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Biomedical subjects

S L Howell

Publications and source records attributed to S L Howell.

At least 91 records · Page 5Linked to original sources
PubMed1981

Cell replication in the islets of langerhans of adult rats: effects of pregnancy, ovariectomy and treatment with steroid hormones.

It was possible to vary the replication rate of cells in the islets of Langerhans of adult rats. The rate of incorporation of [3H]thymidine into islet DNA was increased at 12 days of pregnancy to 2.3-fold and at 19 days of pregnancy to 1.3-fold that in control rats. Ovariectomy, which leads to lowered plasma levels of ovarian steroids, induced a significant and unexpected increase in the rate of thymidine incorporation into islets; treatment of ovariectomized rats with 2 micrograms oestradiol/rat per day for 3 days reversed this upward trend. When islets from normal rats were cultured with certain combinations of steroid hormones including progesterone and oestradiol or with insulin secretagogues, with the exception of glucose, a decreased rate of DNA synthesis was usually found compared with that in control rats. Since treatment with steroid hormones inhibited incorporation of [3H]thymidine into islets from ovariectomized rats and directly reduced incorporation into tissue-cultured islets from normal rats in vitro, it was concluded that increased levels of steroid hormones were not responsible for the higher rate of regeneration of islet cells in pregnant rats. However, a striking correlation between levels of blood glucose in vivo and DNA synthesis in islets in vitro has been observed.

Animals↗
PubMed1980

Regulation of actin polymerizaton in rat islets of Langerhans.

A DNAase-inhibition assay was used to determine the proportions of globular (G-) and filamentous (F-) actin in islets of Langerhans after incubation in various conditions, or after subcellular fractionation. Stimulation of insulin secretion resulted in an ATP-dependent increase in the proportion of F-actin present; fractionation showed 80-90% of the actin to be present in the final supernatant.

1-Methyl-3-isobutylxanthine↗
PubMed1980

Problems in the use of polycarbonate diffusion chambers for syngeneic pancreatic islet transplantation in rats.

Islets of Langerhans have been enclosed in polycarbonate diffusion chambers and transplanted intraperitoneally to syngeneic streptozotocin diabetic rats. Direct implantation of 1100--1400 islets in these chambers failed to reverse diabetes during a period of 12 weeks, and viable islet tissue was not recoverable at the end of this period. Islets placed in chambers which had been implanted 3--12 weeks previously similarly failed to lower blood glucose of diabetic recipients, as a result of lack of survival of the islets. Insulin infusion into chambers previously implanted in vivo, I125 insulin diffusion studies in chambers recovered 6--8 weeks after implantation, and scanning electron microscopy of the recovered membranes all indicated that the pores were not totally occluded. The failure of islet transplantation via chambers in this simple syngeneic model has discouraging implications for their use as a means of avoiding allograft rejection.

Animals↗
PubMed1980

The role of actin in the secretory cycle.

Binding of filamentous actin to isolated insulin storage granules has been demonstrated in an in vitro system; this binding is enhanced by 2 mM ATP, but is diminished in the presence of 1 mM CaCl2. It is unaffected by glucose or by cyclic AMP. Estimation of the actin content of isolated rat islets by DNAase inhibition indicates that G-actin constitutes 1 to 2% of the protein content of the islets, that 50 to 70% of the actin content of the islets is present as the depolymerized globular from (G-actin), and that the proportion of F-actin found may be increased in islets incubated in the presence of 20mM glucose. Thus both the proportions of G- and F-actin, and the binding of granules to F-actin may be important in the regulation of rates of insulin secretion.

Actins↗
PubMed1979

Interaction between insulin-storage granules and F-actin in vitro.

Possible interactions between polymerized (F-) actin and insulin-storage granules from rat islets of Langerhans were examined in vitro by comparing the sedimentation of the granules in the presence of various actin concentrations. Actin in the concentration range 0.1--0.5 mg/ml produced a retardation in granule-sedimentation rates consistent with binding of the granules to the actin filaments. The interaction was increased by addition of ATP (2mM), but was decreased by CaCl2 (0.1 mM). Binding of granules to actin was unaffected by cyclic AMP or by preincubation of the granules with phospholipase C. Specificity of the interaction was confirmed by the use of depolymerized (G-) actin and of myosin to provide a solution of comparable viscosity; neither of these caused any alteration of granule sedimentation. Possible implications of this interaction of insulin-storage granules with actin for the mechanism of insulin secretion are briefly discussed.

Actins↗
PubMed1979

Preservation of the effects of pregnancy on rat islets of Langerhans in tissue culture.

Islets of Langerhans, isolated from normal or 19-day pregnant rats, were cultured for 20 h at 37 degrees C in tissue culture medium 199. When islets were cultured in medium containing low glucose (5.5 mM), the higher adenylate cyclase activity and insulin secretory responses characteristic of islets from pregnant rats were maintained during the test period of 29 h. Islets from normal and pregnant rats were also cultured for 20 h in medium containing a very high glucose concentration (83.3 mM) in order to load the B cells with glycogen. It was found, after glycogen loading, that, while adenylate cyclase activity increased to a greater extent in islets from pregnant rats than controls, this activity was not increased in proportion to the striking changes in insulin release rate observed in pregnant rat islets. The results show that the difference in insulin secretory response between islets from normal and pregnant rats may be preserved when the islets are cultured for 20 h, and that these differences are enhanced for a variety of reasons after culture of islets in 83.3 mM glucose.

Adenylyl Cyclases↗
PubMed1978

Role of microtubules in the intracellular transport of growth hormone.

Pulse-chase experiments utilising (3H)leucine have been used to study the effects of colchicine and vinblastine on intracellular transport and secretion of newly synthesised growth hormone from rat anterior pituitary fragments. Growth hormone was isolated from medium and fragments by polyacrylamide gel electrophoresis. When colchicine or vinblastine, which disrupt microtubules, were added immediately after pulse labelling, inhibition of the subsequent secretion of newly synthesised growth hormone was detected throughout the succeeding 5h. Similar inhibition was seen if the drugs were added after a 1h delay. However, if colchicine or vinblastine were added only after a 2h chase incubation, then no significant effect on subsequent release of labelled growth hormone was seen. The results suggest that these agents may inhibit the transport of newly formed growth hormone storage granules from the Golgi complex to the cytoplasmic pool. Microtubules do not appear to be involved in the mechanism of the final secretion of newly synthesised hormone by exocytosis.

Animals↗
PubMed1977

Alterations in regulation of insulin biosynthesis in pregnancy and starvation studied in isolated rat islets of langerhans.

1. Insulin biosynthesis in isolated rat islets of Langerhans was determined by the incorporation of [(3)H]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 [(3)H]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 beta-cell function.

Animals↗