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E Samols

Publications and source records attributed to E Samols.

At least 37 records · Page 2Linked to original sources
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↗
PubMed1988

beta----alpha----delta pancreatic islet cellular perfusion in dogs.

Intraislet communication between alpha-, beta-, and delta-cells and their secretory products may theoretically occur via the paracrine (interstitial) and/or vascular routes. Recently, we have shown that there is a directed microvascular circulation in the rat islet with a cellular order of perfusion of beta----alpha----delta. The direction of microvascular perfusion of cells within the dog islet has been controversial. Anterograde (arterial) perfusion and retrograde (reversed or venous) perfusion of a segment of isolated dog pancreas with potent insulin antibodies yielded results similar to those found in the rat pancreas (anterograde, 158 +/- 44% increase in glucagon and 65 +/- 20% increase in somatostatin; retrograde, no change in glucagon or somatostatin). Anterograde infusion of glucagon antibody (no change in insulin, -33.5 +/- 3% decrease in somatostatin) or somatostatin antibody (no change in insulin or glucagon) also yielded the same results as in the rat pancreas. Anterograde infusion of 500 pg/ml glucagon caused a larger increase in insulin secretion (245 +/- 10%) than retrograde infusion (45 +/- 4%), whereas somatostatin was stimulated more retrogradely (339 +/- 17%) than anterogradely (121 +/- 9%). Anterograde infusion of somatostatin produced a larger decrease in insulin and glucagon than did retrograde perfusion (P less than .0001 for both comparisons). The retrograde infusion of 0.3 mU/ml insulin caused a decrease in glucagon but was without effect anterogradely. The results from the infusion of exogenous hormones suggest that the sensitivity of the alpha-, beta-, and delta-cells to insulin, glucagon, and somatostatin is determined by the beta----alpha----delta order of perfusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Development of a method to determine autonomic nervous system function in the rat.

A noninvasive method to evaluate autonomic nervous system (ANS) function in animals is needed for studies of diabetic autonomic neuropathy. These studies modified the RR-variation test, used to test diabetic ANS function in humans, and applied it to rats. Permanent wire electrodes were implanted in the chest wall of a rat. ECG complexes were obtained by connecting the electrodes to leads going to an impedence pneumograph and high gain coupler. This information was then converted into square waves by a trigger unit and recorded on magnetic tape for subsequent analysis by computer. Recordings were at least 60 seconds long, of which 30 seconds was used for analysis. In order to establish autonomic influence, RR-variation was measured before and after application of pharmacologic agents. Directly decreasing parasympathetic tone with atropine (20 mg/kg, n = 6) increased heart rate (P less than 0.001) and decreased RR-variation (P less than 0.05). Directly decreasing beta adrenergic tone with propranolol (10 mg/kg, n = 7) decreased heart rate (P less than 0.01) but had no effect on RR-variation (NS). Stimulation of the beta adrenergic receptors (isoproterenol, 0.1 mg/kg, n = 5) increased heart rate (P less than 0.01) but decreased RR-variation (P less than 0.01). Increasing parasympathetic tone reflexly with alpha-1 adrenergic receptor stimulation (phenylephrine, 1 mg/kg, n = 7) decreased heart rate (P less than 0.05) and increased RR-variation (P less than 0.025). The responses to phenylephrine could be blocked by parasympathetic blockade. Phentolamine (0.1 mg/kg, n = 7) caused an increase in heart rate (P less than 0.001) and a decrease in RR-variation (P less than 0.01). The responses to phentolamine could be blocked by beta adrenergic receptor blockade.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-Antagonists↗
PubMed1987

Alpha-adrenergic blockade improves glucose-potentiated insulin secretion in non-insulin-dependent diabetes mellitus.

The impairment of glucose-potentiated insulin secretion present in non-insulin-dependent diabetes mellitus (NIDDM) can be approximated in normal subjects by an epinephrine infusion. Therefore, we sought to determine the role of the endogenous sympathetic nervous system in glucose-potentiated insulin secretion in both NIDDM (n = 6) and normal (n = 6) subjects. Glucose-potentiated insulin secretion was calculated as the slope of the curve relating increasing ambient glucose levels to the acute insulin response to an intravenous pulse of 5 g of L-arginine. Glucose-potentiated insulin secretion was determined on separate days during alpha-, beta-, and combined alpha- plus beta-adrenergic blockade and compared with a saline control. In normal subjects, there was no effect of alpha-, beta-, or alpha- plus beta-blockade on the slope of glucose potentiation. In NIDDM, the initially decreased slope of glucose potentiation (0.25 +/- 0.06 microU X ml-1 X mg-1 X dl, mean +/- SE; P less than .01) was not affected by beta-blockade but increased during alpha-blockade (0.91 +/- 0.22 microU X ml-1 X mg-1 X dl; P less than .05). However, this improvement was abolished by combined alpha- plus beta-blockade (0.32 +/- 0.07 microU X ml-1 X mg-1 X dl). Plasma norepinephrine was increased above basal levels in both normal (+260 +/- 89 pg/ml) and NIDDM (+438 +/- 162 pg/ml) subjects during alpha-blockade (P less than .05 for both). This increase in plasma norepinephrine strongly suggests that there is an increase in synaptic cleft norepinephrine concentration.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-Antagonists↗
PubMed1986

Retrograde perfusion as a model for testing the relative effects of glucose versus insulin on the A cell.

In order to determine whether the A cell may be directly suppressed by glucose in the absence of insulin, canine pancreata were perfused in vitro, both antegrade, through the arterial system and retrograde, through the venous system. Studies of the islet microvasculature have suggested that blood flows from the B cell core to the mantle; thus, the A cell may be tonically inhibited by intra-islet insulin. Retrograde perfusion may then be expected to prevent insulin from reaching the A cell, releasing it from inhibition. Retrograde perfusion with 88 mg/dl glucose markedly increased both insulin and glucagon secretion relative to antegrade levels. In a series of experiments, glucose concentrations were changed from 88 to 200 mg/dl. An antegrade glucose change resulted in increased insulin (134+/-21%; P less than 0.0025) and decreased glucagon (-26+/-9%, P less than 0.025) secretion. A retrograde glucose increase resulted in increased secretion of both insulin (91+/-15%; P less than 0.0005) and glucagon (23+/-9%; P less than 0.0125). To confirm that retrograde perfusion deprived the A cell of endogenous core derived, vascularly delivered insulin, possibly resulting in increased insulin sensitivity, 0.3 mU/ml exogenous porcine insulin was infused. Antegrade, 0.3 mU/ml insulin, had no effect on glucagon secretion (P less than 0.250), while retrograde infusion of 0.3 mU/ml insulin significantly inhibited glucagon secretion (-31 + 8%; P less than 0.0005). The results of our study support the concept that the direction of blood flow and of flow-dependent intra-islet hormone interactions are from the islet B cell core to the mantle. It was further concluded that the normal A cell may not be suppressed by glucose in the absence of insulin.

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↗
PubMed1986

Modulation of insulin secretion by pancreatic ganglionic nicotinic receptors.

Autonomic ganglia may be regulated, in part, by nicotinic receptors. To test whether basal insulin secretion may be modulated by an endogenous pancreatic ganglionic mechanism, the effects of ganglionic pre- and postsynaptic nicotinic receptor antagonism were studied in the in vitro canine pancreas. Combined infusion of atropine, phentolamine, and propranolol had no affect on insulin secretion (P less than .30). Presynaptic nicotinic receptor blockade by beta-bungarotoxin (beta-BuTX) in combination with atropine and phentolamine reduced mean insulin secretion (78 +/- 18 U/ml, P less than .0025) from preinfusion concentrations (287 +/- 43 U/ml). The decrease in insulin secretion resulting from BuTX, atropine, and phentolamine was prevented by the addition of either specific postsynaptic nicotinic receptor blockade by alpha-bungarotoxin (P less than .05) or propranolol (P less than .005). Because it is known that postsynaptic nicotinic receptor agonism may stimulate the intraganglionic release of norepinephrine, these results suggest that nicotinic receptors are present at the ganglionic level in the pancreas and modulate insulin secretion by a complex intraganglionic mechanism. The postulated ganglionic nicotinic receptor-mediated mechanism may operate by the interaction of a beta-adrenergic inhibitory component, which may be activated by intraganglionic norepinephrine, and a stimulatory nonmuscarinic nonadrenergic (possibly peptidergic) component, which may be activated in the absence of intraganglionic norepinephrine.

Animals↗
PubMed1985

Perturbation of insulin oscillations by nerve blockade in the in vitro canine pancreas.

The in vitro canine pancreas produces an oscillatory pattern of insulin secretion during a constant glucose concentration despite the lack of external nervous modulation or recirculating hormone feedback. The normal period of insulin fluctuations (7.4 +/- 0.34 min) is unaffected by combined adrenergic and cholinergic blockade by 5 microM atropine, 4 microM propranolol, and 4 microM phentolamine (8.0 +/- 0.31 min, P less than 0.20). To test the theory that the coordination of islet secretion may be controlled by an intrapancreatic nervous system (nonadrenergic, noncholinergic), nerve blockade was attempted by the infusion of tetrodotoxin (TTX) on a background of combined autonomic blockade. TTX infusion resulted in a change in the oscillatory pattern of insulin release by increasing net insulin release and shifting the period of oscillation to 4.5 +/- 0.29 min (P less than 0.0005) at both 88 and 200 mg/dl glucose. These results suggest that an intrinsic autonomously functioning pancreatic nervous system is responsible for the coordination of islet secretion and the production of periodic fluctuations of insulin secretion.

Animals↗