Oxytocin secretion is stimulated by changes in glucose metabolism.

Previous studies have shown that infusion of oxytocin into normal dogs increased plasma levels of insulin and glucagon. These responses were accompanied by increased rates of glucose production and overall glucose uptake. The purpose of the present study was to determine whether, conversely, changes in glucose metabolism would result in changes in oxytocin secretion.

Release of GPI-anchored membrane proteins by a cell-associated GPI-specific phospholipase D.

Although many glycosylphosphatidylinositol (GPI)-anchored proteins have been observed as soluble forms, the mechanisms by which they are released from the cell surface have not been demonstrated. We show here that a cell-associated GPI-specific phospholipase D (GPI-PLD) releases the GPI-anchored, complement regulatory protein decay-accelerating factor (DAF) from HeLa cells, as well as the basic fibroblast growth factor-binding heparan sulfate proteoglycan from bone marrow stromal cells. DAF found in the HeLa cell culture supernatants contained both [3H]ethanolamine and [3H]inositol, but not [3H]palmitic acid, whereas the soluble heparan sulfate proteoglycan present in bone marrow stromal cell culture supernatants contained [3H]ethanolamine.

Role of insulin and glucagon in oxytocin effects on glucose metabolism.

Oxytocin (OT) infusion in normal dogs increases plasma insulin and glucagon levels and increases rates of glucose production and uptake. The purpose of this study was to determine whether the effects of OT on glucose metabolism were direct or indirect. The studies were carried out in normal, unanesthetized dogs in which OT infusion was superimposed on infusion of either somatostatin, which suppresses insulin and glucagon secretion, or clonidine, which suppresses insulin secretion only.

The metabolic effects of oxytocin are mediated by a uterine type of receptor and are inhibited by oxytocin antagonist and by arginine vasopressin in the dog.

Infusion of oxytocin (OT) into normal dogs, in doses which produced plasma levels of OT in the physiological range, has been shown to increase plasma levels of glucose, insulin and glucagon and increase rates of glucose production and uptake. This study sought to determine whether there was a correlation between these metabolic effects and the oxytocic potency of four less potent oxytocic analogues when infused into normal dogs. The rank order of oxytocic potency of all 4 correlated well with the rise in plasma glucose levels, and in 3 of the 4 with the rise in plasma insulin levels.

Production of the glycosylphosphatidylinositol-specific phospholipase D by the islets of Langerhans.

A large number of diverse cell surface proteins are anchored to the cell membrane by a glycosylphosphatidylinositol (GPI) anchor. One proposed function for the GPI anchor is that it facilitates the release of the protein from the cell by acting as a target for anchor-specific phospholipases. We and others have discovered that mammalian plasma contains a GPI-specific phospholipase D (GPI-PLD) (Cardoso de Almeida, M.

Effects of vasopressin on insulin secretion and inositol phosphate production in a hamster beta cell line (HIT).

The recent isolation of vasopressin (VP) from the rat and human pancreas led us to investigate the effects of VP on insulin secretion. In the SV 40-transformed hamster beta cell line (HIT), 0.1-1.

Effect of the fatty acid oxidation inhibitor methyl palmoxirate (methyl 2-tetradecylglycidate) on recovery from insulin-induced hypoglycemia in diabetic dogs.

Methyl palmoxirate, an effective hypoglycemic agent administered p.o., has been shown to decrease hepatic glucose production secondary to inhibition of mitochondrial fatty acid oxidation.

Relation of growth hormone and myocardial collagen accumulation in experimental diabetes.

A pathogenic role of growth hormone in the tissue complications of diabetes has been postulated. Because collagen has been found to accumulate in myocardial interstitium in diabetes, we have undertaken a study of the relationship of plasma growth hormone levels to collagen accumulation in a canine model of chronic diabetes. Sedentary normal animals and diabetic animals were compared respectively with physically conditioned animals in which the collagen increment associated with diabetes was minimized.

Growth hormone, insulin, glucose, cortisol, luteinizing hormone, and diabetes in beagle bitches treated with medroxyprogesterone acetate.

Adult beagle bitches (20 to 101 months old) received medroxyprogesterone acetate (MPA; 75 mg/kg, im) or control vehicle at 3 month intervals. Changes in serum concentrations of GH, insulin and glucose were determined in 18 MPA-treated and 6 of 12 control bitches at 0, 2, 4, 8, 16 and 17-24 months of treatment (Exp. I).

Oxytocin increases extrapancreatic glucagon secretion and glucose production in pancreatectomized dogs.

Infusion of oxytocin into normal dogs increases plasma levels of insulin and glucagon and glucose production and uptake. To determine whether infused oxytocin also increases glucagon secretion from extrapancreatic sites, pancreatectomized dogs, off insulin for 18 hr, were infused with oxytocin and plasma glucagon, and glucose production and uptake were measured using the [6-3H]glucose primer-infusion technique. The diabetic dogs, in the control period, had elevated plasma glucose and glucagon levels, an increased rate of glucose production, and a relative decrease in glucose uptake (decreased clearance).

Evidence that the [3H]estradiol-binding protein in pancreas is localized in exocrine cells.

Extracts of rat pancreas contain significant amounts of an [3H]estradiol-binding protein. The amount of steroid-binding activity that could be measured varied considerably depending on the tonicity of the homogenizing medium. High speed supernatants of homogenates initially prepared in isotonic buffer contained about 10% of the binding activity as homogenates prepared in hypotonic buffer.

Direct insertion and fluorescence studies of rhodamine-labeled beta-adrenergic receptors in cell membranes.

Previous studies utilizing the fluorescence of propanolol as a probe for the beta-adrenergic receptor showed that this receptor is motionally constrained. To further study the beta-adrenergic receptor in situ we have reinserted rhodamine-labeled beta-receptors into cell membranes. This report presents documentation of their insertion and physiologic viability.

Increased release of cyclic adenosine monophosphate into jugular vein in response to isoproterenol administration.

Catecholamine administration elevates plasma cyclic AMP (cAMP) levels but the source of the cAMP is unknown. To determine possible sources, plasma cAMP levels were determined in blood vessels across the head, liver, kidney and lung in anesthetized dogs infused with the beta-adrenergic agonist, isoproterenol. Only the head showed an increased release of cAMP into the blood.

Onset of changes in glucose transport across ocular barriers in streptozotocin-induced diabetes.

In a previous study, measurements were made of facilitated and passive transport of glucose, using [3H]-3-O-methyl-D-glucose and [14C]-L-glucose, respectively, across blood-aqueous and blood-vitreous barriers in long-term streptozotocin-diabetic rats. It was found that passive transport was increased, while facilitated transport was decreased, possibly due to saturation of the transport system. The present study examines the appearance of these changes in glucose transport at various times following streptozotocin (STZ) injection.

Tolbutamide and glyburide differ in effectiveness to displace alpha- and beta-adrenergic radioligands in pancreatic islet cells and membranes.

Previous in vivo findings indicated that alpha-adrenergic blocking agents enhanced tolbutamide-induced insulin secretion, whereas beta-blockade attenuated it. In the present study, the interaction of tolbutamide and glyburide with the rat islet adrenergic receptors is examined directly by determining the effectiveness of these drugs to displace the specific alpha- and beta-adrenergic radioligands, [3H]-clonidine and [3H]-dihydroalprenolol (DHA). It was found that both tolbutamide and glyburide had affinity constants for the adrenergic receptors that were similar to those for the natural receptor ligands and powerful antagonists.

Decreased insulin sensitivity and glucose tolerance in spontaneous canine hyperadrenocorticism.

Alterations in carbohydrate metabolism were evaluated in 60 dogs with untreated hyperadrenocorticism by measuring basal concentrations of plasma glucose and insulin and performing glucose and insulin tolerance tests. The 60 dogs could be divided into four groups based on paired glucose and insulin concentrations. Eight dogs had normal concentrations of both glucose and insulin.

Displacement of alpha- and beta-radioligands by specific adrenergic agonists in rat pancreatic islets.

Secretion of insulin is increased by beta-adrenergic agonists and inhibited by alpha-adrenergic agonists. However, administration of epinephrine, which acts on both types of receptors, inhibits insulin secretion. A preliminary study using [3H]-dihydroergocryptine and [3H]-dihydroalprenolol as the respective alpha- and beta-receptor binding ligands, surprisingly revealed a preponderance of beta-binding sites in normal rat pancreatic islets.

Glucose transport across ocular barriers of the streptozotocin-diabetic rat.

The transport kinetics across the plasma-aqueous and plasma-vitreous barriers were studied in normal and long-term streptozotocin-diabetic rats, using trace amounts of [14C]-L-glucose and [3H]-3-O-methyl-D-glucose. The former is passively transported while the latter uses the same transport-facilitating system as D-glucose. Transport rates of L-glucose were significantly higher in the diabetic rats, with ocular entry rates from the plasma being increased by 69% across both barriers.

Suppression of growth hormone secretion in spontaneous canine hyperadrenocorticism and its reversal after treatment.

The plasma growth hormone response to the provocative agent, xylazine, was assessed in 4 dogs with spontaneous hyperadrenocorticism, before and after therapy. Before treatment of the hyperadrenocorticism, no significant increase in growth hormone concentration occurred in any of the dogs following the administration of xylazine. A significant increase in growth hormone concentrations following xylazine administration occurred in 2 of the 3 dogs with hypophysis (pituitary)-dependent hyperadrenocorticism after treatment with mitotane (o,p'-DDD) and in 1 dog after surgical removal of a hyperfunctional adrenal adenoma.

Intranasal instillation of oxytocin increases insulin and glucagon secretion.

Intravenously administered oxytocin was found to increase plasma insulin and glucagon levels. To explore if the same effects could be obtained by nonparenteral routes of administration, oxytocin was given by nasal instillation in normal conscious dogs. Plasma glucose, insulin, and glucagon levels all increased to levels which previously were shown to cause increased glucose production and utilization.

Clonidine or xylazine as provocative tests for growth hormone secretion in the dog.

Base-line values of plasma growth hormone (GH) are low in most species, requiring provocative tests to assess GH deficiency. Clonidine, an antihypertensive drug, and its analogue, xylazine, a sedative hypnotic, were found to stimulate GH secretion. Administration (IV) of clonidine to conscious healthy, dogs at doses of 30, 16.

Oxytocin infusion increases plasma insulin and glucagon levels and glucose production and uptake in the normal dog.

Infusion of oxytocin (50--500 microU/kg/min) into normal conscious dogs produces a rise in plasma glucose, insulin, and glucagon levels. These changes are accompanied by a prompt increase in glucose production followed by an increase in overall glucose uptake, as determined using 6-3H-glucose infusion.