater than 20000 mol wt), another just before the insulin-125I (congruent to 9000 mol wt), and the last one close to the salt peak (less than 2000 mol wt). The increase of total plasma glucagon immunoreactivity observed in depancreatized and alloxan diabetic dogs was mainly due to an increase in the 3500 and 9000 molecular-weight fractions. Arginine infusion in depancreatized dogs caused an increase in the 3500 molecular-weight fraction. Somatostatin or insulin infusion in depancreatized and alloxan-diabetic dogs resulted in disappearance of the 3500 molecular-weight fraction.

Animals↗