Amylin given by central or peripheral routes decreases gastric emptying and intestinal transit in the rat

Clementi, Giuseppe; Caruso, A.; Cutuli, V. M. C.; Bernardis, E. De; Prato, A.; Amico‐Roxas, M.

doi:10.1007/bf01925572

Cited by 55 publications

(47 citation statements)

References 12 publications

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“…In experimental models of diabetes the were very similar to those previously described in the rat brain [22,23]. Thus far, the receptors for calcitonin [28], ratio of amylin to insulin mRNA expressed in the -adrenomedullin [29] and two putative CGRP receptors ing [50][51][52] and the regulation of food intake [53][54][55], which may be functionally related [56]. Amylin has also [30,31] have been cloned.…”

Section: Components Of the Amylin System (As)supporting

confidence: 59%

Interaction of the Renal Amylin and Renin-Angiotensin Systems in Animal Models of Diabetes and Hypertension

Wookey

Cao²,

Cooper

1998

Mineral Electrolyte Metab

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The range of known actions of amylin are reviewed together with the proposal that an important role for amylin may be the hormonal integration of diverse physiological systems activated with feeding. Major targets for the action of amylin are found within the kidney. Components of the amylin system (AS) have been shown to influence the activity of components of the renin-angiotensin system (RAS), and vice versa, in normal, hypertensive and diabetic models. For instance, amylin injected into humans and rats elicits a rapid rise in plasma renin activity. Furthermore, in two models of hypertension (the spontaneously hypertensive rat (SHR) and the model with subtotal nephrectomy (STNx)), the density of amylin-binding sites in the renal cortex associated with the proximal tubules, was associated with elevation of blood pressure. In normotensive controls and in the STNx model, but not in the SHR model, treatment with angiotensin-converting enzyme (ACE) inhibitors reduced blood pressure and the density of amylin binding in the renal cortex. In Sprague-Dawley rats, angiotensin II (Ang II) infusion was associated with increased density of amylin-binding sites as well as elevated blood pressure. Thus, there appears to be a direct relationship between the activity of Ang II and the binding sites for amylin in the renal cortex. From these studies it has been postulated that the activation of the AS in the kidney may play a role in the genesis and/or development of hypertension in certain contexts. The transient expression of amylin mRNA has been detected perinatally, using in situ hybridization, in the subnephrogenic zone of the metanephros and is associated with proximal tubules of the developing nephron. These cells situated close to the glomeruli, represent a subset of brush border epithelial cells. Amylin immunoreactivity (IR) is also found in these cells and colocalizes with angiotensinogen IR. Thus a second important role for amylin is described in which it plays a role as a growth factor in the developing kidney and in renal regrowth in the adult kidney. In a model of IDDM (streptozotocin diabetes), amylin and angiotensinogen IR are both restricted to a subset of brush border epithelial cells close to glomeruli which, in the developing kidney, expressed amylin mRNA. Thus in this IDDM model, we hypothesize that amylin mRNA transcription which is normally downregulated in the adult, is upregulated in this subset of these brush border epithelial cells, and that it stimulates the activity of a local RAS by an intracellular mechanism, leading to the biosynthesis of Ang II. It remains to be determined that if amylin is playing a role in stimulating local Ang II production at these sites, this provides a mechanism for activation of TGF-β, ultimately leading to interstitial fibrosis.

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Section: Components Of the Amylin System (As)supporting

confidence: 59%

Interaction of the Renal Amylin and Renin-Angiotensin Systems in Animal Models of Diabetes and Hypertension

Wookey

Cao²,

Cooper

1998

Mineral Electrolyte Metab

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“…Amylin has also been detected in gut endocrine cells (35), visceral sensory neurons (36), and throughout the brain (44). Exogenous amylin potently reduces food intake (1,3,39), body weight (1), adiposity (41), gastric emptying (10,39), and gastric acid secretion (15) when administered systemically or into the brain. We recently demonstrated that the minimal effective intravenous dose for amylin-induced inhibition of food intake and gastric emptying in rats (1 pmol ⅐ kg Ϫ1 ⅐ min Ϫ1 ) increases plasma amylin by an amount comparable to that produced by a meal (3,39).…”

mentioning

confidence: 99%

“…Several lines of evidence suggest that these peptides may act directly within the brain. 1) Central nervous system (CNS) administration of sCT (13,20), amylin (1,5,10,41), CGRP (20,22,38), and ADM (30) appears to be more potent than systemic administration in reducing food intake and gastric emptying. 2) Subdiaphragmatic vagotomy does not attenuate anorexic responses to sCT (34) and amylin (25,26).…”

mentioning

confidence: 99%

Effects of amylin-related peptides on food intake, meal patterns, and gastric emptying in rats

Reidelberger

Kelsey

Heimann

2002

American Journal of Physiology-Regulatory, Integrative and Comp

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Heimann. Effects of amylin-related peptides on food intake, meal patterns, and gastric emptying in rats. Am J Physiol Regulatory Integrative Comp Physiol 282: R1395-R1404, 2002. First published January 17, 2002 10.1152/ajpregu.00597. 2001.-We previously demonstrated that amylin inhibits food intake and gastric emptying in rats with half-maximal effective doses (ED 50s) of 8 and 3 pmol ⅐ kg Ϫ1 ⅐ min Ϫ1 and maximal inhibitions of 78 and 60%, respectively. In this study of identical design, rats received intravenous infusions of salmon calcitonin (sCT), rat calcitonin (rCT), rat calcitonin gene-related peptide (rCGRP), and rat adrenomedullin (rADM) for 3 h at dark onset, and food intake was measured for 17 h or for 15 min and gastric emptying of saline was measured during the final 5 min. sCT, rCGRP, and rADM inhibited food intake with estimated ED50s of 0.5, 26, and 35 pmol ⅐ kg Ϫ1 ⅐ min Ϫ1 and maximal inhibitions of 88, 90, and 49%, respectively. rCT was not effective at doses up to 100 pmol ⅐ kg Ϫ1 ⅐ min Ϫ1 . sCT, rCGRP, rADM, and rCT inhibited gastric emptying with ED50s of 1, 130, 160, and 730 pmol ⅐ kg Ϫ1 ⅐ min Ϫ1 and maximal inhibitions of 60, 66, 60, and 33%, respectively. These results suggest that amylin and sCT may act by a common mechanism to decrease food intake, which includes inhibition of gastric emptying.calcitonin; calcitonin gene-related peptide; adrenomedullin; anorexia; potency AMYLIN (ALSO CALLED ISLET amyloid polypeptide) is a 37-amino acid peptide that is cosecreted with insulin from the pancreas in response to a meal (11, 51). Amylin has also been detected in gut endocrine cells (35), visceral sensory neurons (36), and throughout the brain (44). Exogenous amylin potently reduces food intake (1, 3, 39), body weight (1), adiposity (41), gastric emptying (10, 39), and gastric acid secretion (15) when administered systemically or into the brain. We recently demonstrated that the minimal effective intravenous dose for amylin-induced inhibition of food intake and gastric emptying in rats (1 pmol ⅐ kg Ϫ1 ⅐ min Ϫ1 ) increases plasma amylin by an amount comparable to that produced by a meal (3,39). We also demonstrated that in suppressing feeding and gastric emptying, amylin is at least as potent and efficacious as CCK (39), a physiological inhibitor of food intake and gastric emptying.These results support the hypothesis that amylin acts as a hormonal signal to the brain to inhibit gastric emptying and food intake and that amylin produces satiety, in part, through inhibition of gastric emptying.Calcitonin gene-related peptide (CGRP), calcitonin (CT), and adrenomedullin (ADM), together with amylin, form a family of structurally related peptides with overlapping biological actions (Fig. 1). Each of these peptides inhibits food intake (13,22,32,45) and gastric emptying (8,20,30,38) when administered systemically or into the brain. The teleost peptide salmon CT (sCT) appears to be significantly more potent than either amylin (29) or mammalian CTs (8, 29, 47) in decreasing food intake and gastric emp...

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“…Amylin is known to be a potent inhibitor of gastric motility (Young et al, 1996a), an eect that is probably mediated by a central mechanism (Clementi et al, 1996) involving the vagus nerve since subdiaphragmatic vagotomy destroys the response to amylin (Jodka et al, 1996). Thus considering that enhanced gastric motility is an important factor in the pathogenesis of indomethacin and not in EtOH-induced gastric lesions (Takeuchi et al, 1994) and that NEM treatment was shown to decrease gastric motility (Takeuchi et al, 1991) such an eect could also account for the more pronounced protective eect of amylin on indomethacininduced ulcers when the peptide was administered in rats treated with NEM.…”

Section: Discussionmentioning

confidence: 99%

Investigation on the mechanisms involved in the central protective effect of amylin on gastric ulcers in rats

Guidobono

Pagani

Ticozzi

et al. 1998

British J Pharmacology

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1 The mechanisms involved in the protective eect of amylin (administered into the brain ventricle, i.c.v.) on gastric ulcers induced by the oral administration of ethanol 50% (EtOH, 1 ml/rat) or indomethacin (indomethacin, 20 mg kg 71 , at a dosing volume of 5 ml) were investigated in rats. 2 The possible involvement of endogenous nitric oxide (NO) in the bene®cial eect of amylin against EtOH-induced ulcers was examined. The inhibitor of NO-synthesis, N G -nitro-L-arginine methyl ester (L-NAME, 70 mg kg 71 , s.c.) was injected 30 min before amylin (2.2 mg/rat, i.c.v.) followed by EtOH after a further 30 min. Rats were sacri®ed 1 h after EtOH. L-NAME completely removed the protective eect of amylin. 3 The interaction between amylin and gastric nonprotein sulfhydryl groups was studied. The rats were treated with N-ethyl-maleimide (NEM, 25 mg kg 71 , s.c.) 30 min before amylin (2.2 mg/rat, i.c.v.) followed by EtOH 30 min after or by indomethacin 5 min after amylin. Rats were sacri®ed 1 h or 6 h respectively after EtOH or indomethacin. NEM counteracted the protective eect of amylin against EtOH-induced ulcers but not against those provoked by indomethacin. 4 To determine whether amylin was able to promote ulcer healing, the peptide was injected 5 min after EtOH or 1 h after indomethacin. In the case of EtOH, the bene®cial eect of amylin was lost whereas it was still eective on indomethacin-induced ulcers. 5 The results indicate that: the mechanisms involved in the antiulcer eects of amylin are dierent in these two types of gastric lesions probably because of the dierent etiopathology of various types of ulcers. Endogenous NO and nonprotein sulfhydryl groups are involved in the mucosal protective eects of amylin on EtOH and not on indomethacin-induced ulcers. Furthermore the eectiveness of amylin against indomethacin-induced lesions when administered after the ulcerogenic process has started suggests that amylin is involved not only in the protection but also in the healing mechanisms in this type of ulcer.

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Amylin given by central or peripheral routes decreases gastric emptying and intestinal transit in the rat

Cited by 55 publications

References 12 publications

Interaction of the Renal Amylin and Renin-Angiotensin Systems in Animal Models of Diabetes and Hypertension

Interaction of the Renal Amylin and Renin-Angiotensin Systems in Animal Models of Diabetes and Hypertension

Effects of amylin-related peptides on food intake, meal patterns, and gastric emptying in rats

Investigation on the mechanisms involved in the central protective effect of amylin on gastric ulcers in rats

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