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J Stagner

Publications and source records attributed to J Stagner.

7 recordsLinked to original sources
PubMed2004

Beta-cell sparing in transplanted islets by vascular endothelial growth factor.

We have reported that vascular endothelial growth factor (VEGF) promotes the revascularization of transplanted islets, thereby reducing the initial number required to prevent diabetes. The present study was undertaken to assess other mechanisms of beta-cell sparing by VEGF. For in vitro studies, islets were cultured for 14 days with versus without 20 ng/mL VEGF. Viability, necrosis, and apoptosis were examined by specific staining (Alcein AM, propidium iodide, and annexin/phosphatidylserine). The effects of VEGF on islets were also examined in a proteomic study. In vivo streptozotocin-treated diabetic Lewis rats received 1000 Lewis or Sprague-Dawley islets beneath the renal capsule. Oxygen levels at the transplant site were monitored by a Clark-type oxygen electrode. Fasting blood glucose served as an indicator of islet survival and function. VEGF enhanced oxygen levels at the transplant site. Syngeneic recipients were euglycemic for over 6 months, whereas control islets failed within 30 to 60 days. VEGF prevented allograft rejection for over 14 days, whereas controls were rejected within 6 to 7 days. Immunostaining suggested that VEGF inhibited the presentation of MHC II antigen and promoted islet survival by the inhibition of necrosis and apoptosis. Our proteomic study suggested VEGF preserved systems required for cellular preservation (heat shock proteins) and insulin secretion. VEGF promotes the preservation of isolated and transplanted islets by a variety of mechanisms, including enhanced oxygenation and inhibition of immune rejection, necrosis, and apoptosis. The provision of exogenous VEGF may be a useful adjunct to islet transplantation.

Animals↗
PubMed1992

Islet hormone pulse intervals are dependent upon sampling frequency.

Pulsatile insulin secretion has been reported from a variety of in vivo and in vitro systems. While it is agreed that insulin pulses exist, there is little agreement concerning the basal frequency or interpulse interval either within the same species in vivo, as both long and short term pulses have been reported, or between in vivo and in vitro preparations. We propose that the frequency of sampling may have profound effects upon the calculated pulse interval. Three systems were used to test this hypothesis: 1) artificial test data were designed to produce regular pulses with an exact 11 min period, 2) perfusate insulin concentration from isolated canine pancreata sampled at 1 min intervals and 3) peripheral blood insulin concentrations from human volunteers sampled every 2 and 5 min. Pulse parameters were determined at 1, 2, 5, 20, 15, 30 and 60 min sampling intervals for each data set by the use of the computer algorithms Pulsar and Cycle Detector. The results indicate that for insulin secretory pulses, sampling frequencies longer than 2 min may result in the production of spurious pulse trains with multiple longer term pulse periods. It is concluded that islet hormone secretory pulse period calculations are dependent upon the sampling frequency.

Analysis of Variance↗
PubMed1992

Endothelin does not affect experimentally induced corneal neovascularization.

Endothelin, a potent vasoconstrictor, was found to be ineffective in the treatment of experimentally induced corneal neovascularization. Endothelin was administered topically, subconjunctivally, and intraluminally in serial concentrations ranging from 0.0005 to 5.0 micrograms/mL in New Zealand white rabbits without effect. Electron microscopy of the neovascular cornea revealed the vessels consisted only of endothelin and pericytes. Hence, the vessels were not responsive to endothelin because they lacked contractile smooth muscle.

Animals↗
PubMed1988

Comparison of insulin and glucagon pulsatile secretion between the rat and dog pancreas in-vitro.

Sustained pulses of insulin and glucagon were obtained from the isolated perfused in vitro rat pancreas. The respective periodicity of hormone release (peak to peak interval) was calculated by the Pulsar computer algorithm as insulin 5.8 +/- 0.3 min and glucagon 6.5 +/- 0.25 min. Because pulsatile insulin secretion is absent in type II diabetics, pulsatile islet hormone secretion could theoretically be regulated directly by intra-islet hormone interactions or indirectly by hormone sensitive nerve feedback, possibly from a venous hormone sensitive receptor system within the pancreas. To test the possible contributions of these systems in pulse regulation, the direction of perfusion was reversed in both rat and dog pancreata to prevent hormone contact with putative venous hormone receptors. The periodicity of hormone secretion was unchanged by reversed perfusion in both species. As vascular perfusion of islet cells is normally B to A to D, these results suggest that neither intra-islet hormone interactions nor intra-pancreatic insulin or glucagon sensitive nerve feedback systems are responsible, on an acute basis, for the regulation of pulsatile insular secretion from the normal pancreas. Insulin regulates net glucagon secretion but does not acutely influence glucagon pulses. The presence of pulses during retrograde perfusion may be the result of the entrainment of the pacemaker-islet system. These observations are consistent with the presence of an independent pacemaker and neural coordinating system within the dog and rat pancreas which may influence both the A- and B-cell.

Animals↗
PubMed1986

Lack of direct inhibition of insulin secretion by exogenous insulin in the canine pancreas.

To test whether insulin secretion is self-regulatory, canine pancreata were isolated and perfused in vitro and were infused with 0.3, 0.6, or 1.2 mU/ml exogenous insulin. Basal and arginine-stimulated concentrations of C-peptide, glucagon, and somatostatin were measured. There were no significant differences between basal secretion nor the increment of arginine-stimulated secretion for each respective hormone at each exogenous insulin concentration. The second preparation studied was a vascularly isolated, yet innervated, in situ perfused pancreas. Exogenous insulin (1 mU/kg per min) was infused "systemically"; the pancreas received no insulin. Endogenous pancreatic insulin and C-peptide secretion was suppressed, while pancreatic glucagon secretion increased during systemic insulin infusion. No changes in pancreatic hormone secretion occurred after the sympathetic nerves were sectioned. These results suggest that exogenous insulin does not directly suppress the B cell, but can suppress insulin secretion through an indirect neurally mediated, insulin-dependent nerve mechanism.

Animals↗
PubMed1982

Abolition of dopaminergic insulin secretion by beta-adrenergic antagonism.

To determine whether the insulinotropic effects of dopamine were mediated through the adrenergic system, dogs were infused with dopamine before or after various combinations of adrenergic and cholinergic blockade. Plasma glucose levels did not change significantly throughout the individual experiments, although cardiovascular effects from both blockade and dopamine infusion were demonstrated. The pronounced in vivo insulinotropic effects of dopamine were abolished by beta-adrenergic blockade with propranolol and all subsequent combinations of propranolol, phentolamine, and atropine. These results contrast with the in vitro suppression of insulin by dopamine, which is abolished by alpha-adrenergic blockade by phentolamine. Therefore, it may be concluded that the prevention of dopamine effects on insulin secretion by adrenergic antagonism is evidence that dopamine exerts its effects on the B cell directly or indirectly through the adrenergic system.

Adrenergic beta-Antagonists↗