scholarly journals Regulation of insulin release from isolated islets of Langerhans of the rat in pregnancy. The role of adenosine 3′:5′-cyclic monophosphate

1973 ◽  
Vol 134 (2) ◽  
pp. 481-487 ◽  
Author(s):  
I. C. Green ◽  
S. L. Howell ◽  
W. Montague ◽  
K. W. Taylor
Keyword(s):  
Insulin Secretion ◽  
Protein Kinase ◽  
Cyclic Amp ◽  
Islets Of Langerhans ◽  
Kinase Activity ◽  
Protein Kinase Activity ◽  
Normal Female ◽  
Pregnant Rats ◽  
Isolated Islets Of Langerhans ◽  
In Pregnancy

1. The concentrations of cyclic AMP were compared in islets of Langerhans isolated from the pancreases of normal female and pregnant rats and were higher in islets in pregnancy. 2. There was also a significant increase in adenylate cyclase activity in homogenates of islets from pregnant rats compared with those from normal rats. 3. Increased cyclic AMP concentration in islets from pregnant rats was reflected in increased protein kinase activity. When the cyclic AMP-dependent protein kinase activity was increased by 3-isobutyl-1-methylxanthine this stimulated activity was significantly greater in pregnancy. 4. Insulin-secretion studies with islets from normal and pregnant rats showed that theophylline or 3-isobutyl-1-methylxanthine, which raise intracellular cyclic AMP concentrations, caused a significantly greater insulin secretion in pregnancy. 5. It was also found that in the presence of a glucose concentration too low to stimulate insulin secretion, the latter could be induced if the cyclic AMP concentrations were raised sufficiently with 3-isobutyl-1-methylxanthine. 6. It is suggested that the higher cyclic AMP concentrations observed in islets in pregnancy mediate the greater insulin-secretory capacity, as well as the greater sensitivity of these islets to low glucose concentrations.

INSULIN SECRETORY RESPONSE OF ISOLATED ISLETS OF LANGERHANS IN PREGNANT RATS: EFFECTS OF DIETARY RESTRICTION

1974 ◽  
Vol 62 (1) ◽  
pp. 137-143 ◽  
Author(s):  
I. C. GREEN ◽  
K. W. TAYLOR
Keyword(s):  
Insulin Secretion ◽  
Food Intake ◽  
Islets Of Langerhans ◽  
Secretory Response ◽  
Pregnant Rats ◽  
Additional Food ◽  
Daily Food ◽  
Isolated Islets Of Langerhans ◽  
Low Glucose ◽  
In Pregnancy

SUMMARY The effects of diet on the altered insulin secretory responses of islets of Langerhans of pregnant rats have been investigated. The daily food intake of pregnant rats was found to exceed that of control non-pregnant rats by 20% on average. Depriving pregnant rats of this additional food resulted in an alteration in the pattern of insulin secretion seen in pregnancy, such that the sensitivity to stimulation by low glucose concentrations was abolished. The contribution made by different components of the diet to the secretory response in pregnancy was investigated. When additional carbohydrate, though not protein, was fed to pregnant rats on a restricted food intake, the sensitivity of the islets to glucose stimulation was restored. It was concluded that the quantity and in particular the carbohydrate content of food eaten by pregnant rats exerts an important influence on the changes in insulin secretion in pregnancy.

scholarly journals Alterations in regulation of insulin biosynthesis in pregnancy and starvation studied in isolated rat islets of Langerhans

1977 ◽  
Vol 166 (3) ◽  
pp. 501-507 ◽  
Author(s):  
Adrian J. Bone ◽  
Simon L. Howell
Keyword(s):  
Cyclic Amp ◽  
Islets Of Langerhans ◽  
Insulin Biosynthesis ◽  
Normal Female ◽  
Pregnant Rats ◽  
Rat Islets ◽  
Isolated Rat Islets ◽  
Rat Islets Of Langerhans ◽  
Isolated Rat ◽  
In Pregnancy

1. Insulin biosynthesis in isolated rat islets of Langerhans was determined by the incorporation of [3H]leucine into newly synthesized islet proteins. Anti-insulin serum covalently coupled to a solid phase (CNBr-activated Sepharose 4B) was used to separate the immunoreactive proinsulin and insulin from other islet proteins. This method was applied to a study of the regulation of insulin biosynthesis in isolated rat islets of Langerhans during pregnancy, and immediately after a period of food deprivation. 2. Islets isolated from pregnant rats showed an increased basal rate of synthesis compared with the non-pregnant controls. In addition, they showed a significant increase in biosynthesis of proinsulin and insulin in comparison with the normal islets over a range of glucose concentrations of 2–20mm. 3. Addition of the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine significantly increased the insulin-synthetic response of normal islets over the glucose range 5–20mm, so that their glucose response approached that of islets from pregnant rats. 4. Normal female rates were injected with a long-acting progesterone derivative (hydroxyprogesterone hexanoate), to investigate the role of progesterone on the increased insulin biosynthesis observed in islets in pregnancy. There appeared to be no marked difference in insulin biosynthesis between the islets from the progesterone-injected and control rats in the presence of 2mm- or 6mm-glucose alone. However, in the presence of 4mm- or 6mm-glucose and 3-isobutyl-1-methylxanthine there was a significant increase in insulin biosynthesis in the progesterone-treated animals. 5. Total islet protein biosynthesis was determined by the incorporation of [3H]leucine into trichloroacetic acid-precipitable islet proteins. Islets isolated from normal rats showed a 1.6-fold increase in incorporation over the glucose concentration range 2–20mm, and this value remained unchanged during starvation; however, rates of incorporation were significantly raised in islets isolated from pregnant rats in the presence of 20mm-glucose. 6. Islets from starved and fed control rats were incubated in the presence of increasing concentrations of glucose or glucose+3-isobutyl-1-methylxanthine. The islets isolated from the starved animals showed a diminished insulin-synthetic response to glucose as compared with the controls; this response was partially restored to normal values by elevation of cyclic AMP concentrations by using 3-isobutyl-1-methylxanthine. 7. It is suggested that the alterations in glucose-stimulated insulin biosynthesis observed in islets during pregnancy and after a period of starvation could be attributable, at least in part, to a long-term alteration of the cyclic AMP system, and in pregnancy to a direct or indirect effect of progesterone on β-cell function.

scholarly journals The mode of action of adenosine 3′:5′-cyclic monophosphate in mammalian islets of Langerhans. Effects of insulin secretagogues on islet-cell protein kinase activity

1973 ◽  
Vol 134 (1) ◽  
pp. 321-327 ◽  
Author(s):  
W. Montague ◽  
S. L. Howell
Keyword(s):  
Insulin Secretion ◽  
Protein Kinase ◽  
Cyclic Amp ◽  
Insulin Release ◽  
Glucose Concentration ◽  
Incubation Medium ◽  
Kinase Activity ◽  
Islet Cells ◽  
Protein Kinase Activity ◽  
Stimulate Insulin Release

1. Protein kinase activity was measured in islets of Langerhans that had been incubated in the presence of agents known to affect insulin release. 2. Glucagon, theophylline, caffeine and 3-isobutyl-1-methylxanthine, agents that raise cyclic AMP concentrations in islet cells and stimulate insulin release, increased protein kinase activity. Adrenaline and diazoxide, agents that decrease cyclic AMP concentrations and inhibit insulin secretion, decreased the activity. 3. The increase in protein kinase activity produced by different concentrations of 3-isobutyl-1-methylxanthine was apparently related to the increase in intracellular concentrations of cyclic AMP. 4. The sulphonylureas, tolbutamide and glibenclamide, agents that increase insulin release, also increased the protein kinase activity; however, leucine, arginine and xylitol, which also stimulate insulin release, were without effect on the kinase activity. 5. Increasing the glucose concentration of the incubation medium from 2 to 20mm had no effect on protein kinase activity. Further, the ability of 3-isobutyl-1-methylxanthine to increase the protein kinase activity was not affected by the glucose concentration of the incubation medium. 6. These results suggest that agents which affect insulin secretion by altering cyclic AMP concentrations may exert their effects on hormone release by altering the activity of a cyclic AMP-dependent protein kinase in islet cells.

EFFECT OF PROGESTERONE ON INSULIN SECRETION IN THE RAT

1978 ◽  
Vol 76 (3) ◽  
pp. 479-486 ◽  
Author(s):  
J. P. ASHBY ◽  
D. SHIRLING ◽  
J. D. BAIRD
Keyword(s):  
Insulin Secretion ◽  
Cyclic Amp ◽  
Islets Of Langerhans ◽  
Isolated Islets ◽  
Β Cell ◽  
Insulin In Plasma ◽  
Isolated Islets Of Langerhans ◽  
Low Concentrations ◽  
In Pregnancy

Implants of progesterone resulted in an increased amount of insulin in plasma in response to intravenous administration of glucose in the rat. Isolated islets of Langerhans from progesterone-treated animals showed a greater maximum secretory response to glucose than islets from control animals but their sensitivity to low concentrations of glucose was unchanged. Theophylline increased glucose-induced secretion of insulin to a greater extent in progesterone-treated than in control rats and also produced a greater increase in the concentration of cyclic AMP in isolated islets from hormone-treated animals. These results suggest that the effect of progesterone on insulin secretion may be mediated by a change in cyclic AMP levels in the β cell. The possible role of progesterone in increasing the secretion of insulin in pregnancy is discussed.

scholarly journals Correlation of Ca2+-and calmodulin-dependent protein kinase activity with secretion of insulin from islets of Langerhans

1983 ◽  
Vol 212 (3) ◽  
pp. 819-827 ◽  
Author(s):  
J R Colca ◽  
C L Brooks ◽  
M Landt ◽  
M L McDaniel
Keyword(s):  
Insulin Secretion ◽  
Protein Kinase ◽  
Islets Of Langerhans ◽  
Kinase Activity ◽  
Islet Cells ◽  
Protein Kinase Activity ◽  
Dependent Protein Kinase ◽  
Dependent Protein ◽  
Endogenous Substrates ◽  
Endogenous Proteins

A Ca2+-activated and calmodulin-dependent protein kinase activity which phosphorylates predominantly two endogenous proteins of 57kDa and 54kDa was found in a microsomal fraction from islet cells. Half-maximal activation of the protein kinase occurs at approx. 1.9 microM-Ca2+ and 4 micrograms of calmodulin/ml (250 nM) for phosphorylation of both protein substrates. Similar phosphoprotein bands (57kDa and 54kDa) were identified in intact islets that had been labelled with [32P]Pi. Islets prelabelled with [32P]Pi and incubated with 28 mM-glucose secreted significantly more insulin and had greater incorporation of radioactivity into the 54 kDa protein than did islets incubated under basal conditions in the presence of 5 mM-glucose. Thus the potential importance of the phosphorylation of these proteins in the regulation of insulin secretion is indicated both by activation of the protein kinase activity by physiological concentrations of free Ca2+ and by correlation of the phosphorylation of the substrates with insulin secretion in intact islets. Experiments undertaken to identify the endogenous substrates indicated that this calmodulin-dependent protein kinase may phosphorylate the alpha- and β-subunits of tubulin. These findings suggest that Ca2+-stimulated phosphorylation of islet-cell tubulin via a membrane-bound calmodulin-dependent protein kinase may represent a critical step in the initiation of insulin secretion from the islets of Langerhans.

scholarly journals Evidence for Ecto-Protein Kinase Activity That Phosphorylates Kemptide in a Cyclic AMP-dependent Mode

1989 ◽  
Vol 264 (24) ◽  
pp. 14549-14555 ◽  
Author(s):  
D Kübler ◽  
W Pyerin ◽  
O Bill ◽  
A Hotz ◽  
J Sonka ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Cyclic Amp ◽  
Kinase Activity ◽  
Protein Kinase Activity

Regulation of protein kinase by vasopressin in renal medulla in situ

1977 ◽  
Vol 232 (1) ◽  
pp. F50-F57
Author(s):  
T. P. Dousa ◽  
L. D. Barnes
Keyword(s):  
Protein Kinase ◽  
Cyclic Amp ◽  
Kinase Activity ◽  
Kinase Inhibitor ◽  
Renal Medulla ◽  
Protein Kinase Activity ◽  
Kinase Activation ◽  
Heat Stable ◽  
Protein Kinase Activation ◽  
Heat Stable Protein

Results of this study demonstrate that vasopressin activates protein kinase in intact renal medullary cells as detected by measurement of the (-cyclic AMP/+cyclic AMP) protein kinase activity ratios in freshly prepared tissue extracts (40,000 X g supernates) from bovine renal medullary slices. The activation of protein kinase was specific for vasopressin since parathyroid hormone, histamine, angiotensin II, or the inactive analog of vasopressin did not activate protein kinase. There was a direct correlation between the extent of protein kinase activation and the elevation in tissue levels of cyclic AMP elicited by increasing doses of vasopressin or with an increase in incubation time. The elevation of tissue cyclic AMP level and maximum activation of protein kinase reached maximum level at a vasopressin concentration of about 2 X 10(-9) M. Incubation of slices with vasopressin caused a dose-dependent decrease in the cyclic AMP-dependent protein kinase activity in the 40,000 X g supernate of homogenate from the renal medullary slices. This effect of vasopressin was specific for protein kinase since activity of lactate dehydrogenase or a specific [3H]colchicine-binding activity was not affected, and the decrease in the protein kinase was not due to the accumulation of a heat-stable protein kinase inhibitor. There was an increase in protein kinase was not due to the accumulation of a heat-stable protein kinase inhibitor. There was an increase in protein kinase activity extracted from 40,000 X g pellets of homogenate prepared from slices exposed to vasopressin. Results thus provide evidence that cyclic AMP-mediated protein kinase activation in the intact cells is an integral part of cellular response of the mammalian renal medulla to vasopressin.

scholarly journals The role of protein kinase activation in the control of steroidogenesis by adrenocorticotrophic hormone in the adrenal cortex

1973 ◽  
Vol 136 (4) ◽  
pp. 993-998 ◽  
Author(s):  
Malcolm C. Richardson ◽  
Dennis Schulster
Keyword(s):  
Protein Kinase ◽  
Cyclic Amp ◽  
Adrenal Cortex ◽  
Kinase Activity ◽  
Protein Kinase Activity ◽  
Adrenocorticotrophic Hormone ◽  
Dependent Protein Kinase ◽  
Kinase Activation ◽  
Protein Kinase Activation ◽  
Dependent Protein

A method has been developed for investigation of the effect of adrenocorticotrophic hormone (ACTH) on the state of activation of a cyclic AMP-dependent protein kinase within cells of the adrenal cortex. Enzyme activity was measured in terms of the quantity of32P transferred from [γ-32P]ATP to histone under conditions in which bound cyclic AMP did not dissociate from the regulatory subunit of the protein kinase ACTH (1×10-2i.u./ml) caused a rapid and complete activation of the cyclic AMP-dependent protein kinase activity within 2min of hormone addition to the isolated cells. In response to a range of ACTH concentrations a sigmoid log dose–response curve for protein kinase activation was obtained, with half-maximal stimulation attained at about 1×10-3i.u./ml. However, some low doses of ACTH that elicited a marked (but submaximal) steroidogenic response failed to cause a clear stimulation of protein kinase activity in isolated adrenal cells. Theophylline (2mm) potentiated the effect of ACTH on protein kinase activity. The results implicate an important role for protein kinase in ACTH action on the adrenocortical cell.

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