Lysosomal Degradation of Receptor-bound 125I-labeled Insulin by Rat Adipocytes: Its Characterization and Dissociation from the Short-term Biologic Effects of Insulin

Abstract Macrothrombocytopenia in MYH9-related disease (MYH9-RD) results from defects in nonmuscular myosin-IIA function. Thrombopoietin receptor agonists (eltrombopag; romiplostim) seem to improve hemostasis, but little is known about their biologic effects in MYH9-RD. We administered romiplostim to Myh9−/− mice (100 μg/kg, every 3 days, during 1 month). MKs increased to similar numbers in Myh9−/− and wild-type (WT) mice (with an increase in immature MKs), but Myh9−/− platelet count response was much less (2.5-fold vs 8-fold increase). A strong increase in MK nuclei emboli in the lung, in WT and Myh9−/− mice, indicates increased transmigration of MKs from the BM. Prolonged (but not acute) treatment with romiplostim decreased expression of GPIb-IX-V complex and GPVI, but not of GPIIbIIIa, and bleeding time increased in WT mice. Microcirculation was not altered by the increased number of large platelets in any of the assessed organs, but in Myh9−/− mice a much stronger increase in BM reticulin fibers was present after 4 weeks of romiplostim treatment vs WT mice. These data further encourage short-term use of thrombopoietic agents in patients with MYH9-RDs; however, myelofibrosis has to be considered as a potential severe adverse effect during longer treatment. Reduction of GPIbIX/GPVI expression by romiplostim requires further studies.

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Short-term control of the pentose phosphate cycle by insulin could be modulated by the NADPHNADP ratio in rat adipocytes and hepatocytes

Biochemical and Biophysical Research Communications ◽

10.1016/0006-291x(87)90618-8 ◽

1987 ◽

Vol 146 (2) ◽

pp. 920-925 ◽

Cited By ~ 33

Author(s):

Isabel Fabregat ◽

Elisa Revilla ◽

Alberto Machado

Keyword(s):

Pentose Phosphate ◽

Short Term ◽

Rat Adipocytes ◽

Pentose Phosphate Cycle

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Short-term effects of palmitate and 2-bromopalmitate on the lipolytic activity of rat adipocytes

Life Sciences ◽

10.1016/j.lfs.2011.07.010 ◽

2011 ◽

Vol 89 (13-14) ◽

pp. 450-455 ◽

Cited By ~ 5

Author(s):

Tomasz Szkudelski ◽

Katarzyna Szkudelska

Keyword(s):

Lipolytic Activity ◽

Short Term ◽

Rat Adipocytes ◽

Short Term Effects

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Investigation into the role of dopamine and lysosomes in the impairment of prolactin transformation and release imposed by long periods of non-suckling in the rat

Acta Endocrinologica ◽

10.1530/acta.0.1140371 ◽

1987 ◽

Vol 114 (3) ◽

pp. 371-378 ◽

Cited By ~ 2

Author(s):

F. Mena ◽

G. Martinez-Escalera ◽

C. Clapp ◽

D. Aguayo ◽

M. T. Morales ◽

...

Keyword(s):

Incubation Medium ◽

Anterior Pituitary ◽

Suckling Period ◽

Lysosomal Degradation ◽

Transformation Mechanism ◽

Short Term ◽

In Vitro Transformation

Abstract. The transformation of prolactin (PRL) within lactating rat hemipituitary glands incubated for 240 min and the release of the hormone into the incubation medium were progressively reduced by dopamine added to the medium over a 2.3–49 μmol/l range of concentration; the antilysosomal drug chloroquine did not alter these effects of dopamine. In related experiments, the short-term action of dopamine was manifested also upon in vitro transformation, repletion and release of in vivo labelled [3H]PRL, thus indicating that dopamine inhibits all phases of PRL secretion by the lactating rat anterior pituitary (AP). In other experiments, increasing the non-suckling period from 8 to 16 h reduced the pre-suckled concentration of PRL in the lactating rat AP, reduced the ability of the AP to transform PRL in response to suckling, and reduced the capability of the AP of such rats to secrete PRL in vitro. Injecting chloroquine (0.2 mmol/kg ip), haloperidol (0.27 μmol/kg ip) or providing 15–30 min of suckling midway during the 16-h non-suckling period restored each of these functions. Thus, frequent uncoupling of dopamine from its receptor appears necessary to prevent impairment of the suckling-induced transformation mechanism in the lactating rat AP and, presumably, to prevent PRL in the lactotrope from reaching an age where it becomes susceptible to lysosomal degradation.

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The biologic properties of recombinant human thrombopoietin in the proliferation and megakaryocytic differentiation of acute myeloblastic leukemia cells

Blood ◽

10.1182/blood.v88.8.3074.bloodjournal8883074 ◽

1996 ◽

Vol 88 (8) ◽

pp. 3074-3082 ◽

Cited By ~ 25

Author(s):

I Matsumura ◽

Y Kanakura ◽

T Kato ◽

H Ikeda ◽

Y Horikawa ◽

...

Keyword(s):

Growth Response ◽

Acute Myeloblastic Leukemia ◽

Leukemia Cells ◽

Short Term ◽

Megakaryocytic Differentiation ◽

Biologic Effects ◽

French American British ◽

Short Term Culture ◽

Recombinant Human Thrombopoietin

Thrombopoietin (TPO) is implicated as a primary regulator of megakaryopoiesis and thrombopoiesis. However, the biologic effects of TPO on human acute myeloblastic leukemia (AML) cells are largely unknown. To determine if recombinant human (rh) TPO has proliferation-supporting and differentiation-inducing activities in AML cells, 15 cases of AML cells that were exclusively composed of undifferentiated leukemia cells and showed growth response to rhTPO in a short-term culture (72 hours) were subjected to long-term suspension culture with or without rhTPO. Of 15 cases, rhTPO supported proliferation of AML cells for 2 to 4 weeks in 4 cases whose French-American-British subtypes were M0, M2, M4, and M7, respectively. In addition to the proliferation-supporting activity, rhTPO was found to induce AML cells to progress to some degree of megakaryocytic differentiation at both morphologic and surface-phenotypic level in 2 AML cases with M0 and M7 subtypes. The treatment of AML cells with rhTPO resulted in rapid tyrosine phosphorylation of the TPO-receptor, c-mpl, and STAT3 in all of cases tested. By contrast, the expression of erythroid/megakaryocyte-specific transcription factors (GATA-1, GATA-2, and NF-E2) was markedly induced or enhanced in only 2 AML cases that showed megakaryocytic differentiation in response to rhTPO. These results suggested that, at least in a fraction of AML cases, TPO could not only support the proliferation of AML cells irrespective of AML subtypes, but could also induce megakaryocytic differentiation, possibly through activation of GATA-1, GATA-2, and NF-E2.

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Short-Term Regulation of Adiponectin Secretion in Rat Adipocytes

Physiological Research ◽

10.33549/physiolres.931971 ◽

2011 ◽

pp. 521-530 ◽

Cited By ~ 14

Author(s):

T. SZKUDELSKI ◽

L. NOGOWSKI ◽

K. SZKUDELSKA

Keyword(s):

Electron Transport ◽

Metabolic Diseases ◽

Biologically Active ◽

Dibutyryl Camp ◽

Short Term ◽

Rat Adipocytes ◽

Adenosine A1 ◽

A1 Receptor ◽

Active Substances ◽

Isolated Rat

Adiponectin belongs to the group of biologically active substances secreted by adipocytes and referred to as adipokines. Disturbances in its secretion and/or action are thought to be involved in the pathogenesis of some metabolic diseases. However, regulation of adiponectin secretion is poorly elucidated. In the present study, short-term regulation of adiponectin secretion in primary rat adipocytes was investigated. Isolated rat adipocytes were incubated in Krebs-Ringer buffer containing 5 mM glucose and insulin alone or in the combination with epinephrine, dibutyryl-cAMP, adenosine A1 receptor antagonist (DPCPX), palmitate, 2-bromopalmitate or inhibitor of mitochondrial electron transport (rotenone). Adipocyte exposure for 2 h to insulin (1-100 nM) significantly increased secretion of adiponectin compared with secretion observed without insulin. Furthermore, secretion of adiponectin from adipocytes incubated with glucose and insulin was reduced by 1 and 2 μM epinephrine, but not by 0.25 and 0.5 μM epinephrine. Under similar conditions, 1 and 2 mM dibutyryl-cAMP substantially diminished secretion of adiponectin, whereas 0.5 mM dibutyryl-cAMP was ineffective. Secretion of adiponectin was found to be effectively decreased by DPCPX. Moreover, adipocyte exposure to rotenone also resulted in a substantial diminution of secretory response of adipocytes incubated for 2 h with glucose and insulin. It was also demonstrated that palmitate and 2-bromopalmitate (0.06-0.5 mM) failed to affect secretion of leptin. The obtained results indicated that in short-term regulation of adiponectin secretion, insulin and epinephrine exert the opposite effects. These effects appeared as early as after 2 h of exposure. Moreover, deprivation of energy or blockade of adenosine action substantially decreased secretion of adiponectin.

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