Disease relevance of Iapp

• Effects of amylin and pair feeding (PF) on body weight and metabolic parameters were characterized in diet-induced obesity-prone rats [1].
• Peripherally administered rat amylin (300 mug/kg.d, 22d) reduced food intake and slowed weight gain: approximately 10% (P < 0.05), similar to PF [1].
• Weight loss in amylin and pair-fed rats was accompanied by similar increases arcuate neuropeptide Y mRNA (P < 0.05) [1].
• Congo red also inhibited the pancreatic islet cell toxicity of diabetes-associated amylin, another type of amyloid fibril [2].
• These findings and our previous demonstration that amylin fibrils are toxic suggest that a common cytopathic effect of amyloid fibrils may contribute to the pathogenesis of Alzheimer disease and other amyloidoses [2].

Psychiatry related information on Iapp

• In the present study, the amylin receptor antagonist acetyl-[Asn(30), Tyr(32)] sCT-(8-32) (AC187) was used to assess whether action of endogenous amylin is essential for normal satiation to occur [3].
• Moreover, intra-Acb shell amylin reduced motor activity in nondeprived rats tested in the absence of food or water, indicating that the expression of amylin's effects is independent of drive or proximal incentives [4].
• Amylin (5 micrograms/kg or 2.5 micrograms/rat) injected IP at dark onset after 24-h food deprivation elicited an anorectic effect of similar extent in STZ-diabetic and control rats [5].
• Adult male rats were intraperitoneally (i.p.) injected with 1.0 microgram/kg amylin at the beginning of the dark phase in 24 h food deprived or undeprived rats, and a computerized system measured feeding behavior [6].
• Actions of amylin on subfornical organ neurons and on drinking behavior in rats [7].

High impact information on Iapp

• At the end of the 12-h study period, pancreatic RNA was extracted, proinsulin and amylin mRNAs were measured on total RNA, and glucokinase and glucose transporter (GLUT-2) mRNAs were measured on poly(A)+ RNA by dot blot analysis [8].
• Amylin secretion from the rat pancreas and its selective loss after streptozotocin treatment [9].
• Treatment with a borderline diabetogenic dose of streptozotocin reduced amylin response without significantly changing the insulin response [9].
• Pharmacology of receptors for calcitonin gene-related peptide and amylin [10].
• In this article, the current status of CGRP receptor classification is reviewed by David Poyner, taking particular account of species differences, and evidence is presented supporting the existence of multiple receptors for CGRP, as well as independent binding sites for amylin [10].

Chemical compound and disease context of Iapp

• A role for IAPP in the regulation of glucose homeostasis and the development of non-insulin-dependent diabetes mellitus has been proposed [11].
• Islet amyloid polypeptide (IAPP) is overexpressed relative to insulin under several experimental conditions relevant to diabetes mellitus, including the immediate phase (7 days) following induction of streptozotocin diabetes [12].
• Urinary DPD excretion, a marker for bone resorption, was similar in untreated and AMY-treated diabetic rats (35.0+/-3.1 vs. 35.1+/-4.4 nmol/mmol creatinine), intermediate in rats treated with INS (49.9+/-2.7), and normalized in diabetic rats treated with both agents (58.8+/-8.9 vs. 63.2+/-4.5 in CONT) [13].
• Three electrophilic amide analogues of (S)-2,3-diaminopropionic acid (1, DAP) have been prepared as potential inhibitors of L-asparagine synthetase (ASase, from Novikoff hepatoma, EC 6.3.5.4) [14].
• To reconcile reports of glucagon inhibition with the absence of effect in the experiments just described, anesthetized rats coinfused with rat amylin or with saline were exposed sequentially to intravenous L-arginine (during a euglycemic clamp) and then to hypoglycemia [15].

Biological context of Iapp

• Antiobesity Effects of the {beta}-Cell Hormone Amylin in Diet-Induced Obese Rats: Effects on Food Intake, Body Weight, Composition, Energy Expenditure, and Gene Expression [1].
• In a rodent model of obesity, amylin reduced body weight and body fat, with relative preservation of lean tissue, through anorexigenic and specific metabolic effects [1].
• Energy expenditure (EE mean +/- se) tended to be reduced by PF (5.67 +/- 0.1 kcal/h.kg) and maintained by amylin (5.86 +/- 0.1 kcal/h.kg) relative to VEH (5.77 +/- 0.0 kcal/h.kg) [1].
• Differences in EE, attributed to differences in lean mass, argued against specific amylin-induced thermogenesis [1].
• We have isolated cDNA clones corresponding to the rat amylin precursor from an islet cDNA library and we show that this peptide is encoded in a 0.9-kilobase mRNA that is translated to yield a 93-amino acid precursor [16].

Anatomical context of Iapp

• RNA hybridization studies show that amylin mRNA is abundant in the islets of Langerhans but is not present in the brain or seven other tissues examined [16].
• Amylin is postulated to act as a hormonal signal from the pancreas to the brain to inhibit food intake and regulate energy reserves [3].
• GSK3 involvement in amylin signaling in isolated rat soleus muscle [17].
• In this study, we used the pancreatic beta cell line, INS-1, to evaluate the regulation of amylin gene expression [18].
• Peripherally injected amylin potently inhibits feeding by acting on the area postrema (AP), a circumventricular organ lacking a functional blood-brain barrier [19].

Associations of Iapp with chemical compounds

• However, amylin decreased insulin-stimulated glucose transport by about 30% [17].
• IBMX-induced amylin promoter activity was inhibited by mutations in the FLAT and CAAT elements [18].
• In addition, IAPP-like immunoreactivity occurred in nerve cell bodies storing substance P and pituitary adenylate cyclase-activating polypeptide [11].
• The release of amylin from the perfused pancreases in response to glucose and arginine paralleled that of insulin in all three groups [20].
• Titration of immunohistochemical staining revealed the highest levels of IAPP in the dexamethasone- and glucose-treated groups, followed by the fed controls; the least amount was observed in the fasted group [21].

Physical interactions of Iapp

• The Isl-1 gene in rat codes for a protein that binds to the insulin gene enhancer and is also involved in regulation of amylin and proglucagon genes [22].

Regulatory relationships of Iapp

• These results indicate that amylin is positively regulated by cAMP and PKA through the transcription factors HNF-1 and NFY [18].
• Our data suggest that alterations in UCP2 and PPARgamma2 play a role in the control of insulin and amylin release from the pancreas [23].
• Pretreatment with Indo did not significantly increase the ulcer index induced by EtOH but counteracted the ability of amylin to prevent the ulcer formation [24].
• Peripheral amylin activates circumventricular organs expressing calcitonin receptor a/b subtypes and receptor-activity modifying proteins in the rat [25].
• After acute administration, amylin and its agonist salmon calcitonin (sCT) equally reduced food intake in Zucker and lean control rats while cholecystokinin's (CCK) anorectic effect was weaker in the Zucker rats [26].

Other interactions of Iapp

• The main protein constituent of these deposits is a 37-amino acid peptide known as amylin that resembles calcitonin gene-related peptide, a neuropeptide [16].
• Amylin gene expression mediated by cAMP/PKA and transcription factors HNF-1 and NFY [18].
• Calcitonin, alpha- and beta-calcitonin gene-related peptides, amylin, and adrenomedullin belong to a unique group of peptide hormones important for homeostasis maintenance [27].
• Our current study also explored the relationship between the expression of CTR isoforms and amylin binding sites [28].
• 4. DC-41-33 only partially blocks potent amylin and adrenomedullin-induced inhibition of gastric acid secretion, therefore suggesting that somatostatin may not function as a primary mediator in the action of these peptides [29].

Analytical, diagnostic and therapeutic context of Iapp

• Non-food-deprived rats received a 3- to 4-h intravenous infusion of AC187 (60-2,000 pmol.kg(-1).min(-1)), either alone or coadministered with a 3-h intravenous infusion of amylin (2.5 or 5 pmol.kg(-1).min(-1)) or a 2-h intragastric infusion of an elemental liquid diet (4 kcal/h) [3].
• Electrophoretic mobility shift assays (EMSA) demonstrated that IBMX induced protein-DNA binding to the FLAT and CAAT elements of the amylin promoter [18].
• Isolation and sequence determination of rat islet amyloid polypeptide [30].
• Amylin, a peptide copackaged with insulin in beta-cell granules, was measured in the effluent of the perfused rat pancreases by means of a newly developed specific radioimmunoassay [9].
• In the present study, using in situ hybridization, immunocytochemistry, and immunochemistry, the expression of IAPP in sensory neurons in the rat was investigated [11].

References