A5023439457- Pancreatic function and diabetes
- Diet, Metabolism, and Disease
- Adipose Tissue and Metabolism
- Metabolism, Diabetes, and Cancer
- Diabetes and associated disorders
- Cannabis and Cannabinoid Research
- Diet and metabolism studies
- Aldose Reductase and Taurine
- Neuroscience and Neuropharmacology Research
- Diabetes Management and Research
- Neuroendocrine Tumor Research Advances
- Receptor Mechanisms and Signaling
- Diabetes Treatment and Management
- RNA Interference and Gene Delivery
- Pancreatitis Pathology and Treatment
- Adenosine and Purinergic Signaling
- Photoreceptor and optogenetics research
- Natural Antidiabetic Agents Studies
- Renal Transplantation Outcomes and Treatments
- Genetics and Neurodevelopmental Disorders
- GABA and Rice Research
- Glycosylation and Glycoproteins Research
- Neuroscience of respiration and sleep
- Advanced Drug Delivery Systems
- Gestational Diabetes Research and Management
Universidad Complutense de Madrid
2010-2025
Boston University
2016
University of Geneva
1994
Universidad Autónoma de Madrid
1990
European Association for the Study of Diabetes
1978
Pfizer (United States)
1978
Umeå University
1977-1978
Nutrient metabolism was examined with regard to insulin secretion in purified rat islet beta- and non-beta-cells, beta-cell lines, hepatocytes. Lactate dehydrogenase (LDH) activity (nanomoles.min-1.mg protein-1) remarkably low the glucose-sensitive INS-1 cell line (15.7) beta-cells (22.3). Thus, LDH respectively 8-, 122-, 17-, 136-fold lower than non-beta, liver, HIT-T15, RINm5F cells. Plasma membrane lactate transport 3-10-fold or cells other types. Conversely, mitochondrial glycerol...
We explored the role of Krebs cycle enzyme fumarate hydratase (FH) in glucose-stimulated insulin secretion (GSIS). Mice lacking Fh1 pancreatic β cells (Fh1βKO mice) appear normal for 6-8 weeks but then develop progressive glucose intolerance and diabetes. Glucose tolerance is rescued by expression mitochondrial or cytosolic FH not deletion Hif1α Nrf2. Progressive hyperglycemia Fh1βKO mice led to dysregulated metabolism cells, a decrease glucose-induced ATP production, electrical activity,...
Analysis of precedent and new data should allow now then to suggest modifications for a future integral view the stimulus-secretion coupling glucose-induced insulin secretion. The main purpose this review is supply only biochemical considerations about some metabolic pathways implicated in process It emphasized that glucose β-cells’ threshold activate secretion (5 mM) might depend on predominance anaerobic glycolysis at basal concentration. This argues against phosphoenolpyruvate (PEP) over...
Integration of old and recent experimental data consequences is needed to correct help improve the hypothetical mechanism responsible for stimulus–secretion coupling glucose-induced insulin secretion. The main purpose this review supply biochemical considerations about some metabolic pathways implicated in process It emphasized that glucose β-cells’ threshold activate secretion (5 mM) might depend on predominance anaerobic glycolysis at basal concentration. This argues against...
In pancreatic β-cells, glutamate dehydrogenase (GDH) modulates insulin secretion, although its function regarding specific secretagogues is unclear. This study investigated the role of GDH using a β-cell–specific knockout mouse model, called βGlud1 −/− . The absence in islets isolated from –/– mice resulted abrogation release evoked by glutamine combined with 2-aminobicyclo[2.2.1]heptane-2-carboxylic acid or l-leucine. Reintroduction fully restored secretory response. Regarding glucose...
The influence of 48 h starvation on glucose-induced changes palmitate metabolism and insulin release in isolated rat islets was investigated. (1) Islet response to 20 mM-glucose abolished after starvation, it restored by 0.25 mM-2-bromostearate, an inhibitor fatty acid oxidation. (2) increase glucose concentration from 3 mM accompanied a 50% decrease the oxidation rate 0.5 mM-[U-14C]palmitate control (fed) islets, concomitant (100%) its incorporation into triacylglycerol phospholipid...
We have demonstrated recently that branched-chain α-keto acid stimulation of insulin secretion is dependent on islet GABA (γ-aminobutyric acid) metabolism: transamination to succinic semialdehyde increased by 2-oxoglutarate, generated in its corresponding α-amino acid. The present work was aimed at investigating whether glucose also promotes metabolism and the latter contributes secretion. Glucose (20 mM) decreased both content release GABA. Gabaculine (1 mM), a transaminase inhibitor,...
The secretory, metabolic, and signaling aspects of glucose/ palmitate interaction on β-cell function have been studied rat islets. Palmitate potentiated the glucose-induced insulin response perifused islets at suprathreshold (>3 mmol/1) sugar concentrations. This potentiating effect could be suppressed by 8-bromocGMP, which also blocks metabolism. did not modify glucose utilization, but it slightly reduced oxidation concomitantly increased lactate production. very low rate (80-fold...
Previous reports have dealt with the hypoglycemic properties of taurine and its effects on insulin secretion by adult fetal isolated islets. We studied presence cellular distribution in rat islets, conditions to evoke release, possible modulatory action secretion. localized techniques double immunolabeling most glucagon-positive cells some somatostatin-positive cells, whereas insulin-positive were not labeled antibody. Although high-glucose stimulation did any a hyposmotic solution (17%...
We have carried out a detailed examination of L-glutamine metabolism in rat islets order to elucidate the paradoxical failure stimulate insulin secretion. L-Glutamine was converted by isolated into GABA (gamma-aminobutyric acid), L-aspartate and L-glutamate. Saturation intracellular concentrations all these amino acids occurred at approx. 10 mmol/l L-glutamine, their half-maximal values were attained progressively increasing (0.3 for GABA; 0.5 1.0 Asp Glu respectively). accumulation...
We have previously shown that oxo-4-methylpentanoate promotes islet GABA (γ-aminobutyric acid) metabolism and stimulates insulin secretion. The main aim of this work was to explore the participation transamination branched-chain 2-oxoacids in these processes with aid several inhibitors enzyme activity. No correlation found between homogenates However, vivo rates correlated better secretion capacity different 2-oxoacids. Gabapentin, a specific inhibitor cytosolic isoenzyme, showed greater...
The existence of functional connexin36 (Cx36) hemichannels in β-cells was investigated pancreatic islets rat and wild-type (Cx36(+/+)), monoallelic (Cx36(+/-)), biallelic (Cx36(-/-)) knockout mice. Hemichannel opening by KCl depolarization studied measuring ATP release changes intracellular (ADP). Cx36(+/+) lost after with 70 mM at 5 glucose; loss prevented 8 20 glucose or 50 μM mefloquine (connexin inhibitor). content higher Cx36(-/-) than not decreased depolarization; Cx36(+/-) showed...
We have previously demonstrated that islet depolarization with 70 mM KCl opens Cx36 hemichannels and allows diffusion of small metabolites cofactors through the β-cell plasma membrane. investigated in this "permeabilized" model whether glycolytic citric acid cycle intermediates stimulate insulin secretion how it correlates ATP production (islet content plus extracellular nucleotide accumulation). Glycolytic (10 mM) stimulated similarly. However, they showed differential sensitivities to...
A detailed study of palmitate metabolism in pancreatic islets subject to different experimental conditions, like varying concentrations glucose, as well fed or starved has allowed us explore the interaction between two main plasma nutrients and its consequences on hormone secretion. Palmitate potentiates glucose-induced insulin secretion a concentration-dependent manner, physiological range both (0–2 mM) glucose (6–20 concentrations; at lower than 6 mM, no metabolic with was apparent....
The specificity of a new somatostatin antiserum (Ab 6) has been investigated using eight different peptide analogues. For this purpose, and all the analogues were tested, in an equimolar concentration range, for their ability to displace 125I-tyr1-somatostatin from its binding antibodies. Analysis displacement curves shows that Ab 6 predominantly recognizes changes at central aminoacid sequence molecule. Its ligand seems be similar other antisera previously described (R-141 A-101).
Our previous work has demonstrated that islet depolarization with KCl opens connexin36 hemichannels in β-cells of mouse pancreatic islets allowing the exchange small metabolites extracellular medium. In this study, opening these been further characterized rat and INS–1 cells. Taking advantage hemicannels’opening, uptake ATP its effect on insulin release were investigated. 70 mM stimulated light emission by luciferin dispersed cells transduced fire-fly luciferase gene: it was suppressed 20...
Noradrenaline inhibits in rat islets the stimulation of insulin secretion induced by glucose and its potentiation palmitate, but signalling system responsible remains unknown. We have tested hypothesis that noradrenaline-induced inhibition is mediated an elevation cyclic GMP (cGMP) levels. The analogue 8-Br-cGMP decreases dose-dependently palmitate glucose-induced secretion, whereas it only slightly affects proper effect glucose. Similarly, abolishes acceleration 45Ca2+ uptake without...
Abstract. In order to know more about the secretory pattern of islet TRH in response glucose and its possible physiological relevance, release this hormone as well that insulin, glucagon, somatostatin was radioimmunologically measured. Whereas secretion immunoreactive insulin by incubated rat islets is known be dose-dependently stimulated glucose, glucagon inhibited glucose. Similarly, palmitate release. Exogenous exerted strong dose-dependent effects on other hormones at same concentration...