Intra-operative bradycardia in a patient with Alzheimer's disease treated with two cholinesterase inhibitors.
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Aged↗
Biomedical subjects
P M Jones
Publications and source records attributed to P M Jones.
A role for kisspeptin in islet function.
AIMS/HYPOTHESIS: We investigated the production of kisspeptin (KISS1) and the KISS1 receptor, GPR54, in pancreatic islets and determined the effects of exogenous kisspeptin on insulin secretion. METHODS: RT-PCR and immunohistochemistry were used to detect expression of KISS1 and GPR54 mRNAs and the production of KISS1 and GPR54 in human and mouse islets and in beta (MIN6) and alpha- (alphaTC1) cell lines. The effects of KISS1 on basal and glucose-induced insulin secretion from mouse and human islets were measured in a perifusion system. RESULTS: KISS1 and GPR54 mRNAs were both detected in human and mouse islets, and GPR54 mRNA expression was also found in the MIN6 and alphaTC1 endocrine cell lines. In sections of mouse pancreas, KISS1 and GPR54 immunoreactivities were co-localised in both beta and alpha cells within islets, but were not detected in the exocrine pancreas. Exposure of mouse and human islets to KISS1 caused a stimulation of glucose-induced (20 mmol/l) insulin secretion, but had no effect on the basal rate of secretion at a sub-stimulatory concentration of glucose (2 mmol/l). In contrast, KISS1 inhibited insulin secretion from MIN6 cells at both 2 and 20 mmol/l glucose. KISS1 had no significant effect on glucagon secretion from mouse islets. CONCLUSIONS/INTERPRETATION: This is the first report to show that the GPR54/KISS1 system is expressed in the endocrine pancreas, where it influences beta cell secretory function. These observations suggest an important role for this system in the normal regulation of islet function.
Animals↗
Direct regulation of insulin secretion by angiotensin II in human islets of Langerhans.
AIMS/HYPOTHESIS: This study aimed to identify the expression of angiotensin II receptors in isolated human islets and beta cells and to examine the functional consequences of their activation. MATERIALS AND METHODS: Single-cell RT-PCR was used to identify whether human islet cells express mRNA for type 1 angiotensin II receptors (AT(1)), and western blotting was used to determine AT(1) protein expression by human islets and MIN6 beta cells. We measured changes in intracellular calcium by microfluorimetry using Fura 2-loaded MIN6 cells and human islet cells. Dynamic insulin secretory responses were determined by RIA following perifusion of human islets and MIN6 cells. RESULTS: Human islets expressed mRNAs for both the angiotensin precursor, angiotensinogen, and for angiotensin-converting enzyme. In addition, human and mouse beta cells expressed AT(1). These were functionally coupled to increases in intracellular calcium, which occurred at least in part through phospholipase-C-sensitive mechanisms and calcium influx through voltage-operated calcium channels. Short-term exposure of human islets and MIN6 cells to angiotensin II caused a rapid, short-lived initiation of insulin secretion at 2 mmol/l glucose and potentiation of insulin secretion induced by glucose (at 8 and 16.7 mmol/l). CONCLUSIONS/INTERPRETATION: These data demonstrate that the AT(1) is expressed by beta cells and that angiotensin II effects a short-lived and direct stimulation of human and mouse beta cells to promote insulin secretion, most probably through elevations in intracellular calcium. Locally produced angiotensin II may be important in regulating a coordinated insulin secretory response from beta cells.
Angiotensin Amide↗
Multidrug resistance in parasites: ABC transporters, P-glycoproteins and molecular modelling.
Parasitic diseases, caused by protozoa, helminths and arthropods, rank among the most important problems in human and veterinary medicine, and in agriculture, leading to debilitating sicknesses and loss of life. In the absence of vaccines and with the general failure of vector eradication programs, drugs are the main line of defence, but the newest drugs are being tracked by the emergence of resistance in parasites, sharing ominous parallels with multidrug resistance in bacterial pathogens. Any of a number of mechanisms will elicit a drug resistance phenotype in parasites, including: active efflux, reduced uptake, target modification, drug modification, drug sequestration, by-pass shunting, or substrate competition. The role of ABC transporters in parasitic multidrug resistance mechanisms is being subjected to more scrutiny, due in part to the established roles of certain ABC transporters in human diseases, and also to an increasing portfolio of ABC transporters from parasite genome sequencing projects. For example, over 100 ABC transporters have been identified in the Escherichia coli genome, but to date only about 65 in all parasitic genomes. Long established laboratory investigations are now being assisted by molecular biology, bioinformatics, and computational modelling, and it is in these areas that the role of ABC transporters in parasitic multidrug resistance mechanisms may be defined and put in perspective with that of other proteins. We discuss ABC transporters in parasites, and conclude with an example of molecular modelling that identifies a new interaction between the structural domains of a parasite P-glycoprotein.
ATP Binding Cassette Transporter, Subfamily B, Mem↗
Photoelectron spectroscopic and electronic structure studies of CH(2)O bonding and reactivity on ZnO surfaces: steps in the methanol synthesis reaction.
Adsorption of CH(2)O on ZnO(0001) has been investigated using XPS, NEXAFS, variable-energy photoelectron spectroscopy (PES), and density functional theory (DFT) calculations. CH(2)O is chemisorbed on the (0001) surface at 130 K. Its C1s XPS peak position at 292.7 eV and NEXAFS sigma shape resonance at 302.6 eV are consistent with an eta(1) bound surface geometry. Geometry optimized DFT calculations also indicate that CH(2)O is bound to the Zn(II) site in an eta(1) configuration through its oxygen atom. The variable-energy PES of the eta(1) bound CH(2)O/ZnO(0001) complex exhibits four valence band features at 21.2, 16.4, 13.8, and 10.7 eV below the vacuum level providing an experimental and theoretical description of this surface interaction. Annealing the ZnO(0001)/CH(2)O surface complex to 220 K decomposes the chemisorbed CH(2)O, producing formyl (291.5 eV), methoxide (290.2 eV), and formate (293.6 eV) intermediates. Thus this reaction coordinate involves the conversion of an oxygen bound formaldehyde to a carbon bound formyl species on ZnO(0001). Only formate is formed on the ZnO(100) surface. DFT is used to explore surface intermediates and the transition state in the methanol synthesis reaction (MSR). The bonding interactions of H(2), CO, CH(3)O(-), HCO(-), and trans-HCOH to the ZnO(0001) surface are elucidated using geometry optimization. H(2) was found to be heterolytically cleaved on the ZnO(0001) surface, and carbon monoxide, formyl, and methoxide are calculated to be eta(1) bound. These results are consistent with observed metal oxide surface reactivity where heterolytic bond cleavage is dominant. The oxygen atom in the bound formyl was found to be activated for attack by a proton. This results in the planar eta(1) bound trans-HCOH surface species. The transition state in the gas phase rearrangement of trans-HCOH to formaldehyde was calculated to have a barrier of 31 kcal/mol. The correlation diagram for this rearrangement in the gas phase indicates that configuration interaction at the crossing of two levels helps to lower the barrier. A transition state calculation was also performed for this rearrangement on the ZnO(0001) surface. The surface transition state geometry is significantly different than the gas phase. The surface geometry is no longer planar (23 degrees dihedral angle) and is displaced parallel to the surface. Interaction with the Zn(II) site at the crossing of surface bound CH(2)O and trans-HCOH levels further lowers the barrier to rearrangement relative to gas phase by 9 kcal/mol. The rearrangement of trans-HCOH (carbon bound) to CH(2)O (oxygen bound) on ZnO(0001) was calculated to be the overall barrier of the MSR reaction.
Journal Article↗
The ABC transporter structure and mechanism: perspectives on recent research.
ATP-binding cassette (ABC) transporters are multidomain integral membrane proteins that utilise the energy of ATP hydrolysis to translocate solutes across cellular membranes in all phyla. ABC transporters form one of the largest of all protein families and are central to many important biomedical phenomena, including resistance of cancers and pathogenic microbes to drugs. Elucidation of the structure and mechanism of ABC transporters is essential to the rational design of agents to control their function. While a wealth of high-resolution structures of ABC proteins have been produced in recent years, many fundamental questions regarding the protein's mechanism remain unanswered. In this review, we examine the recent structural data concerning ABC transporters and related proteins in the light of other experimental and theoretical data, and discuss these data in relation to current ideas concerning the transporters' molecular mechanism.
ATP-Binding Cassette Transporters↗
ACTH stimulates insulin secretion from MIN6 cells and primary mouse and human islets of Langerhans.
It has previously been suggested that ACTH and ACTH-related peptides may act as paracrine modulators of insulin secretion in the islets of Langerhans. We have, therefore, examined the expression and function of the ACTH receptor (the melanocortin 2 receptor, MC2-R) in human and mouse primary islet tIssue and in the MIN6 mouse insulinoma cell line. Mouse MC2-R mRNA was detected in both MIN6 cells and mouse islet tIssue by PCR amplification of cDNA. In perifusion experiments with MIN6 pseudo-islets, a small, transient increase in insulin secretion was obtained when ACTH(1-24) (1 nM) was added to medium containing 2 mM glucose (control) but not when the medium glucose content was increased to 8 mM. Further investigations were performed using static incubations of MIN6 cell monolayers; ACTH(1-24) (1 pM-10 nM) provoked a concentration-dependent increase in insulin secretion from MIN6 monolayer cells that achieved statistical significance at concentrations of 1 and 10 nM (150 +/- 13.6% basal secretion; 187 +/- 14.9% basal secretion, P<0.01). Similar responses were obtained with ACTH(1-39). The phosphodiesterase inhibitor IBMX (100 microM) potentiated the responses to sub-maximal doses of ACTH(1-24). Two inhibitors of the protein kinase A (PKA) signaling pathway, Rp-cAMPS (500 microM) and H-89 (10 microM), abolished the insulin secretory response to ACTH(1-24) (0.5-10 nM). Treatment with 1 nM ACTH(1-24) caused a small, statistically significant increase in intracellular cAMP levels. Secretory responses of MIN6 cells to ACTH(1-24) were also influenced by changes in extracellular Ca2+ levels. Incubation in Ca2+-free buffer supplemented with 0.1 mM EGTA blocked the MIN6 cells' secretory response to 1 and 10 nM ACTH(1-24). Similar results were obtained when a Ca2+ channel blocker (nitrendipine, 10 microM) was added to the Ca2+-containing buffer. ACTH(1-24) also evoked an insulin secretory response from primary tIssues. The addition of ACTH(1-24) (0.5 nM) to perifusions of mouse islets induced a transient increase in insulin secretion at 8 mM glucose. Perifused human primary islets also showed a secretory response to ACTH(1-24) at basal glucose concentration (2 mM) with a rapid initial spike in insulin secretion followed by a decline to basal levels. Overall the results demonstrate that the MC2-R is expressed in beta-cells and suggest that activation of the receptor by ACTH initiates insulin secretion through the activation of PKA in association with Ca2+ influx into beta-cells.
1-Methyl-3-isobutylxanthine↗
Neonatal accessory digits: a survey of practice amongst paediatricians and hand surgeons in the United Kingdom.
AIM: To describe the management of neonatal accessory digits, comparing views of paediatricians with those of hand surgeons, giving particular emphasis to the form of partial, ulnar duplication of the little finger (ulnar or postaxial polydactyly type B) which has a narrow pedicle. METHODS: Postal questionnaire of management preference using three photographs of ulnar accessory digits of varying complexity. RESULTS: The response rate was 64% in 234 paediatricians and 25% in 260 surgeons. All respondents would intervene in cases of ulnar polydactyly type B with a narrow pedicle: 79% of paediatricians but only 67% of hand surgeons would recommend referral of these cases for specialist assessment, the remainder advocating ligation by the paediatrician in the nursery. Paediatricians and neonatologists working in regional centres or with an on-site specialist service were more likely to refer. There was almost unanimous agreement on the management of the most complex case, but no general consensus on that of the simplest form. CONCLUSION: There is uncertainty and inequality in initial treatment decisions for infants with all but the most complex of accessory digits. Despite published evidence that ligation gives satisfactory results, most respondents in this survey advocate specialist referral, with evidence that the availability of specialist services influences decision making.
Humans↗
Calcium-dependent translocation of cytosolic phospholipase A2 in pancreatic beta-cells.
Cytosolic phospholipase A(2)(cPLA(2)), an enzyme responsible for the generation of arachidonic acid, is located in the cytosolic compartment in most tissues and it translocates to membrane compartments when activated. We found that cPLA(2) distribution in pancreatic beta-cells is different from that of most other mammalian cells: it is evenly distributed throughout the beta-cell, in both cytoplasmic and nuclear compartments. Agents that increased intracellular Ca(2+) in the MIN6 beta-cell line also stimulated a redistribution of cPLA(2) immunoreactivity such that the majority of the enzyme moved from the nucleus to the cytoplasm. The time course of events was compatible with the elevation in Ca(2+) being responsible for translocation of cPLA(2). These observations suggest that cPLA(2) may be compartmentalised in unstimulated beta-cells, perhaps to limit its access to substrate prior to elevations in intracellular Ca(2+).
Calcium↗
Conversion electron cascades in 254(102)No.
The spectrum of prompt conversion electrons emitted by excited 254No nuclei has been measured, revealing discrete lines arising from transitions within the ground state band. A striking feature is a broad distribution that peaks near 100 keV and comprises high multiplicity electron cascades, probably originating from M1 transitions within rotational bands built on high K states.
Journal Article↗
Role of adenine nucleotides in insulin secretion from MIN6 pseudoislets.
Insulin secretion from MIN6 cells configured as cell aggregates by culture on a gelatin substrate (pseudoislets) is enhanced compared to that of MIN6 cells grown as monolayers on tissue culture plastic, indicating the importance of beta-cell-to-beta-cell proximity for insulin release. In this study we have shown that glucose induced a biphasic release of insulin from pseudoislets, whereas the amplitude and duration of the responses of equivalent monolayer cells were much reduced. Purinergic aqonists have been implicated in intercellular communication between beta-cells, so we investigated whether adenine nucleotides co-released with insulin are responsible for the enhanced secretory responses of pseudoislets. We have demonstrated that MIN6 cells express purinergic A(1) and P2Y receptors, and that adenine nucleotides increased [Ca(2+)](i) with an efficacy of agonists being ATP > ADP > AMP. However, neither suramin nor the more selective A(1) antagonist 1,3-dipropyl-8-cyclopentylxanthine reduced glucose-induced insulin secretion from pseudoislets, and stimulation of monolayer cells with a range of adenine nucleotides did not enhance glucose-induced secretion. These results suggest that enhanced secretion from MIN6 pseudoislets is not due to increased paracrine/autocrine action of adenine nucleotides.
Adenine Nucleotides↗
Co-ordinated Ca(2+)-signalling within pancreatic islets: does beta-cell entrainment require a secreted messenger.
Isolated beta-cells are heterogeneous in sensory, biosynthetic and secretory capabilities, however, to enable efficient and appropriate secretion, cellular activity within the intact islet is synchronised. Historically, the entrainment of activity to a common pattern has been attributed to gap-junction mediated cell-to-cell communication. Although clearly influential, the possibility remains for other local synchronising mechanisms. In this study, we have used small clusters of insulin-secreting MIN6 cells to assess how contact-dependent, homotypic interactions between cells influences nutrient- and non-nutrient- evoked Ca(2+)-handling and insulin secretion, and to determine whether a secreted product plays a role in the synchronisation of oscillatory activity. Tolbutamide evoked a concentration-dependent recruitment of active cells within cell clusters, both in terms of numbers of cells and amplitude of the evoked Ca(2+)-response. The change in [Ca(2+)](i) was characteristically oscillatory above a mean elevated plateau, and was in phase between member cells of an individual cluster. Even at maximal concentrations (100 microM) some cells within a cluster responded before their immediate neighbours. Subsequent oscillatory behaviour then became entrained between member cells within that cluster. Inhibiting exocytosis using the microtubule inhibitors vincristine and nocodazole, or the adrenergic agent noradrenaline, did not prevent tolbutamide-evoked oscillatory changes in [Ca(2+)](i) but did reduce the probability of obtaining synchronous activity within an individual cluster. Above a threshold glucose concentration, the number of cells secreting insulin increased, without a commensurate change in secretory efficiency. This recruitment of cells secreting insulin mirrored Ca(2+) data that showed a glucose-dependent increase in cell number, without a change in the mean basal-to-peak change in [Ca(2+)](i). Together these data suggest that synchronised behaviour in MIN6 cells is dependent, in part, on a secreted factor that acts in a local paracrine fashion to recruit heterogeneous individual cellular activity into an organised group response.
Animals↗
Interdependence of steroidogenesis and shape changes in Y1 adrenocortical cells: studies with inhibitors of phosphoprotein phosphatases.
Y1 adrenocortical cells respond to activators of the cyclic AMP-dependent protein kinase (PKA) signalling pathway not only with increases in steroid secretion but also with a characteristic change in cell morphology from flat and adherent to round and loosely attached. This change of shape, which may facilitate cholesterol transport to the mitochondrion, requires tyrosine dephosphorylation of the focal adhesion protein, paxillin, and can be blocked by inhibitors of phosphotyrosine phosphatase (PTP) activity. In a previous study we demonstrated that inhibition of phosphoserine/threonine phosphatase 1 and 2A (PP1/2A) activities caused a similar morphological response to PKA activation whilst opposing the effects on steroid production. We have now investigated the responses to PKA activation and inhibition of PP1/2A and used PTP inhibitors to examine the relationship between the morphological changes and enhanced steroid production. Both forskolin (FSK) and the PP1/2A inhibitor, calyculin A (CA), caused rapid and extensive rounding of Y1 cells. FSK-induced cell rounding was reversible and accompanied by a reduction in the tyrosine phosphorylation of paxillin. Rounding was prevented by the PTP inhibitors pervanadate (PV) and calpeptin (CP) and was associated with the maintained tyrosine phosphorylation of paxillin. In contrast, CA-induced cell rounding was not reversible over a 2-h period and was not affected by the presence of PTP inhibitors, and CA had no effect on the tyrosine phosphorylation of paxillin. Although neither CA nor FSK produced any gross changes in cell viability as judged by Trypan Blue exclusion or mitochondrial activity, CA-treated cells showed a marked reduction in total protein synthesis assessed by (35)S-incorporation. The effects of FSK and the PTP inhibitors on cell rounding were reflected in their effects on steroid production since PV and CP also inhibited FSK-stimulated steroid production. These results suggest that the mechanism through which inhibition of PP1/2A activities induces morphological changes in Y1 cells is fundamentally different from that seen in response to activation of PKA. They are consistent with PKA-induced shape changes in adrenocortical cells being mediated through increased PTP activity and the dephosphorylation of paxillin, and support the view that the morphological and functional responses to PKA activation in steroidogenic cells are intimately linked.
Adrenal Cortex↗
ERKs regulate cyclic AMP-induced steroid synthesis through transcription of the steroidogenic acute regulatory (StAR) gene.
Cyclic AMP-dependent expression of the steroidogenic acute regulatory (StAR) protein is thought to be the controlling step for steroid production, but the mechanisms through which external signals are translated into increased transcription of the StAR gene are unknown. We demonstrate that cyclic AMP-induced steroid synthesis is dependent upon the phosphorylation and activation of ERKs and that ERK activation results in enhanced phosphorylation of SF-1 and increased steroid production through increased transcription of the StAR gene. Adenylate cyclase activation with forskolin (FSK) caused a time-dependent increase in ERK activity and translocation from cytoplasm to nucleus, which correlated with an increase in StAR mRNA levels, StAR protein accumulation, and steroidogenesis. Similarly, ERK inhibition led to a reduction in the levels of FSK-stimulated StAR mRNA, StAR protein, and steroid secretion. These effects were attributed to the finding that ERK activity is required for SF-1 phosphorylation, a transcription factor required for the regulation of StAR gene transcription. This conclusion was supported by our demonstration of an ERK-dependent increase in the binding of SF-1 from FSK-treated Y1 nuclei to three consensus double-stranded DNA sequences from the StAR promoter region. These observations suggest that the activation of ERK2/1 by increasing cAMP is an obligatory and regulated stage in the stimulation of steroid synthesis by cyclic AMP-generating stimuli.
Animals↗
Subcutaneous emphysema associated with chest tube drainage.
BACKGROUND: Subcutaneous emphysema may complicate a pneumothorax, but may also occur as a consequence of its treatment by chest tube drainage. The aim of this study was to evaluate the factors involved in the association between subcutaneous emphysema and chest tube drainage, and the clinical outcomes in these cases. METHODOLOGY: One hundred and sixty-seven patients undergoing chest tube drainage within a 12-month period were evaluated retrospectively. There were 30 reported cases of subcutaneous emphysema (SE). Comparisons were made between those with subcutaneous emphysema and those who did not develop this complication. RESULTS: A total of 134 patient notes were evaluated (25 SE and 109 non-SE). Subcutaneous emphysema was more commonly associated with trauma, bronchopleural fistulae, large and bilateral pneumothoraces, and mechanical ventilation. Subcutaneous emphysema was also associated with prolonged drainage, poor tube placement, tube blockage, side-port migration, and a greater number of chest tubes. Importantly, those with SE had a longer length of stay and increased mortality. CONCLUSION: Subcutaneous emphysema can be spontaneous or traumatic, but is associated with avoidable causes such as inadequate chest tube drainage, particularly due to poor tube placement, anchorage and blockage, and also with side-port migration into the subcutaneous tissue. It is associated with an increased morbidity and mortality, and may indicate the need for urgent chest tube replacement.
Adolescent↗
Accumulation of free 3-hydroxy fatty acids in the culture media of fibroblasts from patients deficient in long-chain l-3-hydroxyacyl-CoA dehydrogenase: a useful diagnostic aid.
BACKGROUND: The diagnosis of long-chain L-3-hydroxy-acyl-coenzyme A dehydrogenase (LCHAD) deficiency frequently requires the study of cultured fibroblasts. We developed such a test that does not require disruption and loss of the cells. METHODS: We measured free 3-hydroxy fatty acids (3-OHFAs) in media of skin fibroblasts cultures from 11 patients with a genetic deficiency of LCHAD and the associated disorder of mitochondrial trifunctional protein (MTFP). Fibroblasts were cultured for 24 h with 100 micromol/L nonisotopic palmitate added. 3-OHFAs were measured by selected-ion monitoring, stable-isotope dilution gas chromatography-mass spectrometry with [(13)C]-labeled internal standards. RESULTS: 3-OH-hexadecanoic and 3-OH-tetradecanoic FAs were increased 14- and 11-fold, respectively, in all patients with LCHAD or MTFP deficiency when compared with control fibroblast cell lines after overnight incubation with palmitate. 3-OH-dodecanoic FA demonstrated a modest, fivefold increase in LCHAD-deficient cells. The concentrations of all 3-OHFAs were similar whether or not the medium samples were hydrolyzed to release conjugated species such as acylcarnitines, suggesting that 3-OHFAs accumulate in the media as free FAs. CONCLUSIONS: Measurement of 3-OHFA excretion from LCHAD- or MTFP-deficient cell lines can be used as a diagnostic tool. Free FAs are the predominant form of these abnormal metabolic intermediates in culture media.
3-Hydroxyacyl CoA Dehydrogenases↗
Phosphoprotein phosphatases regulate steroidogenesis by influencing StAR gene transcription.
The rate-limiting step in steroidogenesis is the transport of cholesterol into the mitochondria, and this is controlled by the steroidogenic acute regulatory (StAR) protein. We have previously shown that inhibition of phosphoprotein phosphatase 1 and 2A (PP1/2A) activities with the PP1/2A inhibitor calyculin A selectively reduces StAR protein expression and thus inhibits the synthesis of steroid hormones. The aim of this study was to determine whether this inhibition of StAR protein expression occurs at the level of transcription of StAR mRNA. We have used a competitive reverse transcription-polymerase chain reaction (RT-PCR) technique to determine whether inhibition of PP1/2A activities has any effect on the levels of StAR mRNA. Exposure of Y1 cells to forskolin significantly increased the expression of StAR mRNA and this forskolin-induced increase was reduced after exposure to Cal A at levels similar to those seen in the controls. These results suggest that cyclic AMP-induced increases in StAR mRNA levels are dependent upon phosphoprotein phosphatase activities.
Adrenal Cortex↗
Depolarizing stimuli reduce Ca(2+)/calmodulin-dependent protein kinase II activity in islets of Langerhans.
Elevations in intracellular Ca(2+) ([Ca(2+)](i)) initiate insulin secretion from pancreatic beta-cells, but the secretory responses become rapidly desensitised to maintained elevations in [Ca(2+)](i). We have investigated the mechanisms underlying the Ca(2+) desensitization of insulin secretion using electrically permeabilized rat islets of Langerhans. Measurements of Ca(2+)/calmodulin-dependent protein kinase II (CaMK II) enzyme activity and immunoreactivity in permeabilized islets demonstrated Ca(2+)-induced reductions in enzyme activity which could not be attributed to reductions in CaMK II immunoreactive protein. Measurements in intact islets demonstrated that the Ca(2+)-induced reduction of CaMK II activity was also operative in intact cells, suggesting that this mechanism may have pathophysiological implications for beta-cell function.
Animals↗