Bradykinin enhances GLUT4 translocation through the increase of insulin receptor tyrosine kinase in primary adipocytes: evidence that bradykinin stimulates the insulin signalling pathway

Isami, S.; Kishikawa, Hiroki; Araki, Eiichi; Uehara, Masayuki; Kaneko, Katsuya; Shirotani, Tetsuya; Todaka, Mikio; Ura, S.; Motoyoshi, S.; Matsumoto, Kazuya; Miyamura, Nobuhiro; Shichiri, Motoaki

doi:10.1007/bf00400672

Cited by 66 publications

(49 citation statements)

References 40 publications

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“…Because the kinin-kallikrein system is involved in sensitizing insulin action in peripheral tissues, 29,30 it is possible that the increased activity of tissue ACE leads to insulin resistance through the decrease of kallikrein levels. However, Dahl-S rats fed a normal diet demonstrated lower plasma and tissue angiotensin II than Dahl-R rats, but salt loading did not cause significant changes in angiotensin II levels in either strain.…”

Section: Discussionmentioning

confidence: 99%

High-Salt Diet Enhances Insulin Signaling and Induces Insulin Resistance in Dahl Salt-Sensitive Rats

et al. 2002

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Abstract-A high-salt diet, which is known to contribute to the pathogenesis of hypertension, is also reportedly associated with insulin resistance. We investigated the effects of a high-salt diet on insulin sensitivity and insulin signaling in salt-sensitive (Dahl-S) and salt resistant (Dahl-R) strains of the Dahl rat. Evaluation of hyperinsulinemic-euglycemic clamp studies and glucose uptake into the isolated soleus muscle revealed that salt loading (8% NaCl) for 4 weeks induced hypertension and significant insulin resistance in Dahl-S rats, whereas no significant effects were observed in Dahl-R rats. Despite the presence of insulin resistance, insulin-induced tyrosine phosphorylation of the insulin receptor and insulin receptor substrates, activation of phosphatidylinositol 3-kinase, and phosphorylation of Akt were all enhanced in Dahl-S rats fed a high-salt diet. The mechanism underlying this form of insulin resistance thus differs from that previously associated with obesity and dexamethasone and is likely due to the impairment of one or more metabolic steps situated downstream of phosphatidylinositol 3-kinase and Akt activation. Interestingly, supplementation of potassium (8% KCl) ameliorated the changes in insulin sensitivity in Dahl-S rats fed a high-salt diet; this was associated with a slight but significant decrease in blood pressure. Evidence presented suggest that there is an interdependent relationship between insulin sensitivity and salt sensitivity of blood pressure in Dahl-S rats, and it is suggested that supplementing the diet with potassium may exert a protective effect against both hypertension and insulin resistance in salt-sensitive individuals.

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Section: Discussionmentioning

confidence: 99%

High-Salt Diet Enhances Insulin Signaling and Induces Insulin Resistance in Dahl Salt-Sensitive Rats

et al. 2002

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“…10,11 In the absence of BKB2R, mice showed normal insulin sensitivity but reduced glucose tolerance (Figures 1a-f). Additionally, 6-month-old obB2KO mice displayed a higher fasting hyperglycemia when compared with obWT (162.3±28.2 mg/dl vs 85.25±13.3 mg/dl, Figure 1g).…”

Section: Bkb2r Deficiency Potentiates Hyperglycemia and Reduces Glucomentioning

confidence: 99%

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confidence: 99%

“…In isolated systems, it has been shown that BK can trigger the translocation of the glucose transporter 4 (GLUT4) in adipose tissue and muscle either directly 8 or by increasing insulin sensitivity. [10][11][12] Miyata et al 11 showed that BK can promote insulin action, augmenting both the phosphorylation of the insulin receptor and the insulin receptor substrate-1 in skeletal muscle and rat L6 myoblasts. Kishi et al 8 concluded that BK increases GLUT4 translocation in three different cell lines (L6 myotubes, 3T3-L1 adipocytes and CHO) independently on insulin.…”

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Bradykinin inhibits hepatic gluconeogenesis in obese mice

Barros

Haro

Russo

et al. 2012

Laboratory Investigation

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The kallikrein-kinin system (KKS) has been previously linked to glucose homeostasis. In isolated muscle or fat cells, acute bradykinin (BK) stimulation was shown to improve insulin action and increase glucose uptake by promoting glucose transporter 4 translocation to plasma membrane. However, the role for BK in the pathophysiology of obesity and type 2 diabetes remains largely unknown. To address this, we generated genetically obese mice (ob/ob) lacking the BK B2 receptor (obB2KO). Despite similar body weight or fat accumulation, obB2KO mice showed increased fasting glycemia (162.3±28.2 mg/dl vs 85.3±13.3 mg/dl), hyperinsulinemia (7.71±1.75 ng/ml vs 4.09±0.51 ng/ml) and impaired glucose tolerance when compared with ob/ob control mice (obWT), indicating insulin resistance and impaired glucose homeostasis. This was corroborated by increased glucose production in response to a pyruvate challenge. Increased gluconeogenesis was accompanied by increased hepatic mRNA expression of forkhead box protein O1 (FoxO1, four-fold), peroxisome proliferator-activated receptor gamma co-activator 1-alpha (seven-fold), phosphoenolpyruvate carboxykinase (PEPCK, three-fold) and glucose-6-phosphatase (eight-fold). FoxO1 nuclear exclusion was also impaired, as the obB2KO mice showed increased levels of this transcription factor in the nucleus fraction of liver homogenates during random feeding. Intraportal injection of BK in lean mice was able to decrease the hepatic mRNA expression of FoxO1 and PEPCK. In conclusion, BK modulates glucose homeostasis by affecting hepatic glucose production in obWT. These results point to a protective role of the KKS in the pathophysiology of type 2 diabetes mellitus. KEYWORDS: bradykinin; gluconeogenesis; kinin receptor; leptin; ob/ob; obesity The pathophysiology of type 2 diabetes mellitus (T2DM) involves innumerous metabolic and endocrine alterations, including changes in the carbohydrate, lipid and protein metabolisms. T2DM is directly linked with insulin resistance and the inability of pancreatic beta cells to compensate for these changes. 1 There is also a strong association between T2DM and obesity 1,2 that persists independently of gender or ethnic group. In this interaction, the weight gain of obese subjects seems to precede the development of T2DM. 3 Kinins are vasoactive peptides produced in the circulatory system and other tissues by the action of serine proteases called kallikreins. The kallikrein-kinin system (KKS) modulates pain, vasodilatation, vascular permeability, inflammation and edema and has been linked to insulin resistance. [4][5][6][7] Bradykinin (BK), the agonist of the constitutively expressed BK B2 receptor (BKB2R), has been reported to increase glucose uptake in skeletal muscle and adipose tissue. 8 At the same time, the kinin B1 receptor and its agonist, the des-arg 9 -kinin, have been shown to control leptin sensitivity 7 and insulin secretion. 9 Despite evidence that acute BK stimulation improves glucose uptake, the role for BK and BKB2R in the pathophysiology of T2DM is s...

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“…Bradykinin also increases glucose uptake in muscular cells and primary adipocytes by triggering GLUT4 (SLC2A4) translocation through insulin-dependent and -independent pathways (Isami et al 1996, Kishi et al 1998, Beard et al 2006. However, in humans, the effect of kinins on muscle glucose uptake remains controversial , Nuutila et al 1996, Mahajan et al 2004.…”

Section: Introductionmentioning

confidence: 99%

Tissue kallikrein deficiency, insulin resistance, and diabetes in mouse and man

Potier¹,

Waeckel²,

Fumeron³

et al. 2014

Journal of Endocrinology

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The kallikrein-kinin system has been suggested to participate in the control of glucose metabolism. Its role and the role of angiotensin-I-converting enzyme, a major kinininactivating enzyme, are however the subject of debate. We have evaluated the consequence of deficiency in tissue kallikrein (TK), the main kinin-forming enzyme, on the development of insulin resistance and diabetes in mice and man. Mice with inactivation of the TK gene were fed a high-fat diet (HFD) for 3 months, or crossed with obese, leptindeficient (ob/ob) mice to generate double ob/ob-TK-deficient mutants. In man, a loss-offunction polymorphism of the TK gene (R53H) was studied in a large general population cohort tested for insulin resistance, the DESIR study (4843 participants, 9 year follow-up). Mice deficient in TK gained less weight on the HFD than their WT littermates. Fasting glucose level was increased and responses to glucose (GTT) and insulin (ITT) tolerance tests were altered at 10 and 16 weeks on the HFD compared with standard on the diet, but TK deficiency had no influence on these parameters. Likewise, ob-TK K/K mice had similar GTT and ITT responses to those of ob-TK C/C mice. TK deficiency had no effect on blood pressure in either model. In humans, changes over time in BMI, fasting plasma glucose, insulinemia, and blood pressure were not influenced by the defective 53H-coding TK allele. The incidence of diabetes was not influenced by this allele. These data do not support a role for the TK-kinin system, protective or deleterious, in the development of insulin resistance and diabetes.

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Bradykinin enhances GLUT4 translocation through the increase of insulin receptor tyrosine kinase in primary adipocytes: evidence that bradykinin stimulates the insulin signalling pathway

Cited by 66 publications

References 40 publications

High-Salt Diet Enhances Insulin Signaling and Induces Insulin Resistance in Dahl Salt-Sensitive Rats

High-Salt Diet Enhances Insulin Signaling and Induces Insulin Resistance in Dahl Salt-Sensitive Rats

Bradykinin inhibits hepatic gluconeogenesis in obese mice

Tissue kallikrein deficiency, insulin resistance, and diabetes in mouse and man

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