Stimulation of insulin secretion reveals heterogeneity of pancreatic B cells in vivo.

The development of gap junctions between pancreatic B-cells was quantitatively assessed in freeze-fracture replicas of isolated rat islets under different conditions of insulin secretion. The results show that in resting B-cells, gap junctions are small and scarce but that these junctions increase when insulin secretion is stimulated. Both a short (90 min) stimulation by glucose in vitro and a prolonged (2.5 d) stimulation by glibenclamide in vivo raise the number of gap junctions; in addition, the glibenclamide stimulation causes an increase in the size of individual gap junctions. As a consequence, the total area occupied by gap junctions on the B-cell membrane and the ratio of this area to the cell volume were found significantly increased in the latter condition. The slight increase of these values observed after the glucose stimulation did not reach significance. These data indicate a change of gap junctions during the secretory activity of the pancreatic B-cells. The possibility that the coupling of the cells is affected by the treatment is discussed.

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Hyperinsulinemia of preobese and obese fa/fa rats is partly vagus nerve mediated

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1983.244.4.e317 ◽

1983 ◽

Vol 244 (4) ◽

pp. E317-E322 ◽

Cited By ~ 7

Author(s):

F. Rohner-Jeanrenaud ◽

A. C. Hochstrasser ◽

B. Jeanrenaud

Keyword(s):

Electrical Stimulation ◽

Insulin Secretion ◽

B Cells ◽

Vagus Nerve ◽

Zucker Rats ◽

Glucose Load ◽

Parasympathetic System ◽

Enhanced Sensitivity ◽

Stimulation Of

In vivo glucose-induced insulin secretion was greater in preweaned preobese 17-day-old Zucker rats than in the corresponding controls. This hypersecretion of insulin was reversed to normal by acute pretreatment with atropine. A short-lived (30 s) electrical stimulation of the vagus nerve preceding a glucose load potentiated the in vivo glucose-induced insulin release in adult animals (6-9 wk) and more so in obese Zucker (fa/fa) than in lean rats. This suggested the existence of enhanced sensitivity and/or responsiveness of the B cells of obese animals to the parasympathetic system. That the parasympathetic tone was increased in adult obese Zucker (fa/fa) rats was corroborated by the observation that acute vagotomy of these animals resulted in a significant decrease in glucose-induced insulin secretion, whereas no such effect was seen in lean rats. Also, perfused pancreases from adult obese (fa/fa) rats oversecreted insulin during a stimulation by arginine when compared with controls, an oversecretion that was restored toward normal by superimposed infusion of atropine. It is concluded that a) the increased insulin secretion of preobese Zucker fa/fa rats is an early abnormality that is mediated by the vagus nerve, and b) increased secretion of insulin in adult obese fa/fa rats continues to be partly vagus-nerve mediated, although a decreased sympathetic tone and other unknown defects could conceivably play a role as well.

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RELATION BETWEEN ALLOXAN-INDUCED PLASMA MEMBRANE DYSFUNCTION AND INHIBITION OF INSULIN SECRETION IN PANCREATIC B-CELLS IN VIVO

Acta Pathologica Microbiologica Scandinavica Series A Pathology ◽

10.1111/j.1699-0463.1986.tb02978.x ◽

2009 ◽

Vol 94A (1-6) ◽

pp. 153-158

Author(s):

EVA Jennische ◽

HANS-ARNE Hansson

Keyword(s):

Plasma Membrane ◽

Insulin Secretion ◽

B Cells ◽

Pancreatic B Cells

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GPR40 Is Necessary but Not Sufficient for Fatty Acid Stimulation of Insulin Secretion In Vivo

Diabetes ◽

10.2337/db06-1532 ◽

2007 ◽

Vol 56 (4) ◽

pp. 1087-1094 ◽

Cited By ~ 196

Author(s):

M. G. Latour ◽

T. Alquier ◽

E. Oseid ◽

C. Tremblay ◽

T. L. Jetton ◽

...

Keyword(s):

Insulin Secretion ◽

Fatty Acid ◽

Insulin Secretion In Vivo ◽

Stimulation Of

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Interactions between cholinergic agonists and enteric factors in the regulation of insulin secretion from isolated perifused rat islets

Acta Endocrinologica ◽

10.1530/acta.0.1200702 ◽

1989 ◽

Vol 120 (6) ◽

pp. 702-707 ◽

Cited By ~ 15

Author(s):

Walter S. Zawalich ◽

Kathleen C. Zawalich ◽

Howard Rasmussen

Keyword(s):

Insulin Secretion ◽

Gastric Inhibitory Polypeptide ◽

Moderate Increase ◽

Rat Islets ◽

Insulin Requirements ◽

Isolated Rat Islets ◽

First Phase Insulin Secretion ◽

Sensitizing Effect ◽

Stimulation Of

Abstract. The ability of the cholinergic agonist carbachol to sensitize islets to the action of combined glucose, cholecystokinin and gastric inhibitory polypeptide was determined in isolated rat islets. In response to this combination, peak first phase insulin secretion from control islets averages 85 ± 5 pg · islet−1 · min−1 (mean ± sem) and the insulin secretory rates measured 35–40 min after the onset of stimulation averages 127 ± 34 pg · islet−1 · min−1. A prior 20 min exposure to 1 mmol/l carbachol potentiates the modest insulin stimulatory response to this combination of stimulants: peak first phase release is 354 ± 61 pg · islet−1 · min−1, and release measured 35–40 min after the onset of stimulation is 179 ± 34 pg · islet−1 · min−1. This sensitizing effect of carbachol lasts for at least 40 min and can be duplicated by the natural in vivo agonist acetylcholine. These results demonstrate that cholinergic stimulation of isolated islets primes them to the subsequent stimulatory effect of a moderate increase in the circulating glucose level and to several postulated incretin factors. If operative in vivo, this communications network between cephalic and enteric factors represents a remarkable control system to ensure the release of insulin in amounts commensurate to meet the anticipated and actual insulin requirements for insulin-mediated fuel disposition.

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Physiological properties of rat ventral pallidal neurons recorded intracellularly in vivo

Journal of Neurophysiology ◽

10.1152/jn.1996.75.4.1432 ◽

1996 ◽

Vol 75 (4) ◽

pp. 1432-1443 ◽

Cited By ~ 28

Author(s):

A. Lavin ◽

A. A. Grace

Keyword(s):

B Cells ◽

Nucleus Accumbens ◽

Action Potential ◽

Type A ◽

C Cells ◽

Postsynaptic Potentials ◽

A Cells ◽

Type C ◽

Stimulation Of

1. The physiology of ventral pallidal (VP) cells was investigated using in vivo intracellular recording and staining techniques in adult rats. Based on electrophysiological criteria, three different types of cells were found: type A cells, which fired phasic spikes that did not exhibit a substantial afterhyperpolarization (AHP), type B cells, which exhibited a slow ramplike depolarization that preceded the short-duration action potential; the spike was followed by a prominent AHP, and type C cells, which were the only cells that fired spikes in couplets or bursts, with the spikes in a burst exhibiting a progressive increase in duration and a decrease in amplitude. These cells also exhibited a rebound low threshold spikelike event. Furthermore, 18% of the VP cells recorded exhibited a slow subthreshold oscillation of the membrane potential (< 1 Hz). 2. The response of VP cells to stimulation of fibers arising from the prefrontal cortex, nucleus accumbens, and mediodorsal thalamic nucleus (MD) was examined. In contrast to our initial predictions, all cells responded to nucleus accumbens stimulation with excitation. Type A and B cells responded to nucleus accumbens stimulation with excitation and to MD stimulation with antidromic-like responses, orthodromic excitation, or evoked inhibitory postsynaptic potentials. Only type A cells responded to prefrontal cortical stimulation. Type C cells only responded to stimulation of the nucleus accumbens, which resulted in evoked excitatory postsynaptic potentials. 3. The cells in the VP therefore can be segregated into three physiologically defined groups according to action potential discharge patterns and their response to afferent fiber stimulation.

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In Vivo Stimulation of Insulin Secretion by Guanidine Derivatives in the Rat

Hormone and Metabolic Research ◽

10.1055/s-0028-1093873 ◽

1974 ◽

Vol 6 (02) ◽

pp. 115-120 ◽

Cited By ~ 8

Author(s):

A. Aynsley-Green ◽

K.G.M.M. Alberti

Keyword(s):

Insulin Secretion ◽

Guanidine Derivatives ◽

Stimulation Of

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Glucokinase in pancreatic B-cells and its inhibition by alloxan

Acta Endocrinologica ◽

10.1530/acta.0.1150021 ◽

1987 ◽

Vol 115 (1) ◽

pp. 21-29 ◽

Cited By ~ 34

Author(s):

Sigurd Lenzen ◽

Markus Tiedge ◽

Uwe Panten

Keyword(s):

Insulin Secretion ◽

B Cells ◽

B Cell ◽

Metabolic Flux ◽

Inhibitory Concentration ◽

Pancreatic B Cell ◽

High K ◽

Pancreatic B Cells ◽

Low K

Abstract. Characterization of glucokinase in pancreatic B-cells from ob/ob mice and from rat liver revealed identical characteristics. A narrow substrate specificity; high Km values for the two substrates, D-glucose and D-mannose, in the range of 10 and 20 mmol/l, respectively; higher Vmax values for D-glucose than for D-mannose; inhibition of glucokinase activities by D-mannoheptulose and by a specific glucokinase antibody. These characteristics distinguish glucokinase in soluble cytoplasmic fractions of pancreatic B-cells and liver from low Km hexokinases. Alloxan is a pancreatic B-cell cytotoxic agent, which has been widely used as a tool for the elucidation of the mechanisms of insulin secretion, because its inhibitory action on insulin secretion has been presumed to be intimately related to the mechanism of glucose-induced insulin secretion. Alloxan inhibited glucokinase but not hexokinase activity in cytoplasmic fractions of pancreatic B-cells and liver. The half maximal inhibitory concentration of alloxan was 5 μmol/l. Glucokinase activity was protected from alloxan toxicity only by D-glucose and D-mannose; the α anomer of D-glucose provided significantly greater protection than the β anomer. The non-metabolizable sugar 3-0-methyl-D-glucose did not provide protection of glucokinase activity against inhibition by alloxan. Thus, inhibition of pancreatic B-cell glucokinase may contribute to the inhibition of glucose-induced insulin secretion by alloxan. These results support the contention that glucokinase regulates the metabolic flux rate through the glycolytic chain in the pancreatic B-cell and thereby generates the signal for glucose-induced insulin secretion.

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BCR-mediated uptake of antigen linked to TLR9 ligand stimulates B-cell proliferation and antigen-specific plasma cell formation

Blood ◽

10.1182/blood-2008-10-185421 ◽

2009 ◽

Vol 113 (17) ◽

pp. 3969-3977 ◽

Cited By ~ 102

Author(s):

Julia Eckl-Dorna ◽

Facundo D. Batista

Keyword(s):

Cell Proliferation ◽

B Cells ◽

B Cell ◽

Plasma Cells ◽

Cell Formation ◽

Specific Class ◽

B Cell Differentiation ◽

Enhanced Production ◽

Stimulation Of

Abstract The activation of Toll-like receptor 9 (TLR9) expressed within B cells is associated with enhanced humoral immunity. However the role of TLR9 in the stimulation of B-cell responses, and more specifically in shaping the outcome of B-cell differentiation, remains unclear. Here, we observed that immunization with the TLR9 agonist CpG linked to protein antigen gave rise to enhanced production of antigen-specific class-switched antibodies in vivo. Unlike dendritic cells, B cells are unable to acquire these conjugates by macropinocytosis and instead depend on uptake through a signaling-competent B-cell receptor (BCR), provided the overall BCR-antigen avidity exceeds a defined threshold. The resultant stimulation of intrinsic TLR9 leads to enhanced antigen-specific B-cell proliferation and differentiation to form extrafollicular plasma cells. Thus, the direct conjugation of antigen and CpG reveals a mechanism that may operate during the initiation of primary immune responses, and may prove useful as a strategy for the design of adjuvants suitable for vaccinations.

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