Role of the kinin B1 receptor in insulin homeostasis and pancreatic islet function

2006 ◽  
Vol 387 (4) ◽  
pp. 431-436 ◽  
Author(s):  
Ronaldo C. Araújo ◽  
Marcelo A. Mori ◽  
Vanessa F. Merino ◽  
Jean-Loup Bascands ◽  
Joost P. Schanstra ◽  
...  
Keyword(s):  
Vascular Permeability ◽  
Insulin Release ◽  
Serine Proteases ◽  
Tolerance Test ◽  
B1 Receptor ◽  
Subtype B ◽  
Insulin Tolerance ◽  
Kinin B1 Receptor ◽  
And Control

Abstract Kinins are potent vasoactive peptides generated in blood and tissues by the kallikrein serine proteases. Two distinct kinin receptors have been described, one constitutive (subtype B2) and one inducible (subtype B1), and many physiological functions have been attributed to these receptors, including glucose homeostasis and control of vascular permeability. In this study we show that mice lacking the kinin B1 receptor (B1 -/- mice) have lower fasting plasma glucose concentrations but exhibit higher glycemia after feeding when compared to wild-type mice. B1 -/- mice also present pancreas abnormalities, characterized by fewer pancreatic islets and lower insulin content, which leads to hypoinsulinemia and reduced insulin release after a glucose load. Nevertheless, an insulin tolerance test indicated higher sensitivity in B1 -/- mice. In line with this phenotype, pancreatic vascular permeability was shown to be reduced in B1 receptor-ablated mice. The B1 agonist desArg9bradykinin injected intravenously can induce the release of insulin into serum, and this effect was not observed in the B1 -/- mice or in isolated islets. Our data demonstrate the importance of the kinin B1 receptor in the control of pancreatic vascular homeostasis and insulin release, highlighting a new role for this receptor in the pathogenesis of diabetes and related diseases.

Abstract MP06: Kinin B1 Receptor Mediates Orexin System Hyperactivity In Salt-sensitive Hypertension

Hypertension ◽  
2020 ◽  
Vol 76 (Suppl_1) ◽  
Author(s):  
Rohan U Parekh ◽  
Abdel A Abdel-rahman ◽  
Srinivas Sriramula
Keyword(s):  
Radio Telemetry ◽  
Mrna Levels ◽  
Wild Type ◽  
Salt Treatment ◽  
Neurogenic Hypertension ◽  
B1 Receptor ◽  
Kinin B1 Receptor ◽  
Salt Sensitive Hypertension ◽  
The Brain

Hyperactivity of the orexin system contributes to several animal models of hypertension and enhances arginine vasopressin (AVP) release. We previously reported higher neuronal kinin B1 receptor (B1R) expression and brain AVP levels in hypertensive mice. However, the role of B1R and its interaction with orexin system in neurogenic hypertension have not been studied. In the present study, we tested the hypothesis that kinin B1R contributes to hypertension by upregulation of orexin-AVP signaling in the brain. Deoxycorticosterone acetate (DOCA)-salt treatment (1 mg/g body weight DOCA, 1% saline in drinking water, 3 weeks) of wild-type (WT) male mice produced a significant increase in mean arterial pressure (MAP; radio-telemetry) (138 ±3 mmHg, n=8, p<0.01) that was blunted in B1R knockout mice (121±2 mmHg, P <0.05 vs. WT+DOCA). In WT mice, DOCA-salt, compared to vehicle, increased mRNA levels of orexin receptor 1 (2.5 fold, n=9, p<0.001), orexin receptor 2 (3 fold, n=9, p<0.001) and AVP (3 fold, n=9, p<0.01) in the hypothalamic paraventricular nucleus (PVN), and these DOCA-salt evoked effects were attenuated in B1RKO mice. Similarly, DOCA-salt evoked increases in protein expression of orexin receptor 1 and 2 in the hypothalamic PVN of WT mice were attenuated by 25±5% and 33±5% (p<0.05), respectively, in B1RKO vs WT+DOCA mice. Furthermore, DOCA-salt treatment increased plasma AVP levels in WT mice compared to vehicle treated mice (13.69±1.1 vs. 47.86±8.7 pg/ml, p<0.05), but not in B1RKO mice. Together, these data provide novel evidence that kinin B1R plays an important role in mediating DOCA-salt induced hypertension possibly via upregulating the orexin-AVP signaling in the brain.

Emerging role of microglial kinin B1 receptor in diabetic pain neuropathy

2012 ◽  
Vol 234 (2) ◽  
pp. 373-381 ◽  
Author(s):  
Sébastien Talbot ◽  
Réjean Couture
Keyword(s):  
B1 Receptor ◽  
Kinin B1 Receptor

Insulin and Blood Fibrinolytic Activity

1973 ◽  
Vol 29 (02) ◽  
pp. 293-299 ◽  
Author(s):  
Anne M Hedlin
Keyword(s):  
Glucose Tolerance ◽  
Fibrinolytic Activity ◽  
Glucose Tolerance Test ◽  
Tolerance Test ◽  
Control Subjects ◽  
Insulin Tolerance ◽  
Hospital Patients ◽  
Blood Lysis ◽  
And Control ◽  
Increased Activity

SummaryThe effect of insulin on fibrinolysis was studied in hospital patients who were subjected to an insulin tolerance or glucose tolerance test. Blood samples were obtained at frequent intervals over a 2-3 hour period and fibrinolytic activity determined by the dilute whole blood lysis test. Normal control subjects were tested in both fasting and in non-fasting states. A marked increase in fibrinolytic activity was produced during the insulin tolerance test. However, as this increase did not appear until the blood glucose had been reduced to 30-40 mg % it was considered to be due, not to the insulin which had been administered, but rather to the action of those hormones which would be released in response to the hypoglycemia. On the other hand, the results of the glucose tolerance test demonstrated a gradual increase in fibrinolysis during the test period. Again this increased activity could not be attributed to the action of insulin because a similar effect was apparent in the samples obtained from the control subjects. Therefore, it was concluded that the enhancement of fibrinolysis observed in both test and control subjects was not due to the action of insulin.

Role of Nuclear Factor-κB and Protein Kinase C Signaling in the Expression of the Kinin B1 Receptor in Human Vascular Smooth Muscle Cells

2006 ◽  
Vol 71 (3) ◽  
pp. 949-956 ◽  
Author(s):  
Marie Eve Moreau ◽  
Marie-Thérèse Bawolak ◽  
Guillaume Morissette ◽  
Albert Adam ◽  
François Marceau
Keyword(s):  
Smooth Muscle ◽  
Protein Kinase C ◽  
Protein Kinase ◽  
Vascular Smooth Muscle Cells ◽  
Nuclear Factor Κb ◽  
Nuclear Factor ◽  
B1 Receptor ◽  
Kinase C ◽  
Kinin B1 Receptor

scholarly journals Kinin B1 Receptor Up-Regulation after Lipopolysaccharide Administration: Role of Proinflammatory Cytokines and Neutrophil Influx

2004 ◽  
Vol 172 (3) ◽  
pp. 1839-1847 ◽  
Author(s):  
Giselle F. Passos ◽  
Elizabeth S. Fernandes ◽  
Maria M. Campos ◽  
José G. V. C. Araújo ◽  
Jorge L. Pesquero ◽  
...  
Keyword(s):  
Proinflammatory Cytokines ◽  
Neutrophil Influx ◽  
B1 Receptor ◽  
Kinin B1 Receptor

The emerging role of serine proteases in apoptosis

2007 ◽  
Vol 35 (3) ◽  
pp. 559-560 ◽  
Author(s):  
K.L. Moffitt ◽  
S.L. Martin ◽  
B. Walker
Keyword(s):  
Cell Death ◽  
Late Stage ◽  
Serine Proteases ◽  
Dna Degradation ◽  
Predominant Role ◽  
Disease States ◽  
Nuclear Events ◽  
Proteolytic Activities ◽  
And Control

Unregulated apoptosis can be due to a disruption in the balance and control of both intra- and inter-cellular proteolytic activities leading to various disease states. Many proteases involved in apoptotic processes are yet to be identified; however, several are already well characterized. Caspases traditionally held the predominant role as prime mediators of execution. However, latterly, evidence has accumulated that non-caspases, including calpains, cathepsins, granzymes and the proteasome have roles in mediating and promoting cell death. Increasingly, research is implicating serine proteases within apoptotic processing, particularly in the generation of nuclear events such as condensation, fragmentation and DNA degradation observed in late-stage apoptosis. Serine proteases therefore are emerging as providing additional or alternative therapeutic targets.

scholarly journals Are There Sex Differences in the Reaction of Undercarboxylated Osteocalcin to Hypoglycemia?

2020 ◽  
pp. S315-S320
Author(s):  
M. DUŠKOVÁ ◽  
L. KOLÁTOROVÁ ◽  
H. JANDÍKOVÁ ◽  
H. POSPÍŠILOVÁ ◽  
L. STÁRKA
Keyword(s):  
Glucose Metabolism ◽  
Tolerance Test ◽  
Undercarboxylated Osteocalcin ◽  
New Bone Formation ◽  
Time Intervals ◽  
Insulin Tolerance ◽  
Interesting Difference ◽  
Regular Time ◽  
Endocrine Organs

There has been increasing evidence in recent years for the hypothesis of bones as endocrine organs. Osteocalcin, long considered just a marker of new bone formation, is now seen as the first hormone produced by bones, and seems to be associated with regulating glucose metabolism and reproduction. The aim of this work was to monitor changes of osteocalcin in reaction to hypoglycemia, and determine if there are differences in such reactions between the sexes. The study included 61 healthy probands with physiological calciophosphate metabolism (30 men and 31 women). We applied to each of them an insulin tolerance test, and then monitored levels of undercarboxylated osteocalcin and reactions to hypoglycemia at regular time intervals. We found differences in the reaction to hypoglycemia between the sexes. In men there was a significant decline in undercarboxylated osteocalcin between the 30 and 40 min (p<0.0015), which reflects a reaction to a glycemic decline between 25-30 min, followed by reversal. Low undercarboxylated osteocalcin in men lasted up to 90 min, after which they returned to levels before the test. In women we did not find any significant changes in undercarboxylated osteocalcin levels. Changes in undercarboxylated osteocalcin induced by hypoglycemia indicate a relationship between bones and glucose metabolism. There was an interesting difference between the sexes. However, a definitive conclusion about the role of osteocalcin in human metabolism will require numerous future studies.

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