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

Araújo, Ronaldo Carvalho; Mori, Marcelo A.; Merino, Vanessa F.; Bascands, Jean-Loup; Schanstra, Joost P.; Zollner, Ricardo de Lima; Villela, Conceição A.; Nakaie, Clóvis R.; Paiva, Antonio C.M.; Pesquero, Jorge L.; Bäder, Michael; Pesquero, João Bosco

doi:10.1515/bc.2006.057

Cited by 36 publications

(28 citation statements)

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“…Evidence that kinins induce insulin sensitivity in adipocytes (20) and control insulin released by pancreatic cells (21,22) indicates that the kallikrein-kinin system also participates in metabolic processes. However, the physiological relevance of this system to energy homeostasis and the contributions of the kinin B 1 receptor to these processes are still not well understood.…”

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confidence: 99%

Kinin B1 Receptor Deficiency Leads to Leptin Hypersensitivity and Resistance to Obesity

et al. 2008

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OBJECTIVE-Kinins mediate pathophysiological processes related to hypertension, pain, and inflammation through the activation of two G-protein-coupled receptors, named B 1 and B 2 . Although these peptides have been related to glucose homeostasis, their effects on energy balance are still unknown.RESEARCH DESIGN AND METHODS-Using genetic and pharmacological strategies to abrogate the kinin B 1 receptor in different animal models of obesity, here we present evidence of a novel role for kinins in the regulation of satiety and adiposity. RESULTS-Kinin B 1 receptor deficiency in mice (B 1Ϫ/Ϫ ) resulted in less fat content, hypoleptinemia, increased leptin sensitivity, and robust protection against high-fat diet-induced weight gain. Under high-fat diet, B 1 Ϫ/Ϫ also exhibited reduced food intake, improved lipid oxidation, and increased energy expenditure. Surprisingly, B 1 receptor deficiency was not able to decrease food intake and adiposity in obese mice lacking leptin (ob/ob-B 1 Ϫ/Ϫ ). However, ob/ob-B 1 Ϫ/Ϫ mice were more responsive to the effects of exogenous leptin on body weight and food intake, suggesting that B 1 receptors may be dependent on leptin to display their metabolic roles. Finally, inhibition of weight gain and food intake by B 1 receptor ablation was pharmacologically confirmed by long-term administration of the kinin B 1 receptor antagonist SSR240612 to mice under high-fat diet.CONCLUSIONS-Our data suggest that kinin B 1 receptors participate in the regulation of the energy balance via a mechanism that could involve the modulation of leptin sensitivity.

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Kinin B1 Receptor Deficiency Leads to Leptin Hypersensitivity and Resistance to Obesity

et al. 2008

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“…Ara ú jo et al (2006) verified that B1 -/-mice have pancreatic abnormalities, such as fewer islets of Langerhans and lower glucose-triggered insulin release. They also observed that the endogenous B1 agonist des-Arg9-bradykinin (DBK) stimulates insulin release in vivo in wild type mice by increasing pancreatic vascular permeability (Ara ú jo et al, 2006 ).…”

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confidence: 98%

Kinin B1 receptor gene ablation affects hypothalamic CART production^b

Torres¹,

Motta²,

Sales³

et al. 2013

Biological Chemistry

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Abstract:A role for the kinin B1 receptor in energy-homeostatic processes was implicated in previous studies; notably, the studies where kinin B1 receptor knockout mice (B1 -/-) were shown to have impaired adiposity, impaired leptin and insulin production, lower feed efficiency, protection from liver steatosis and diet-induced obesity when fed a high fat diet (HFD). In particular, in a model where the B1 receptor is expressed exclusively in the adipose tissue, it rescues the plasma insulin concentration and the weight gain seen in wild type mice. Taking into consideration that leptin participates in the formation of hypothalamic nuclei, which modulate energy expenditure, and feeding behavior, we hypothesized that these brain regions could also be altered in B1 -/-mice. We observed for the first time a difference in the gene expression pattern of cocaine and amphetamine related transcript (CART) in the (lateral hypothalamic area (LHA) resulting from the deletion of the kinin B1 receptor gene. The correlation between CART expression in the LHA and the thwarting of diet-induced obesity corroborates independent correlations between CART and obesity. Furthermore, it seems to indicate that the mechanism underlying the ' lean ' phenotype of B1 -/-mice does not stem solely from changes in peripheral tissues but may also receive contributions from changes in the hypothalamic machinery involved in energy homeostasis processes.

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“…In renal inflammatory conditions such as AKI, the kallikrein-kinin system (KKS) plays an important role in glucose homeostasis [5,6] . This system is also involved in kidney inflammatory and vasodilation processes [7] , which are directly involved in the inflammatory response mechanism of AKI.…”

Section: Introductionmentioning

confidence: 99%

Kinin B₂receptor does not exert renoprotective effects on mice with glycerol-induced rhabdomyolysis

Gattai¹

2014

WJN

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AIM:To investigate a potential protective role of the kinin B2 receptor in a glycerol-induced rhabdomyolysis mouse model. METHODS:We separated 28 C57Bl/6 male mice into 4 groups: untreated WT animals, untreated B2 knockout mice, glycerol-treated WT and glycerol-treated B2 knockout mice. Glycerol-treated animals received one intramuscular injections of glycerol solution (50% v/v, 7 mL/kg). After 48 h, urine and blood samples were collected to measure creatinine and urea levels. Additionally, kidney samples were extracted for histological evaluation, and the mRNA expression levels of kinin B1 and B2 receptors and inflammatory mediators were measured by real-time polymerase chain reaction. RESULTS:Serum creatinine and urea levels showed differences between untreated wild-type and glyceroltreated wild-type mice (0.66 ± 0.04 vs 2.61 ± 0.53 mg/dL, P < 0.01; and 33.51 ± 2.08 vs 330.2 ± 77.7 mg/dL, P < 0.005), and between untreated B2 knockout mice and glycerol-treated knockout mice (0.56 ± 0.03 vs 2.23 ± 0.87 mg/dL, P < 0.05; and 42.49 ± 3.2 vs 327.2 ± 58.4 mg/dL, P < 0.01), but there was no difference between the glycerol-treated wild-type and glycerol-treated knockout mice. Glycerol was able to induce a striking increase in kinin B2 receptor expression (> 30 times, 31.34 ± 8.9) in kidney. Animals injected with glycerol had a higher degree of tubular injury than untreated animals. Wild-type and knockout mice treated with glycerol intramuscularly present kidney injury, with impairment in renal function. However, B2 knockout mice treated with glycerol did not show a different phenotype regarding kidney injury markers, when compared to the wild-type glycerol-treated group. Gattai PP, Mafra FFP, Wasinski F, Almeida SS, Cenedeze MA, Malheiros DMAC, Bacurau RFP, Barros CC, Câmara NOS, Araujo RC. Kinin B2 receptor does not exert renoprotective effects on mice with glycerol-induced rhabdomyolysis. CONCLUSION: We conclude that the kinin B2 receptor

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

Cited by 36 publications

References 32 publications

Kinin B1 Receptor Deficiency Leads to Leptin Hypersensitivity and Resistance to Obesity

Kinin B1 Receptor Deficiency Leads to Leptin Hypersensitivity and Resistance to Obesity

Kinin B1 receptor gene ablation affects hypothalamic CART production^b

Kinin B₂receptor does not exert renoprotective effects on mice with glycerol-induced rhabdomyolysis

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

Cited by 36 publications

References 32 publications

Kinin B1 Receptor Deficiency Leads to Leptin Hypersensitivity and Resistance to Obesity

Kinin B1 Receptor Deficiency Leads to Leptin Hypersensitivity and Resistance to Obesity

Kinin B1 receptor gene ablation affects hypothalamic CART productionb

Kinin B2receptor does not exert renoprotective effects on mice with glycerol-induced rhabdomyolysis

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Product

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Kinin B1 receptor gene ablation affects hypothalamic CART production^b

Kinin B₂receptor does not exert renoprotective effects on mice with glycerol-induced rhabdomyolysis