PubMed Health⌕ Search

Biomedical subjects

E Samols

Publications and source records attributed to E Samols.

At least 19 recordsLinked to original sources
PubMed1995

In situ binding of islet hormones in the isolated perfused rat pancreas: evidence for local high concentrations of islet hormones via the islet-acinar axis.

Insulin and somatostatin reportedly affect pancreatic acinar cell function via specific receptor binding. Theoretically peri-insular levels depend on the islet-acinar portal system, but the actual hormone levels have never been demonstrated. Rat pancreata were perfused anterogradely or retrogradely with 125I-insulin, -somatostatin, or -glucagon (each, approximately equal to 10(-11) mol/l). Tracer binding was determined from differences between influx and efflux radioactivity. Saturable binding was observed for insulin and somatostatin, but not for glucagon. Binding in the absence of unlabelled peptides was significantly higher during retrograde perfusion than during anterograde perfusion for insulin (25.9 +/- 2.6 vs 16.0 +/- 2.1%, mean +/- SD; each, n = 4; p < 0.001) and somatostatin (18.4 +/- 2.0 vs 13.6 +/- 1.2%; each, n = 3; p < 0.05). Non-specific binding was similar in both directions. These findings are attributable to endogenous hormones acting as unlabelled ligands competing with the tracers during anterograde perfusion. This conclusion was supported by the demonstration that endogenous insulin stimulation by D-glucose, but not by L-glucose, caused a decrease in labelled insulin binding only during anterograde perfusion. Displacement curves obtained during retrograde perfusion showed that interstitial concentrations of insulin and somatostatin were 7.5 x 10(-9) and 1.1 x 10(-9) mol/l, respectively. Thus, the exocrine pancreas is indeed exposed to locally high concentrations of islet hormones.

Animals↗
PubMed1993

Suppressive role of the islet-acinar axis in the perfused rat pancreas.

BACKGROUND: The stimulating effects of insulin on the exocrine pancreas are well known. The effects of other islet hormones, however, are controversial. The aim of the present study was to determine whether the islet-acinar axis, as a whole, is stimulatory or inhibitory. Because we have shown that retrograde perfusion reverses the islet-acinar directed microcirculation, retrograde perfusion was expected to remove the overall effects of islet hormones from the acinar tissue. METHODS: Rat pancreata were perfused (7 mmol/L glucose plus 3 mmol/L mixed amino acids) either anterogradely or retrogradely. Pancreatic juice flow, protein output, and amylase output were measured. RESULTS: When perfusion was switched from anterograde to retrograde, juice flow increased threefold without changes in protein and amylase output. When cerulein (10(-10) mol/L) was infused, retrograde protein and amylase responses were larger than anterograde responses (each, n = 7; 2.71 +/- 0.23 vs. 1.71 +/- 0.11 mg/40 minutes; 173 +/- 17 vs. 98 +/- 8 U/40 minutes; mean +/- SE; both, P < 0.01). Somatostatin-14 and rat pancreatic polypeptide (each, 10(-9) mol/L) reduced the retrograde protein and amylase responses, but not juice flow, to the anterograde response levels. Conversely, these peptides did not affect exocrine function during anterograde perfusion. CONCLUSIONS: A suppressive role of the islet-acinar axis via endogenous somatostatin and/or pancreatic polypeptide is suggested.

Amino Acids↗
PubMed1992

Induction of angiogenesis by growth factors: relevance to pancreatic islet transplantation.

Biodegradable pellets releasing 20 ng/day of endothelial cell growth factor alpha (alpha ECGF) or a- or b-fibroblast growth factor (FGF) and 90 micrograms/day of heparin were implanted beneath the renal capsule in rats and dogs and the muscularis/serosal border of the pyloric stomach in dogs to test for angiogenesis in a potential pancreatic islet transplant site. These factors were also tested in vitro to determine whether the capillary bed of the isolated islet could be preserved. alpha ECGF was superior to a- or bFGF in promoting endothelial cell growth and capillary formation in isolated islets. Both a- or bFGF and alpha ECGF induced the development of a dense capillary bed in the dog stomach, whereas in the kidney site alpha ECGF was more effective in the rat than was a- or bFGF. Priming the isolated islet as well as the transplant site prior to islet transplantation resulted in islet blood flow being established within 3 days in contrast to 7-14 days in controls.

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

Perfusion with anti-insulin gamma globulin indicates a B to A to D cellular perfusion sequence in the pancreas of the rhesus monkey, Macaca mulatta.

The cellular sequence of intraislet vascular perfusion has been shown to be important in the regulation of islet hormone secretion in the rat and dog islet. In order to test whether a B to A to D sequence of islet cellular perfusion is also present in a nonhuman primate, pancreata from the rhesus monkey, Macaca mulatta, were isolated and perfused in vitro in the presence and absence of anti-insulin gamma globulin. In the presence of the insulin antibody, efflux concentration of insulin decreased rapidly (-95 +/- 1.8%), whereas glucagon and somatostatin concentrations increased (111 +/- 28% and 239 +/- 38%, respectively). These results suggest the presence of a B-A-D cellular sequence of vascular perfusion within the monkey islet. The present results also strongly support the hypothesis that a B-A-D sequence of islet perfusion is important in the regulation of islet hormone secretion and further emphasize the central role of the B-cell in intraislet cellular interactions. The results also suggest that, despite differences in islet anatomy, a B-A-D order of islet cellular perfusion may be the preferred functional sequence among mammalian species.

Animals↗
PubMed1992

Body fat distribution and peripheral insulin sensitivity in healthy men: role of insulin pulsatility.

Abdominal fat distribution is associated with insulin resistance in healthy young men. Factors modulating this phenomenon remain unclear. Pulsatile insulin release has been implicated as a potential regulator of insulin action. The relationship of pulsatility of peripheral insulin levels to fat distribution and peripheral insulin sensitivity was examined in 10 healthy men. Fat distribution was determined by the waist to hip ratio. Peripheral insulin sensitivity was assessed by the euglycemic clamp at an insulin infusion rate of 287 pmol/min.m2. Pulsatility of insulin was assessed by sampling every 2 min for 90 min in the basal state. The characteristics of insulin pulses were assessed by the computer program Pulsar. The waist to hip ratio was negatively associated with insulin sensitivity (r = -0.70, P less than 0.05) and insulin pulse interval (r = -0.66, P less than 0.05). The insulin pulse interval was positively correlated with peripheral insulin sensitivity (r = 0.73, P less than 0.05). The insulin interpulse interval was the primary determinant of insulin sensitivity. The increased frequency of insulin pulses may play a role in inducing insulin resistance in individuals with abdominal fat distribution.

Abdomen↗
PubMed1992

The vascular order of islet cellular perfusion in the human pancreas.

The vascular order of pancreatic islet cellular perfusion is important in the intraislet regulation of hormone secretion. Establishment of the sequence of interaction is fundamental to understanding the physiology and pathophysiology of the human islet. Intraislet insulin from the beta-cell regulates both net hormone secretion and pulsatile secretion from alpha- and delta-cells. In terms of vascular perfusion, the delta-cell is perfused last and does not directly affect alpha- or beta-cells in humans.

Adult↗
PubMed1991

In vitro pancreatic hormonal pulses are less regular and more frequent than in vivo.

Spontaneous in vivo cyclic secretion of insulin and glucagon displays a pulse interval of 10 +/- 0.3 (SE) min and a constant phase relationship in fasting rhesus monkeys. When pancreata from six normal rhesus monkeys were perfused in vitro, the insulin pulse interval averaged 6.3 +/- 0.23 (SE) min. Insulin, glucagon, and somatostatin displayed high-amplitude secretory pulses, and the average pulse interval did not differ among the three islet hormones. The islet pulses are less regular in vitro than in vivo, and the phase relationship among the three hormones is lost. The relative amplitude averaged 142 +/- 10, 110 +/- 18, and 81 +/- 11% of the mean hormone concentrations for insulin, somatostatin, and glucagon, respectively. Similar differences in secretory pattern were observed during perfusion of three baboon pancreata compared with the in vivo pattern in this second primate species. The data suggest that the frequency and phase relationship of the islet pulsatile secretory system is modulated by factors extrinsic to the pancreas in the intact nonhuman primate. The nature of these modulating factors remains to be established. The apparent phase independence of the three islet hormones suggests that each of the major endocrine cell types of the islet possess independent episodic secretory mechanisms.

Animals↗
PubMed1991

Deterioration of islet beta-cell function after hemipancreatectomy in dogs.

The metabolic consequences of hemipancreatectomy in living pancreas donors were tested in a dog model in which a 50% lobe-specific pancreatectomy was performed. Removal of the dorsal lobe (analogous to a donor, n = 4) resulted in a progressive increase in fasting glucose during 12 mo from 5.32 +/- 0.16 to 8.17 +/- 0.28 mM and a decrease in fasting insulin from 54 +/- 3 to 6.0 +/- 2.4 pM and glucose clearance (Kg) from 3.00 +/- 0.22 to 1.00 +/- 0.06 mM. Removal of the ventral lobe (analogous to a recipient, n = 5) did not result in a change in fasting glucose or Kg during 12 mo, although fasting insulin was reduced from 36.0 +/- 1.8 to 18.00 +/- 1.93 pM. In vitro perfusion of the remnants after 1 yr showed a deterioration in glucose-stimulated insulin secretion (5-11 mM) by the dorsal remnant (18 +/- 11 vs., 232 +/- 37%) and the ventral remnant (2.6 +/- 19 vs. 87 +/- 13%). The dorsal remnant had a higher response than the ventral remnant (46 +/- 23 vs. -16 +/- 10%, respectively) to severe hyperglucosuria (11-27.7 mM). Insulin content was unchanged in the dorsal remnant (224 +/- 16 vs. 180 +/- 14 micrograms/g), but was reduced in the ventral remnant (65 +/- 14 vs. 154 +/- 15 micrograms/g). In vitro insulin pulse intervals were reduced in both remnants (5.3 +/- 0.2 min vs. control 7.00 +/- 0.18 min). Because of the above effects on the donor when the dorsal lobe is removed, the continued use of hemipancreatectomy as a source of transplantable tissue must be questioned.

Animals↗
PubMed1990

Islet somatostatin--microvascular, paracrine, and pulsatile regulation.

The possible role of the D cell in the regulation of islet hormone secretion has been controversial for many years. It is known that the D cells characteristically reside in the islet mantle interspaced among A cells. We have shown by the anterograde and retrograde infusion of antibody directed against insulin, glucagon, or somatostatin into the isolated rat and dog pancreas that blood flow within the islet is from the B-cell core outward to the mantle. Despite the apparent randomness of the A and D cell in the mantle, our results indicate a further suborder of cellular perfusion in the mantle with the A cells perfused before the D cells. The D cells are last in line in terms of secretion. Thus the D cell is vascularly neutral and cannot directly effect A- or B-cell secretion through the intra-islet vasculature. Our results demonstrate that the B to A to D cellular order of perfusion is responsible for the regulation of islet hormone secretion, ie, insulin regulates the secretion of glucagon and glucagon (and probably insulin) regulate the secretion of somatostatin. Although each hormone is secreted as pulses, there does not appear to be a consistent phase relationship between insulin, glucagon, or somatostatin. The B to A to D cellular order of perfusion is responsible for net and integrated hormone secretion, but may not be the motive force of pulsatile secretion. Our studies have not documented a role for intra-islet mantle somatostatin. These results strongly suggest that the D cell is not a paracrine regulator of islet hormone secretion, but may be important in the regulation of exocrine function.

Animals↗
PubMed1989

The anterograde and retrograde infusion of glucagon antibodies suggests that A cells are vascularly perfused before D cells within the rat islet.

We have suggested that the order of cellular vascular perfusion within the islet is important in the regulation of islet hormone secretion. Anatomically, the A and D cells appear to be randomly dispersed throughout the mantle. Although islet capillary blood flow is known to be from the B-cell core to the A- and D-cell mantle, it has not yet been established whether the cells of the mantle may influence one another vascularly. Rat pancreata were perfused in vitro anterogradely and retrogradely with or without glucagon antibody in order to determine the order of cellular perfusion and interaction between the A and D cells in the islet mantle. Anterograde infusion of glucagon antibody did not affect insulin secretion, but rapidly decreased somatostatin secretion -46 +/- 8%, (p less than 0.005). Retrograde infusion of glucagon antibody decreased insulin secretion (-27 +/- 8%, p less than 0.005) but had no effect upon somatostatin secretion. This study not only confirms a core to mantle islet perfusion but also establishes that the A cell precedes the D cell in the terms of vascular perfusion. Thus within the islet, vascular borne insulin regulates the release of glucagon, which in turn, regulates the release of somatostatin. Somatostatin is vascularly neutral owing to its downstream position in the sequence (B to A to D) of cellular perfusion.

Animals↗
PubMed1989

Autonomic influence on cardiovascular performance in diabetic subjects.

PURPOSE: Cardiomyopathy, coronary artery atherosclerosis, or autonomic neuropathy may affect the cardiovascular performance of the diabetic patient. To evaluate the role of parasympathetic nervous system activity on cardiovascular performance, 25 diabetic subjects who lacked symptoms, signs, or objective measurements of ischemia or cardiomyopathy were studied. PATIENTS AND METHODS: Diabetic subjects were classified according to their RR variation, an index of cardiac parasympathetic nervous system activity. Fourteen diabetic subjects had a normal RR variation of greater than 30 (D-NOR), and 11 diabetic patients had an abnormal RR variation of less than 20 (D-ABN). Fifteen age- and weight-matched, healthy, nondiabetic subjects (NOR) constituted the control group. All subjects had oxygen consumption, multigated acquisition determination of cardiac output, and work product measured before and during supine bicycle maximum exercise testing. RESULTS: There was no difference in the resting cardiac output among the groups. Resting work product, however, was greatest in the D-ABN group when compared with performance in the other two groups (D-ABN: 11,500 +/- 800; D-NOR: 9,000 +/- 600; NOR: 8,700 +/- 400; p less than 0.0025). This was due to an increase in both heart rate (p less than 0.025) and systolic blood pressure (p less than 0.015). In the diabetic subjects, there was an inverse relationship between the RR variation and resting work product (r = 0.47, n = 25, p less than 0.005). In response to exercise, the percent increase in cardiac output at matched percent maximum oxygen uptake was greatest in the NOR, D-NOR, and D-ABN groups, respectively (analysis of variance, p less than 0.01). In the diabetic subjects, there was a significant relationship between the RR variation and the maximum percent change in cardiac output (r = 0.41, n = 25, p less than 0.02). Compared with the NOR group, the maximum increase in work product was impaired in diabetic subjects (p less than 0.002) and not different between the D-NOR and D-ABN groups. CONCLUSIONS: The increase in resting work product and the poor cardiac output responses to exercise in the D-ABN group are due to a decrease in cardiac parasympathetic nervous system activity and can be suggested by an abnormal RR variation. This index of parasympathetic nervous system activity can help the physician identify that subset of diabetic patients that may need special consideration when exercise training is prescribed.

Adult↗
PubMed1988

Intra-islet regulation.

Intra-islet regulation of islet cells by one another is theoretically possible by two routes: (1) paracrine (i.e., interstitial, which is unproved); and (2) direct cellular perfusion through the islet microvasculature. The latter was tested in in vitro rat pancreases by anterograde and retrograde perfusion with or without anti-insulin or antisomatostatin antibody. Anterograde infusion of insulin antibody increased glucagon and somatostatin secretion (p less than 0.0005), whereas retrograde insulin antibody infusion was without effect. Anterograde infusion of somatostatin antibody had no effect upon insulin or glucagon secretion. In contrast, retrograde infusion of somatostatin antibody increased both insulin and glucagon secretion (p less than 0.0005). In comparison, anterograde infusion of antiglucagon antibody decreased somatostatin secretion without influencing insulin, whereas retrograde antiglucagon antibody infusion decreased insulin without changing somatostatin secretion. These results establish a "directed" functional microvascular circulation with a strict sequence of perfusion, first of B cells, then A cells, then D cells. The B cell microvascularly is the primary glucose sensor and its insulin plays a vital role in inhibiting glucagon secretion. The abnormalities in glucagon secretion in diabetes mellitus can now be explained by a deficiency in intra-islet microvascular insulin.

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↗
PubMed1988

The order of islet microvascular cellular perfusion is B----A----D in the perfused rat pancreas.

In order to determine whether microvascular blood flow is important in the regulation of intra-islet cellular interactions, rat pancreata were isolated and perfused in vitro, both anterogradely or retrogradely, with and without anti-insulin or anti-somatostatin gamma-globulin. Expressed as percent change, anterograde infusion of insulin antibody increased efflux concentrations of glucagon (110 +/- 20%, P less than 0.0005) and somatostatin (2,112 +/- 73%, P less than 0.0005) above their respective control. Retrograde infusion of insulin antibody did not affect efflux concentrations of glucagon (P less than 0.50) or somatostatin (P less than 0.50). The anterograde infusion of anti-somatostatin antibody had no effect upon insulin (P less than 0.50) or glucagon (P less than 0.50) efflux concentrations, whereas retrograde anti-somatostatin antibody infusion produced immediate increases in efflux concentrations of both insulin (115 +/- 33%, P less than 0.0005) and glucagon (77 +/- 8%, P less than 0.0005). These results strongly suggest that (a) the vascular compartment is important in the regulation of intra-islet cellular interactions and further suggest that (b) the order of islet cellular perfusion and interaction is from the B cell core outward to the mantle, and (c) the mantle is further subordered with the majority of D cells downstream or distal to the majority of A cells. Thus, in the vascular compartment, B cells inhibit A-cell secretion and A cells stimulate D-cell secretion.

Animals↗