scholarly journals The effect of starvation on phosphodiesterase activity and the content of adenosine 3′:5′-cyclic monophosphate in isolated mouse pancreatic islets

1974 ◽  
Vol 142 (3) ◽  
pp. 653-658 ◽  
Author(s):  
Kirsten Capito ◽  
Carl Jørgen Hedeskov
Keyword(s):  
Glucose Metabolism ◽  
Cyclic Amp ◽  
Pancreatic Islets ◽  
Maximum Activity ◽  
Secretory Process ◽  
Phosphodiesterase Activity ◽  
Primary Defect ◽  
Isolated Pancreatic Islets ◽  
Cyclic Monophosphate ◽  
Mouse Pancreatic Islets

1. The concentration of cyclic AMP and the activity of phosphodiesterase were measured in isolated pancreatic islets from fed or 48h-starved mice. 2. Two different phosphodiesterases were detected. Neither the maximum activity nor the Km values of these enzymes were changed by starvation. 3. The concentration of cyclic AMP in non-incubated islets was the same in islets from fed and starved mice. 4. Incubation with 3.3mm-glucose for 5–30min had no effect on the concentration of cyclic AMP, irrespective of the nutritional state of the mice. Incubation with 16.7mm-glucose for 5–30min raised the concentration of cyclic AMP by about 30% in islets from fed mice. This rise was prevented by addition of mannoheptulose (3mg/ml). Incubation with 16.7mm-glucose had no effect on the cyclic AMP content in islets from starved mice. 5. In islets from fed mice 10min incubation with 5mm-caffeine had no effect on the concentration of cyclic AMP in the presence of 3.3 or 16.7mm-glucose, whereas the cyclic AMP content was increased approx. 150% in islets from starved mice. 6. After 10min incubation with 1mm-3-isobutyl-1-methylxanthine in the presence of 3.3 or 16.7mm-glucose the concentration of cyclic AMP was raised by 250% in islets from fed mice and by 400% in islets from starved mice. 7. A threefold function of glucose in the insulin-secretory process is suggested, according to which the decreased islet glucose metabolism is the primary defect in the insulin-secretory mechanism during starvation.

scholarly journals Long-term effects of a high glucose concentration on cyclic nucleotide phosphodiesterase activity in mouse pancreatic islets maintained in tissue culture

1976 ◽  
Vol 156 (2) ◽  
pp. 461-463 ◽  
Author(s):  
C Berne ◽  
A Andersson
Keyword(s):  
Cyclic Amp ◽  
Pancreatic Islets ◽  
Glucose Concentration ◽  
Phosphodiesterase Activity ◽  
Long Term Effects ◽  
Isolated Pancreatic Islets ◽  
Cyclic Amp Phosphodiesterase ◽  
Extracellular Glucose Concentration ◽  
Extracellular Glucose

It has been suggested that the stimulatory effect of glucose on insulin release may be mediated by the adenylate cyclase-cyclic AMP phosphodiesterase system. In this study it was found that exposure of isolated pancreatic islets to an elevated extracellular glucose concentration for 1 week in vitro caused an increase of the cyclic AMP phosphodiesterase activity in the islet cells. These and previous data indicate that there is an increased turnover of cyclic AMP in B-cells exposed for a prolonged time to a high extracellular glucose concentration, which also causes an increased turnover rate of insulin.

Cyclic AMP phosphodiesterase activity in mouse pancreatic islets Effects of calmodulin and phospholipids

1986 ◽  
Vol 111 (4) ◽  
pp. 533-538 ◽  
Author(s):  
Kirsten Capito ◽  
Carl Jørgen Hedeskov ◽  
Peter Thams
Keyword(s):  
Enzyme Activity ◽  
Cyclic Amp ◽  
Adenylate Cyclase ◽  
Pancreatic Islets ◽  
Total Activity ◽  
Particulate Fraction ◽  
Supernatant Fraction ◽  
Phosphodiesterase Activity ◽  
Cyclic Amp Phosphodiesterase ◽  
Mouse Pancreatic Islets

Abstract. The activity of cyclic AMP phosphodiesterase in mouse pancreatic islets was investigated. 85% of the total activity was found in a 27 000 g supernatant fraction. The phosphodiesterase activity in the supernatant fraction, but not in the particulate fraction, was stimulated approximately 20% by Ca2+ (10−5m) and calmodulin (1 μm). The Km (cyclic AMP) of the unstimulated enzyme in the supernatant fraction was 20 μm, and the Vmax was 2 nmol/min × mg protein−1. The possible influence of a range of phospholipids was investigated. PI* and PS (150 μg/ml) inhibited the enzyme 20–30% both in the absence and presence of Ca2+/calmodulin, whereas PE, PC and PA did not affect the enzyme activity. ATP (1 mm) did not affect the particulate or supernatant fraction phosphodiesterase either in the absence or presence of Ca2+/calmodulin or Ca2+/phospholipid. It is concluded that, contrary to islet adenylate cyclase, islet cyclic AMP phosphodiesterase may be regulated by Ca2+/calmodulin.

scholarly journals Ciliary neurotrophic factor promotes survival of neonatal rat islets via the BCL-2 anti-apoptotic pathway

2007 ◽  
Vol 195 (1) ◽  
pp. 157-165 ◽  
Author(s):  
Luiz F Rezende ◽  
Luiz F Stoppiglia ◽  
Kleber L A Souza ◽  
Alessandro Negro ◽  
Francesco Langone ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Glucose Metabolism ◽  
Pancreatic Islets ◽  
Neurotrophic Factor ◽  
Caspase 3 ◽  
Ciliary Neurotrophic Factor ◽  
Neonatal Rat ◽  
Secretory Process ◽  
Apoptotic Pathway ◽  
Isolated Pancreatic Islets

Ciliary neurotrophic factor (CNTF) belongs to the cytokine family and increases neuron differentiation and/or survival. Pancreatic islets are richly innervated and express receptors for nerve growth factors (NGFs) and may undergo neurotypic responses. CNTF is found in pancreatic islets and exerts paracrine effects in neighboring cells. The aim of this study was to investigate possible effects of CNTF on neonatal rat pancreatic islet differentiation and/or survival. For this purpose, we isolated pancreatic islets from neonatal rats (1–2 days old) by the collagenase method and cultured for 3 days in RPMI medium with (CNTF) or without (CTL) 1 nM CNTF. Thereafter, glucose-stimulated insulin secretion (RIA), general metabolism by (NAD(P)H production; MTS), glucose metabolism (14CO2 production), gene (RT-PCR), protein expression (western blotting), caspase-3 activity (Asp–Glu–Val–Asp (DEVD)), and apoptosis (DNA fragmentation) were analyzed. Our results showed that CNTF-treated islets demonstrated reduced glucose-induced insulin secretion. CNTF treatment did not affect glucose metabolism, as well as the expression of mRNAs and proteins that are crucial for the secretory process. Conversely, CNTF significantly increased mRNA and protein levels related to cell survival, such as Cx36, PAX4, and BCL-2, reduced caspase-3 activity, and islet cells apoptosis, suggesting that CNTF does not affect islet cell differentiation and, instead, acts as a survival factor reducing apoptosis by increasing the expression of the anti-apoptotic BCL-2 protein and decreasing caspase-3 activity.

Insulin production and glucose metabolism in isolated pancreatic islets of rats with NIDDM

Diabetes ◽  
1988 ◽  
Vol 37 (9) ◽  
pp. 1226-1233 ◽  
Author(s):  
B. Portha ◽  
M. H. Giroix ◽  
P. Serradas ◽  
N. Welsh ◽  
C. Hellerstrom ◽  
...  
Keyword(s):  
Glucose Metabolism ◽  
Pancreatic Islets ◽  
Insulin Production ◽  
Isolated Pancreatic Islets

scholarly journals The effect of starvation on insulin secretion and glucose metabolism in mouse pancreatic islets

1974 ◽  
Vol 140 (3) ◽  
pp. 423-433 ◽  
Author(s):  
Carl J. Hedeskov ◽  
Kirsten Capito
Keyword(s):  
Insulin Secretion ◽  
Glucose Metabolism ◽  
Pancreatic Islets ◽  
Glucose Utilization ◽  
Secretory Response ◽  
Secretory Process ◽  
Fed State ◽  
Lactate Output ◽  
Extracellular Glucose ◽  
Km Value

1. Rates of insulin secretion, glucose utilization, lactate output, incorporation of glucose into glycogen, contents of glucose 6-phosphate, fructose 1,6-diphosphate and ATP, and maximally extractable enzyme activities of hexokinase, high-Km glucose-phosphorylating activity (`glucokinase'), glucose 6-phosphatase and unspecific acid phosphatase were measured in isolated pancreatic islets from fed and 48-h-starved mice. 2. In the fed state insulin secretion from isolated islets was increased five- to six-fold when the extracellular glucose concentration was raised from 2.5mm to 16.7mm; 5mm-caffeine potentiated this effect. The secretory response to glucose of islets from mice starved for 48h was diminished at all glucose concentrations from 2.5mm up to approx. 40mm. Very high glucose concentrations (60mm and above) restored the secretory response to that found in the fed state, suggesting that the Km value for the overall secretory process had been increased (approx. fourfold) by starvation. Addition of 5mm-caffeine to islets from starved mice also restored the insulin secretory response to 2.5–16.7mm-glucose to normal values. 3. Extractable hexokinase, `glucokinase', glucose 6-phosphatase and unspecific phosphatase activities were not changed by starvation. 4. Glucose utilization and glycolysis (measured as the rate of formation of 3H2O from [5-3H]glucose over a 2h period) was decreased in islets from starved mice at all glucose concentrations up to approx. 55mm. At still higher glucose concentrations up to approx. 100mm, there was no difference between the fed and starved state, suggesting that the Km value for the rate-limiting glucose phosphorylation had been increased (approx. twofold) by starvation. Preparation of islets omitting substrates (glucose, pyruvate, fumarate and glutamate) from the medium during collagenase treatment lowered the glucose utilization measured subsequently at 16.7mm-glucose by 38 and 30% in islets from fed and starved mice respectively. Also the 2h lactate output by the islets at 16.7mm extracellular glucose was diminished by starvation. Incorporation of glucose into glycogen was extremely low, but the rate of incorporation was more than doubled by starvation. 5. After incubation for 30min at 16.7mm-glucose the content of glucose 6-phosphate was unchanged by starvation, that of ATP was increased and the concentration of (fructose 1,6-diphosphate plus triose phosphates) was decreased. 6. Possible mechanisms behind the correlated impairment in insulin secretion and islet glucose metabolism during starvation are discussed.

Insulin Production and Glucose Metabolism in Isolated Pancreatic Islets of Rats With NIDDM

Diabetes ◽  
1988 ◽  
Vol 37 (9) ◽  
pp. 1226-1233 ◽  
Author(s):  
B. Portha ◽  
M.-H. Giroix ◽  
P. Serradas ◽  
N. Welsh ◽  
C. Hellerstrom ◽  
...  
Keyword(s):  
Glucose Metabolism ◽  
Pancreatic Islets ◽  
Insulin Production ◽  
Isolated Pancreatic Islets

scholarly journals Stimulation by glucose of cyclic AMP accumulation in mouse pancreatic islets is mediated by protein kinase C

1988 ◽  
Vol 253 (1) ◽  
pp. 229-234 ◽  
Author(s):  
P Thams ◽  
K Capito ◽  
C J Hedeskov
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Cyclic Amp ◽  
Adenylate Cyclase ◽  
Pancreatic Islets ◽  
Time Course ◽  
Ionophore A23187 ◽  
Kinase C ◽  
Cyclic Amp Accumulation ◽  
Mouse Pancreatic Islets

The mechanism of glucose-stimulated cyclic AMP accumulation in mouse pancreatic islets was studied. In the presence of 3-isobutyl-1-methylxanthine, both glucose and the phorbol ester 12-O-tetradecanoylphorbol 13-acetate (TPA), an activator of protein kinase C, enhanced cyclic AMP formation 2.5-fold during 60 min of incubation. Both TPA-stimulated and glucose-stimulated cyclic AMP accumulations were abolished by the omission of extracellular Ca2+. The Ca2+ ionophore A23187 did not affect cyclic AMP accumulation itself, but affected the time course of TPA-induced cyclic AMP accumulation, the effect of A23187 + TPA mimicking the time course for glucose-induced cyclic AMP accumulation. A 24 h exposure to TPA, which depletes islets of protein kinase C, abolished the effects of both TPA and glucose on cyclic AMP production. Both TPA-induced and glucose-induced cyclic AMP productions were inhibited by anti-glucagon antibody, and after pretreatment with this antibody glucose stimulation was dependent on addition of glucagon. Pretreatment of islets with TPA for 10 min potentiated glucagon stimulation and impaired somatostatin inhibition of adenylate cyclase activity in a particulate fraction of islets. Carbamoylcholine, which is supposed to activate protein kinase C in islets, likewise stimulated cyclic AMP accumulation in islets. These observations suggest that glucose stimulates islet adenylate cyclase by activation of protein kinase C, and thereby potentiates the effect of endogenous glucagon on adenylate cyclase.

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