Atrial natriuretic factor has a weak insulinotropic action in the isolated perfused rat pancreas

Fehmann, Hans-Christoph; Noll, Bernd; Göke, Rüdiger; Göke, Burkhard; Trautmann, Michael E.; Arnold, R.

doi:10.1007/bf00000030

Cited by 12 publications

(8 citation statements)

References 17 publications

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“…36 Therefore, although studies do not exist in humans, it is probable that in vivo elevation of plasma insulin levels in response to ANP are an indirect rather than a direct effect and represent a minor contribution to the lipid mobilizing responses reported in the present study.…”

Section: International Journal Of Obesitymentioning

confidence: 68%

Increased lipolysis in adipose tissue and lipid mobilization to natriuretic peptides during low-calorie diet in obese women

et al. 2002

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OBJECTIVE:We recently demonstrated that natriuretic peptides (NP) are involved in a pathway inducing lipolysis in human adipose tissue. Atrial NP (ANP) and brain NP (BNP) operate via a cGMP-dependent pathway which does not involve phosphodiesterase-3B inhibition or cAMP. The study was performed to evaluate the effect of ANP on lipid mobilization in obese women and secondly to examine the possible effect of a low-calorie diet (LCD) on the lipolytic response of subcutaneous abdominal fat cells to NP and on the lipid mobilization induced by ANP infusion (1 mg=m 2 min for 60 min). SUBJECTS: Ten obese women from 40.5 AE 3.4 y old were selected for this study. Their body weight was 96.4 AE 5.7 kg and their BMI was 35.3 AE 1.7 kg=m 2 . They received a 2.5 -2.9 MJ=day formula diet for 28 days. DESIGN: Before and during the LCD, an adipose tissue biospy was performed for in vitro studies and, moreover, ANP was perfused i.v. to evaluate its lipid mobilizing action in toto and in situ in subcutaneous abdominal adipose tissue (SCAAT) using microdialysis. RESULTS: The lipolytic effects of isoproterenol, ANP, BNP and bromo-cGMP (an analogue of cGMP) on fat cells increased by about 80 -100% during LCD. The lipid mobilization during i.v. ANP infusion, assessed by plasma non-esterified fatty acids (NEFA) increase was enhanced during the LCD. However, during LCD, ANP infusion induced a biphasic effect on glycerol concentration in plasma and interstitial fluid of SCAAT; a significant increase was observed in glycerol levels during the first 30 min infusion period, followed by a steady decrease. The concentration of glycerol was lower during the post-infusion period than during the baseline period. This effect was stronger in obese subjects submitted to the LCD with a low-carbohydrate composition. Other plasma parameters were weakly increased (noradrenaline) or not modified (insulin, glucose) by ANP infusion and no difference was found before and during LCD treatment.CONCLUSION: The present study shows that NP are powerful lipolytic agents in subcutaneous fat cells and that both isoproterenol-and NP-induced lipolysis increase during LCD, in obese women. These changes seem to be associated with an improvement of the lipolytic pathway at a post-receptor level. Moreover, i.v. administration of ANP induced a lipid mobilizing effect which was enhanced by a LCD in these objects.

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Section: International Journal Of Obesitymentioning

confidence: 68%

Increased lipolysis in adipose tissue and lipid mobilization to natriuretic peptides during low-calorie diet in obese women

et al. 2002

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“…In contrast, the studies of the effect of ANP on insulin secretion have yielded discordant data. ANP has been shown to increase plasma insulin in humans (14) and GSIS in isolated rat islets (15). However, in other studies with rats, insulin secretion ex vivo did not change in response to ANP (17) or was even decreased after iv injection of the peptide (16).…”

Section: Figmentioning

confidence: 97%

“…A possible insulinotropic action for ANP/GC-A is still a matter of controversy. It was demonstrated that ANP elicits an increase in circulating insulin in humans (14) and stimulates insulin secretion in rats (15), whereas in other studies, ANP produced no significant insulinotropic action or even inhibited glucose-stimulated insulin secretion (GSIS) (13,16,17). Cyclic GMP, the second messenger produced by the activation of GC-A by ANP, blocks K ATP channels and enhances glucose-induced calcium signaling in mouse ␤-cells (18).…”

mentioning

confidence: 98%

The Atrial Natriuretic Peptide and Guanylyl Cyclase-A System Modulates Pancreatic β-Cell Function

et al. 2010

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Atrial natriuretic peptide (ANP) and its guanylyl cyclase-A (GC-A) receptor are being involved in metabolism, although their role in the endocrine pancreas is still greatly unknown. The aim of this work is to study a possible role for the ANP/GC-A system in modulating pancreatic beta-cell function. The results presented here show a direct effect of the GC-A receptor in regulating glucose-stimulated insulin secretion (GSIS) and beta-cell mass. GC-A activation by its natural ligand, ANP, rapidly blocked ATP-dependent potassium (K(ATP)) channel activity, increased glucose-elicited Ca(2+) signals, and enhanced GSIS in islets of Langerhans. The effect in GSIS was inhibited in islets from GC-A knockout (KO) mice. Pancreatic islets from GC-A KO mice responded to increasing glucose concentrations with enhanced insulin secretion compared with wild type (WT). Remarkably, islets from GC-A KO mice were smaller, presented lower beta-cell mass and decreased insulin content. However, glucose-induced Ca(2+) response was more vigorous in GC-A KO islets, and basal K(ATP) channel activity in GC-A KO beta-cells was greatly diminished compared with WT. When protein levels of the two K(ATP) channel constitutive subunits sulfonylurea receptor 1 and Inward rectifier potassium channel 6.2 were measured, both were diminished in GC-A KO islets. These alterations on beta-cell function were not associated with disruption of glucose tolerance or insulin sensitivity in vivo. Glucose and insulin tolerance tests were similar in WT and GC-A KO mice. Our data suggest that the ANP/GC-A system may have a modulating effect on beta-cell function.

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“…Isolated human islets (80-90% purity) were perifused with medium supplemented with agents shown by brackets and glucagon secretion was measured every 1 min. Data are representative of four experiments in vivo in humans and in isolated perfused rat pancreas (Fehmann et al 1990;Uehlinger et al 1986). However in other studies ANP was found to have no eVect or inhibited glucose-stimulated insulin release in rodents (Ahren 1988;Lee and Laychock 1997;Verspohl and Ammon 1989).…”

Section: Discussionmentioning

confidence: 94%

“…Atrial natriuretic peptide potentiates glucose-stimulated insulin release both in vivo in humans and from perfused rat pancreas, suggesting that ANP receptors are expressed in human and rodent endocrine pancreas (Fehmann et al 1990;Uehlinger et al 1986). Furthermore, ANP binding as well as cGMP production were demonstrated in rat pancreatic islets and the RINm5F cells (Verspohl and Ammon 1989;Verspohl et al 1988).…”

Section: Introductionmentioning

confidence: 96%

C-type natriuretic peptide receptor expression in pancreatic alpha cells

Burgess

Moore

Alli

et al. 2009

Histochem Cell Biol

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Atrial natriuretic peptide (ANP), brain type natriuretic peptide (BNP) and C-type natriuretic peptide (CNP) comprise a family of natriuretic peptides that mediate their biological effects through three natriuretic peptide receptor subtypes, NPR-A (ANP, BNP), NPR-B (CNP) and NPR-C (ANP, BNP, CNP). Several reports have provided evidence for the expression of ANP and specific binding sites for ANP in the pancreas. The purpose of this study was to identify the ANP receptor subtype and to localize its expression to a specific cell type in the human pancreas. NPR-C immunoreactivity, but neither ANP nor NPR-A, was detected in human islets by immunofluorescent staining. No immunostaining was observed in the exocrine pancreas or ductal structures. Double-staining revealed that NPR-C was expressed mainly in the glucagon-containing alpha cells. NPR-C mRNA and protein were detected in isolated human islets by RT-PCR and Western blot analysis, respectively. NPR-C expression was also detected by immunofluorescent staining in glucagonoma but not in insulinoma. ANP, as well as BNP and CNP, stimulated glucagon secretion from perifused human islets (1,111 +/- 55% vs. basal [7.3 fmol/min]; P < 0.001). This response was mimicked by cANP(4-23), a selective agonist of NPR-C. In conclusion, the NPR-C receptor is expressed in normal and neoplastic human alpha cells. These findings suggest a role for natriuretic peptides in the regulation of glucagon secretion from human alpha cells.

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Atrial natriuretic factor has a weak insulinotropic action in the isolated perfused rat pancreas

Cited by 12 publications

References 17 publications

Increased lipolysis in adipose tissue and lipid mobilization to natriuretic peptides during low-calorie diet in obese women

Increased lipolysis in adipose tissue and lipid mobilization to natriuretic peptides during low-calorie diet in obese women

The Atrial Natriuretic Peptide and Guanylyl Cyclase-A System Modulates Pancreatic β-Cell Function

C-type natriuretic peptide receptor expression in pancreatic alpha cells

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