Evidence against the involvement of cyclic GMP in the insulin-stimulation of lipoprotein lipase activity in fat cells

Summary Under in vitro experimental conditions in which insulin increases adipose tissue lipoprotein lipase, cyclic GMP or dibutyryl cyclic GMP has no effect on this enzyme in rat adipose tissue fragments, or on either the intra- or extracellular forms of this enzyme in isolated fat cells. These results do not support the involvement of cyclic GMP in the insulin-stimulation of lipoprotein lipase in adipose tissue.Acknowledgments. This work was supported by grants from the Institut National de la Santé et de la Recherche Médicale (INSERM), the Université René Descartes (Paris V) and the École Pratique des Hautes-Etudes (3e Section).     

Metabolic activity of adipose tissue in the goat during gestation and at the beginning of lactation]

In 5 French Alpine goats, omental adipose tissue acetyl-CoA carboxylase, glucose-6-phosphate deshydrogenase, malic enzyme and lipoprotein lipase activities significantly decreased during the third month of gestation, whereas plasma non-esterified fatty acid and triacyglycerol contents increased. This probably reflects an early decreasing rate of adipose tissue anabolism during gestation in the Goat. At the third week of lactation, anabolic activities relative to DNA content of adipose tissue were extremely low, and the tissue weight relative to DNA was lower than during gestation. Metabolic alterations of omental adipose tissue in early lactation do not seem to be related to milk production level. These results could contribute to a better control of the kinetic of body lipid stores during the reproductive cycle in high milk yielding ruminants.     

Changes in mammary tissue lipid metabolism in the goats during the first 2 months of lactation]

5 French Alpine Goats were studied after normal or premature parturition. Mammary tissue acetyl-C oA carboxylase, glucose-6-phosphate dehydrogenase, malic enzyme and lipoprotein lipase (LPL) activities varied in parallel with milk fat secretion from the 3rd to the 9th week of lactation. Variations of mammary LPL activity and of long chain fatty acid secretion were positively highly correlated during that period. In goats with normal parturition, lipogenic activities seemed to reach a maximum level shortly after parturition. There was a positive correlation between mammary Ll activities and plasma non esterified fatty acid contents, possibly reflecting a relationship between adipose tissue mobilisation and mammary metabolism.     

Metabolic activity of goat adipose tissue at the end of gestation and at the beginning of lactation: level of deoxyribouncleic acid content and lipoprotein lipase activity]

In the goat the passage from late pregnancy to early lactation is accompanied by a decrease of the epiploon lipoprotein lipase activity and an increase in the epiploon DNA content. The between-goat variations allow us to emphasize a linear relation between the lipoprotein lipase activity decrease and the reduction of the epiploon volume, expressed on a DNA basis. These parameters, used as indicators of the adipose tissue metabolic status, could contribue to the determination of a feeding strategy adapted to high yield milking Ruminants.     

The response of cyclic 3',5'-AMP and cyclic 3',5'-GMP phosphodiesterases to experimental diabetes

Alloxan diabetes caused a decrease in cyclic AMP phosphodiesterase in all affected rat tissues. Cyclic GMP phosphodiesterase activity was, however, decreased in adipose and liver, but increased increased in heart and uterus.     

Plasma cyclic 3',5'-guanosine monophosphate and cyclic 3',5'-adenosine monophosphate response to methacholine in man

Cholinergic agents are known to induce increases in tissue and plasma levels of cyclic GMP in experimental animals. We observed that i.m. injection of methacholine, a cholinergic agent, caused significant increases in plasma cyclic GMP and cyclic AMP in man.     

Plasma cyclic 3′,5′-guanosine monophosphate and cyclic 3′,5′-adenosine monophosphate response to methacholine in man

Summary Cholinergic agents are known to induce increases in tissue and plasma levels of cyclic GMP in experimental animals. We observed that i.m. injection of methacholine, a cholinergic agent, caused significant increases in plasma cyclic GMP and cyclic AMP in man.     

The response of cyclic 3′,5′-AMP and cyclic 3′,5′-GMP phosphodiesterases to experimental diabetes

Summary Alloxan diabetes caused a decrease in cyclic AMP phosphodiesterase in all affected rat tissues. Cyclic GMP phosphodiesterase activity was, however, decreased in adipose and liver, but increased in heart and uterus.This research was supported by U.S. Public Health Service grant RO1-AM19364-O1 and MARC training grant No. 1-TO2-GMO50000.     

Absence of effects of dibutyryl cyclic guanosine 3',5'-monophosphate on release of alpha-amylase, 45Ca efflux, and protein synthesis in rat pancreas in vitro.

Dibutyryl cyclic GMP did not affect basal, or carbachol stimulated secretion of alpha-amylase from rat pancreas. The nucleotide did not have a significant effect on 45Ca release from the pancreas nor did it alter the response to carbachol. The dibutyryl analogue of cyclic GMP did not duplicate or alter the inhibitory effect of carbachol on 3H-leucine incorporation into pancreatic trichloroacetic acid-precipitable protein.     

Increased urinary excretion of cyclic nucleotides in X-linked hypophosphatemic (Hyp) mice

Hyp mice, a model for human X-linked hypophosphatemia, had elevated urinary cyclic AMP, cyclic GMP, and magnesium excretion compared to normal mice. The data suggest a renal origin of the urinary cyclic nucleotides. No significant differences in plasma cyclic AMP and cyclic GMP were observed between genotypes.     

Cyclic nucleotide levels in the perfused rat heart subjected to hypoxia.

Isolated rat hearts were subjected to hypoxic perfusion on a recirculating Langendorff apparatus. Following a 30-min-period of aerobic stabilization the hearts were perfused for 30 min with media equilibrated with 84% N2, 12%O2 and 4% CO2. At the end of the hypoxic period myocardial concentrations of cyclic AMP and cyclic GMP were determined by radioimmunoassay. Exposure to hypoxia resulted in a significant increase in cyclic AMP (p less than 0.01) and a decrease in cyclic GMP (p less than 0.05) as compared to hearts perfused for 60 min with media gassed with 96% O2. 4% CO2.     

Effect of AD6 (8-monochloro-3-beta-diethylamino-ethyl-4-methyl-7-ethoxycarbonylmethoxy coumarin) on cyclic nucleotide phosphodiesterases in human platelets

Summary The effect of AD6 (8-monochloro-3-beta-diethylamino-ethyl-4-methyl-7-ethoxycarbonylmethoxy coumarin), an inhibitor of platelet aggregation, on cyclic nucleotide metabolism was investigated. AD6 inhibited selectively human platelet cyclic GMP phosphodiesterase, which was separated from cyclic AMP phosphodiesterase by DEAE-cellulose chromatography. Addition of AD6 to washed platelets increased cyclic GMP levels significantly in two minutes. These results could be useful in elucidating the action of AD6 on intact platelets.     

Effect of AD6 (8-monochloro-3-beta-diethylamino-ethyl-4-methyl-7-ethoxycarbonylme tho xy coumarin) on cyclic nucleotide phosphodiesterases in human platelets

The effect of AD6 (8-monochloro-3-beta-diethylamino-ethyl-4-methyl-7-ethoxycarbonylmeth oxy coumarin), an inhibitor of platelet aggregation, on cyclic nucleotide metabolism was investigated. AD6 inhibited selectively human platelet cyclic GMP phosphodiesterase, which was separated from cyclic AMP phosphodiesterase by DEAE-cellulose chromatography. Addition of AD6 to washed platelets increased cyclic GMP levels significantly in two minutes. These results could be useful in elucidating the action of AD6 on intact platelets.     

Increased urinary excretion of cyclic nucleotides in X-linked hypophosphatemic (Hyp) mice

Summary Hyp mice, a model for human X-linked hypophosphatemia, had elevated urinary cyclic AMP, cyclic GMP, and magnesium excretion compared to normal mice. The data suggest a renal origin of the urinary cyclic nucleotides. No significant differences in plasma cyclic AMP and cyclic GMP were observed between genotypes.This work was supported in part by research grants from The Kroc Foundation and the NIH, RR-09016.     

Decreased cyclic GMP levels in rat cecum mucosa during adaptive stimulation of Na-K-ATPase.

In rat cecal mucosa, Na-K-ATPase specific activity and sodium and fluid absorption were increased by giving polyethylene glycol administration with the drinking water. Whereas cyclic AMP levels were unchanged, cyclic GMP was reduced by about 50%. This finding suggests a regulatory role of cyclic GMP in intestinal sodium and fluid absorption.     

Variations of cyclic nucleotide monophosphate levels during spontaneous uterine contractions.

Oscillations on the concentrations of cyclic nucliotides occurred during spontaneous rhythmic contractions in rat uterus. The levels of cyclic GMP and cyclic AMP were highest at the beginning of the contraction respectively the relaxation.     

Cyclic nucleotide levels in the perfused rat heart subjected to hypoxia

Summary Isolated rat hearts were subjected to hypoxic perfusion on a recirculating Langendorff apparatus. Following a 30-min-period of aerobic stabilization the hearts were perfused for 30 min with media equilibrated with 84% N₂, 12% O₂ and 4% CO₂. At the end of the hypoxic period myocardial concentrations of cyclic AMP and cyclic GMP were determined by radioimmunoassay. Exposure to hypoxia resulted in a significant increase in cyclic AMP (p<0.01) and a decrease in cyclic GMP (p<0.05) as compared to hearts perfused for 60 min with media gassed with 96% O₂, 4% CO₂.Acknowledgment. We gratefully acknowledge the excellent technical assistance provided by Mrs Inger O. Boggs and Miss Patricia C. Hannigan. This work was supported in part by U. S. Public Health Service grant HL 14661 from the National Heart and Lung Institute, and by a grant from the Central Ohio Heart Chapter.     

Regulation of calcitonin release from the 6.23 rat C-cell line by cyclic nucleotide analogues and pharmacological mediators.

Calcitonin release from 6.23 rat medullary thyroid carcinoma C-cells was stimulated by dibutyryl cyclic AMP and inhibited by dibutyryl cyclic GMP in concentration dependent fashion. Histamine, isoproterenol, prostaglandin E2 and Bay K 8644 stimulated calcitonin release, while acetylcholine and serotonin had no significant effect on CT release.     

Effect of vinblastine on pancreatic enzymes secretion induced by cyclic nucleotide derivatives.

Vinblastine did not affect the basal secretion of enzymes from the rat pancreas, but it potentiates the secretory response to dibutyryl cyclic AMP. This potentiation is confirmed by the observation of numerous pictures of exocytosis at the apical part of the acinar cell. Dibutyryl cyclic GMP by itself, or associated with vinblastine, failed to modify the spontaneous release of enzymes or the secretion induced by dibutyryl cyclic AMP.