scholarly journals A Fischer rat substrain deficient in dipeptidyl peptidase IV activity makes normal steady-state RNA levels and an altered protein. Use as a liver-cell transplantation model

1991 ◽  
Vol 273 (3) ◽  
pp. 497-502 ◽  
Author(s):  
N L Thompson ◽  
D C Hixson ◽  
H Callanan ◽  
M Panzica ◽  
D Flanagan ◽  
...  
Keyword(s):  
Dipeptidyl Peptidase ◽  
Cell Extract ◽  
Dipeptidyl Peptidase Iv ◽  
Northern Analysis ◽  
Fischer 344 Rats ◽  
Fischer 344 ◽  
D Cell ◽  
Fischer Rats ◽  
Kidney Liver ◽  
The U.S

Dipeptidyl peptidase IV (DPPIV) is a serine exoproteinase expressed at high levels in epithelial cells of kidney, liver and small intestine. Recently Watanabe, Kohima & Fujimoto [(1987) Experientia 43, 400-401] and Gossrau et al. [(1990) Histochem. J. 22, 172-173] reported that Fischer 344 rats are deficient in this enzyme. We have examined DPPIV expression in Fischer 344 rats available from U.S. and German suppliers and find that livers of the U.S. Fischer rats, in contrast with their German counterparts, express active DPPIV (D+). Northern analysis of liver RNA showed comparable levels of 3.4 kb and 5.6 kb DPPIV transcripts in both D+ rats from the U.S. and German (D-) rats. Monoclonal antibody (MAb) 236.3 to DPPIV immunoprecipitated at 150 kDa enzymically active (105 kDa, denatured) protein from surface-labelled D+ hepatocytes and reacted with canalicular and sinusoidal membranes (as shown by immunofluorescence microscopy). MAb 236.3 failed to immunoprecipitate a labelled peptide from D- cell extract or to stain D- liver sections. Polyclonal antibody (PAb) specific for DPPIV immunoprecipitated an enzymically active peptide from D+ hepatocyte extracts and a smaller, inactive peptide from D- hepatocyte extracts. Peptide maps of DPPIV immunoprecipitated from D+ extracts with MAb 236.3 and PAb were identical, but differed from that of the D- hepatocyte component recognized by PAb. The molecular basis of the DPPIV deficiency in the D- rats thus appears to be the translation of an enzymically inactive protein missing the epitope recognized by MAb 236.3. We have exploited these D- rats as hosts for syngeneic transplantation of liver cells from D+ Fischer rats. DPPIV expression is stable in the transplanted cells and allows them to be readily distinguished from the surrounding D- tissue.

NAD(P)H oxidase-generated superoxide anion accounts for reduced control of myocardial O2 consumption by NO in old Fischer 344 rats

2003 ◽  
Vol 285 (3) ◽  
pp. H1015-H1022 ◽  
Author(s):  
Alexandra Adler ◽  
Eric Messina ◽  
Ben Sherman ◽  
Zipping Wang ◽  
Harer Huang ◽  
...  
Keyword(s):  
Oxidant Stress ◽  
Heart Weight ◽  
Fischer 344 Rats ◽  
No Donor ◽  
Fischer 344 ◽  
Old Rats ◽  
Fischer Rats ◽  
Enos Protein

We investigated the role of nitric oxide (NO) in the control of myocardial O2 consumption in Fischer 344 rats. In Fischer rats at 4, 14, and 23 mo of age, we examined cardiac function using echocardiography, the regulation of cardiac O2 consumption in vitro, endothelial NO synthase (eNOS) protein levels, and potential mechanisms that regulate superoxide. Aging was associated with a reduced ejection fraction [from 75 ± 2%at4moto66 ± 3% ( P < 0.05) at 23 mo] and an increased cardiac diastolic volume [from 0.60 ± 0.04 to 1.00 ± 0.10 ml ( P < 0.01)] and heart weight (from 0.70 ± 0.02 to 0.90 ± 0.02 g). The NO-mediated control of cardiac O2 consumption by bradykinin or enalaprilat was not different between 4 mo (36 ± 2 or 34 ± 3%) and 14 mo (29 ± 1 or 25 ± 3%) but markedly ( P < 0.05) reduced in 23-mo-old Fischer rats (15 ± 3 or 7 ± 2%). The response to the NO donor S-nitroso- N-acetyl penicillamine was not different across groups (35%, 35%, and 44%). Interestingly, the eNOS protein level was not different at 4, 14, and 23 mo. The addition of tempol (1 mmol/l) to the tissue bath eliminated the depression in the control of cardiac O2 consumption by bradykinin (25 ± 3%) or enalaprilat (28 ± 3%) in 23-mo-old Fischer rats. We next examined the levels of enzymes involved in the production and breakdown of superoxide. The expression of Mn SOD, Cu/Zn SOD, extracellular SOD, and p67phox, however, did not differ between 4- and 23-mo-old rats. Importantly, there was a marked increase in gp91phox, and apocynin restored the defect in NO-dependent control of cardiac O2 consumption at 23 mo to that seen in 4-mo-old rats, identifying the role of NADPH oxidase. Thus increased biological activity of superoxide and not decreases in the enzyme that produces NO are responsible for the altered control of cardiac O2 consumption by NO in 23-mo-old Fischer rats. Increased oxidant stress in aging, by decreasing NO bioavailability, may contribute not only to changes in myocardial function but also to altered regulation of vascular tone and the progression of cardiac or vascular disease.

scholarly journals Interrelationship of dipeptidyl peptidase IV (DPP4) with the development of diabetes, dyslipidaemia and nephropathy: a streptozotocin-induced model using wild-type and DPP4-deficient rats

2008 ◽  
Vol 200 (1) ◽  
pp. 53-61 ◽  
Author(s):  
Yasushi Kirino ◽  
Youichi Sato ◽  
Takayuki Kamimoto ◽  
Kazuyoshi Kawazoe ◽  
Kazuo Minakuchi ◽  
...  
Keyword(s):  
Renal Function ◽  
Blood Glucose ◽  
Serum Creatinine ◽  
Dipeptidyl Peptidase ◽  
Dipeptidyl Peptidase Iv ◽  
Wild Type ◽  
Rat Strains ◽  
Kidney Weight ◽  
Kidney Liver

We examined the role of dipeptidyl peptidase IV (DPP4) in the development of diabetes, dyslipidaemia and renal dysfunction induced by streptozotocin (STZ). F344/DuCrlCrlj rats, which lack DPP4 activity, and wild-type rats were treated with STZ. Plasma DPP4 activity and biochemical parameters were measured until 42 days after STZ treatment. At the end of the experiment, renal function and DPP4 expressions of the kidney, liver, pancreas and adipose tissues were determined. Increases in blood glucose, cholesterol and triglycerides were evoked by STZ in both rat strains; however, the onset of hyperglycaemia was delayed in DPP4-deficient rats as compared with wild-type rats. By contrast, more severe dyslipidaemia was observed in DPP4-deficient rats than in wild-type rats after STZ treatment. Plasma DPP4 activity increased progressively with time after STZ treatment in wild-type rats. The kidney of wild-type rats showed decreased DPP4 activity with increased Dpp4 mRNA after STZ treatment. In addition, kidney weight, serum creatinine and excreted amounts of urinary protein, glucose and DPP4 enzyme were enhanced by STZ. DPP4-deficient rats showed increased serum creatinine in accordance with decreased creatinine clearance as compared with wild-type rats after STZ treatment. In conclusion, plasma DPP4 activity increased after STZ treatment, positively correlating to blood glucose. DPP4-deficient rats were resistant to developing diabetes, while susceptible to dyslipidaemia and reduction of glomerular filtration rate by STZ. DPP4 activation may be responsible for hyperglycaemia, lipid metabolism and preservation of renal function.

Immunocytochemical Demonstration of Insulin in Spontaneous Pancreatic Islet Cell Tumors of Fischer Rats

1983 ◽  
Vol 20 (3) ◽  
pp. 291-297 ◽  
Author(s):  
P. C. Stromberg ◽  
F. Wilson ◽  
C. C. Capen
Keyword(s):  
Pancreatic Islet ◽  
Islet Cell ◽  
Fischer 344 Rats ◽  
Islet Cell Tumors ◽  
Pancreatic Islet Cell ◽  
Fischer 344 ◽  
Pancreatic Islet Cell Tumors ◽  
Fischer Rats ◽  
Glucagon Immunoreactivity ◽  
F344 Rats

Nineteen spontaneous pancreatic islet cell tumors were studied in 26-month-old control Fischer 344 rats. Seventeen of 19 (89%) tumors demonstrated insulin reactivity using peroxidase-antiperoxidase immunocytochemistry. None of ten tumors had positive glucagon immunoreactivity. Immunocytochemical and ultrastructural observations suggested that spontaneous occurring islet cell tumors of F344 rats were composed exclusively of beta cells.

Diminished neurogenic but not pharmacological erections in the 2- to 3-month experimentally diabetic F-344 rat

1997 ◽  
Vol 272 (4) ◽  
pp. H1960-H1971 ◽  
Author(s):  
J. Rehman ◽  
E. Chenven ◽  
P. Brink ◽  
B. Peterson ◽  
B. Walcott ◽  
...  
Keyword(s):  
Erectile Function ◽  
Connexin 43 ◽  
Matched Control ◽  
Northern Analysis ◽  
Strongly Correlated ◽  
Fischer 344 Rats ◽  
Subtotal Pancreatectomy ◽  
Fischer 344 ◽  
Rapid Spread ◽  
Insulin Replacement

The rapid spread of locally restricted neural and hormonal signals among the vast array of largely inexcitable corporal smooth muscle cells is an absolute prerequisite to normal erectile function. And yet the mechanism(s) responsible for this phenomenon is not well understood. As a first step toward a more integrative understanding of erectile physiology and/or dysfunction, an 8- to 12-wk period of experimental diabetes was induced in 2-mo-old male Fischer 344 rats by either intraperitoneal streptozotocin (STZ) injection (35 mg/kg; n = 22) or subtotal pancreatectomy (n = 11). Fourteen age-matched control animals received injection of vehicle only while nine others served as sham-operated control animals. Eight STZ-diabetic animals received insulin replacement. Erectile function was assessed by evaluation of penile reflexes and monitoring of intracavernous pressure responses to both electrical stimulation of the cavernous nerve and intracorporal papaverine or nitroglycerin injection. Intracavernous pressure responses to neurostimulation were significantly attenuated in both STZ-diabetic and subtotal pancreatectomy animals compared with age-matched control animals (P < 0.05). Penile reflexes were also significantly diminished (P < 0.05). Regression analysis revealed that diabetes-related decreases in neurostimulated intracavernous pressure responses were strongly correlated with diminished synaptophysin immunoreactivity in the corpora (P < 0.001; r = 0.88). However, there were no detectable diabetes-related differences in pharmacological erections induced by intracavernous papaverine or nitroglycerin injection. Northern analysis revealed a marked diabetes-related increase in the amount of connexin 43 mRNA measured in frozen corporal tissue. Insulin replacement partially restored (attenuated the loss of) synaptophysin immunoreactivity and maintained neurostimulated intracavernous pressure responses to control levels while having no effect on penile reflexes. These observations may have important implications to the understanding of erectile physiology as well as the etiology of diabetes-related erectile dysfunction.

Improvement of high fat-diet-induced insulin resistance in dipeptidyl peptidase IV-deficient Fischer rats

Life Sciences ◽  
2002 ◽  
Vol 71 (2) ◽  
pp. 227-238 ◽  
Author(s):  
Nobuyuki Yasuda ◽  
Tadashi Nagakura ◽  
Kazuto Yamazaki ◽  
Takashi Inoue ◽  
Isao Tanaka
Keyword(s):  
Insulin Resistance ◽  
High Fat Diet ◽  
Dipeptidyl Peptidase ◽  
Dipeptidyl Peptidase Iv ◽  
High Fat ◽  
Fischer Rats

Improved Glucose Tolerance via Enhanced Glucose-Dependent Insulin Secretion in Dipeptidyl Peptidase IV-Deficient Fischer Rats

2001 ◽  
Vol 284 (2) ◽  
pp. 501-506 ◽  
Author(s):  
Tadashi Nagakura ◽  
Nobuyuki Yasuda ◽  
Kazuto Yamazaki ◽  
Hironori Ikuta ◽  
Seiji Yoshikawa ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Glucose Tolerance ◽  
Dipeptidyl Peptidase ◽  
Dipeptidyl Peptidase Iv ◽  
Fischer Rats

scholarly journals Organ distribution of aminopeptidase A and dipeptidyl peptidase IV in normal mice.

1996 ◽  
Vol 44 (5) ◽  
pp. 445-461 ◽  
Author(s):  
S Mentzel ◽  
H B Dijkman ◽  
J P Van Son ◽  
R A Koene ◽  
K J Assmann
Keyword(s):  
Solid Phase ◽  
Membranous Glomerulonephritis ◽  
Dipeptidyl Peptidase ◽  
Dipeptidyl Peptidase Iv ◽  
Organ Distribution ◽  
Molecular Weights ◽  
Brush Borders ◽  
Aminopeptidase A ◽  
Spleen And Lymph Nodes ◽  
Kidney Liver

The hydrolases aminopeptidase A and dipeptidyl peptidase IV, both present in the kidney on the brush borders of the proximal tubule epithelial cells and podocytes, are involved in the induction of experimental membranous glomerulonephritis in the mouse. However, little is known about their (co)distribution in other tissues and their function in health and disease. A detailed insight into the localization of these two enzymes is a prerequisite to elucidation of their function. Therefore, we investigated the presence and co-distribution of aminopeptidase A and dipeptidyl peptidase IV by immunohistology with two different rat monoclonal antibodies, the specificity of which was determined by an immunodepletion technique. In addition, the molecular weight of the hydrolases; was analyzed by SDS-PAGE after isolation by solid-phase immunoprecipitation from glomeruli, renal brush borders, and thymus. Both hydrolases showed different molecular weights in renal corpuscle, renal brush borders, and thymic cells. A widespread organ distribution of the two hydrolases was observed, with co-localization in kidney, liver, small intestine, thymus, brain, spleen, and lymph nodes, either on the same cells or on different cells in the same organ. This distribution and partial co-localization suggests that the two hydrolases, acting either alone or in concert, have a role in many diverse biological processes.

Human IL-1 receptor antagonist partially suppresses LPS fever but not plasma levels of IL-6 in Fischer rats

1992 ◽  
Vol 263 (3) ◽  
pp. R653-R655 ◽  
Author(s):  
B. K. Smith ◽  
M. J. Kluger
Keyword(s):  
Receptor Antagonist ◽  
Plasma Levels ◽  
Biological Effects ◽  
Interleukin 1 ◽  
Type I ◽  
Type Ii ◽  
Fischer 344 Rats ◽  
Fischer 344 ◽  
Fischer Rats

A human recombinant interleukin-1 receptor antagonist (IL-1ra) recognizes the two known IL-1 receptors and blocks the binding and many biological effects of both IL-1 alpha and IL-1 beta. The effectiveness of IL-1ra in modifying the fever and plasma IL-6 responses elicited by lipopolysaccharide (LPS) in vivo was tested in Fischer 344 rats. Animals that received IL-1ra 0.5 mg/kg intraperitoneally followed 10 min later by 10 micrograms/kg of LPS displayed significantly lower mean fever responses 2-4 h after injection than rats that received vehicle and LPS (0.48 +/- 0.13 vs. 0.95 +/- 0.16 degrees C, P = 0.016). Plasma levels of IL-6 at 4 h after injection were not different in IL-1ra-treated rats compared with controls (407,725 vs. 729,169 U/ml). Based on our previous finding that preadministration of antiserum to IL-1 beta markedly suppressed plasma IL-6 after LPS, and recent evidence that molar excesses of IL-1ra blocked IL-1-induced circulating IL-6 levels, the possibility that IL-1 is responsible for the induction of bioactive IL-6 during inflammation cannot be ruled out. Similarly, the inability of the IL-1ra to completely suppress the febrile responses of rats to LPS in the present study may be dose related. Alternatively, the induction of bioactive IL-6 by IL-1 in the rat may be mediated primarily through some receptor other than the type I (e.g., the type II receptor).

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