Inorganic nitrite stimulates pancreatic islet blood flow and insulin secretion

Nyström, Thomas; Ortsäter, Henrik; Zhen, Huang; Zhang, Fan; Larsen, Filip J.; Weitzberg, Eddie; Lundberg, Jon O.; Sjöholm, Åke

doi:10.1016/j.freeradbiomed.2012.06.031

Cited by 81 publications

(72 citation statements)

References 34 publications

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“…The experiments were performed according to a protocol previously described in detail [10][11][12][13][14][15][16][17][18]. Non-fasting rats were anaesthetized with an intraperitoneal injection of thiobutabarbital sodium (120 mg/kg of body weight; Inactin TM , Research Biochemicals International), and placed on a heated operating table to maintain the body temperature.…”

Section: Blood Flow Measurementsmentioning

confidence: 99%

“…Both of these substances were dissolved in saline. These treatment conditions (time period and concentrations) were chosen based upon previous publications [4,7,[11][12][13][14][15][16][17][18]24] and recommendations from the drug provider. An advantage of this acute setting, over chronic treatment, is that non-specific changes due to alterations in, for example, body weight does not confound the outcome.…”

Section: Blood Flow Measurementsmentioning

confidence: 99%

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Acute regulation of pancreatic islet microcirculation and glycaemia by telmisartan and ramipril: discordant effects between normal and Type 2 diabetic rats

et al. 2013

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Diabetic patients are often treated with an ACEi (angiotensin-converting enzyme inhibitor) or angiotensin receptor antagonist against hypertension or albuminuria. These drugs also have a positive impact on glucose tolerance, but the mechanism for this remains elusive. Hypothesizing a positive non-additive effect, we studied whether the angiotensin receptor antagonist telmisartan or the ACEi ramipril acutely influence insulin secretion and glycaemia in vivo in healthy and Type 2 diabetic rats through effects on islet blood perfusion. Telmisartan and ramipril were injected intravenously into anaesthetized non-diabetic Wistar rats or Type 2 diabetic GK (Goto-Kakizaki) rats. In non-diabetic Wistar rats, neither whole PBF (pancreatic blood flow) nor IBF (islet blood flow) were significantly influenced by telmisartan and ramipril, alone or in combination. Renal blood flow was enhanced significantly by telmisartan and ramipril when used in combination, whereas ABF (adrenal blood flow) was not affected by any of the drugs. Telmisartan and ramipril both significantly increased serum insulin levels, but did not influence glycaemia. In Type 2 diabetic GK rats, both whole PBF and IBF were significantly decreased by telmisartan and ramipril, but only when used in combination. Renal blood flow was enhanced significantly by telmisartan and ramipril alone, but not when used in combination, whereas ABF was not affected by any of the drugs. Telmisartan and ramipril both significantly decreased serum insulin levels, and non-additively elevated blood glucose levels. In conclusion, the present study suggests that a local pancreatic RAS (renin-angiotensin system), sensitive to acute administration of telmisartan and ramipril, controls pancreatic IBF and insulin secretion and thereby has an impact on glucose tolerance. Our findings indicate unexpected significant differences in the effects of these agents on islet microcirculation, in vivo insulin secretion and glycaemia between healthy and Type 2 diabetic rats.

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Section: Blood Flow Measurementsmentioning

confidence: 99%

Section: Blood Flow Measurementsmentioning

confidence: 99%

Acute regulation of pancreatic islet microcirculation and glycaemia by telmisartan and ramipril: discordant effects between normal and Type 2 diabetic rats

et al. 2013

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“…Moreover, renin-angiotensin system (RAS) inhibitors that regulate the islet blood flow, such as ACE inhibitors and angiotensin II receptor blockers (ARBs), increased insulin secretion in response to glucose administration (8)(9)(10). In addition to RAS inhibitors, some vasoactive drugs enhance pancreatic islet blood flow, augment insulin secretion, and improve glucose tolerance (11,12).…”

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confidence: 99%

Insulin Receptor Substrate-2 (Irs2) in Endothelial Cells Plays a Crucial Role in Insulin Secretion

et al. 2014

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Endothelial cells are considered to be essential for normal pancreatic β-cell function. The current study attempted to demonstrate the role of insulin receptor substrate-2 (Irs2) in endothelial cells with regard to insulin secretion. Endothelial cell–specific Irs2 knockout (ETIrs2KO) mice exhibited impaired glucose-induced, arginine-induced, and glucagon-induced insulin secretion and showed glucose intolerance. In batch incubation and perifusion experiments using isolated islets, glucose-induced insulin secretion was not significantly different between the control and the ETIrs2KO mice. In contrast, in perfusion experiments, glucose-induced insulin secretion was significantly impaired in the ETIrs2KO mice. The islet blood flow was significantly impaired in the ETIrs2KO mice. After the treatment of these knockout mice with enalapril maleate, which improved the islet blood flow, glucose-stimulated insulin secretion was almost completely restored to levels equal to those in the control mice. These data suggest that Irs2 deletion in endothelial cells leads to a decreased islet blood flow, which may cause impaired glucose-induced insulin secretion. Thus, Irs2 in endothelial cells may serve as a novel therapeutic target for preventing and ameliorating type 2 diabetes and metabolic syndrome.

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“…On the other hand, mice with the eNOS gene knockout were shown to develop a metabolic syndrome-like phenotype, which could be prevented by dietary NO 3 -supplementation [46]. It has also been demonstrated that, at least in rats, NO 3 -and NO 2 -increase pancreatic insulin secretion [47], which altogether suggests that NO and insulin mutually stimulate their generation. Nevertheless, the only study aimed at clinical verification of these encouraging experimental observations provided disappointing results.…”

Section: Nomentioning

confidence: 99%

Enjoy your heart-beets. The role of dietary inorganic nitrate in cardiovascular health

Beresewicz

Gajos-Draus

2016

Kardiol Pol

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Inorganic nitrite stimulates pancreatic islet blood flow and insulin secretion

Cited by 81 publications

References 34 publications

Acute regulation of pancreatic islet microcirculation and glycaemia by telmisartan and ramipril: discordant effects between normal and Type 2 diabetic rats

Acute regulation of pancreatic islet microcirculation and glycaemia by telmisartan and ramipril: discordant effects between normal and Type 2 diabetic rats

Insulin Receptor Substrate-2 (Irs2) in Endothelial Cells Plays a Crucial Role in Insulin Secretion

Enjoy your heart-beets. The role of dietary inorganic nitrate in cardiovascular health

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