Islet amyloidosis (IA) is the principal lesion in the endocrine pancreas of human beings with non-insulin-dependent diabetes mellitus (NIDDM) and in the similar forms of diabetes mellitus in domestic cats and macaques. As such, the delineation of the pathogenesis of this form of amyloidosis may be crucial to the understanding of the development and progression of NIDDM. Islet amyloid polypeptide (IAPP) is a recently discovered polypeptide that is the principal constituent of IA in human beings, cats, and macaques. IAPP is produced by the pancreatic β-cells and is co-packaged with insulin in the β-cell secretory vesicles. Immunohistochemical and physiologic evidence supports the notion that the β-cells are heterogenous with respect to their relative contents of insulin and IAPP. Therefore, although IAPP is co-secreted with insulin in response to a variety of well-known insulin secretogogues, the molar ratio of these two proteins that is released from the islets may vary, depending upon the glucose concentration and prevailing metabolic milieu. IAPP is highly conserved among mammalian species and has about 45% homology to another neuropeptide, calcitonin gene-related peptide. IAPP is encoded by a single-copy gene located, in the human being, on chromosome 12. IAPP is expressed as a 93 (murine)–89 (human)-amino acid prepropolypeptide that is processed enzymatically, resulting in the removal of amino- and carboxy-terminal propeptide segments. The 20–29 region of the IAPP molecule is most important in the ability of IAPP to form amyloid fibrils. The role of IAPP and IA in the pathogenesis of human NIDDM and similar forms of diabetes mellitus in cats and macaques may involve several possible mechanisms, including 1) direct physical/chemical damage to β-cells, resulting in necrosis and loss of functional islet tissue, 2) biologic activities of IAPP that oppose those of insulin or abnormally suppress insulin secretion, and 3) interference by IA deposits of passage of insulin out of β-cells and/or entrance of glucose and other secretogogues into the islet. The roles of each of these possible mechanisms have yet to be demonstrated. In addition, the physiological significance of the apparent IAPP deficiency in both insulin-dependent diabetes mellitus and NIDDM is currently unknown.
AhrenBMartenssonHNobinA:
Effects of calcitonin gene-related peptide (CGRP) on islet hormone secretion in the pig.
Diabetologia30:
354–359,
1987
2.
AmaraSGJonasVRosenfeldMGOngESEvansRM:
Alternative RNA processing in calcitonin gene expression generates mRNAs encoding different polypeptide products.
Nature298:
240–244,
1982
3.
Ar'RajabAAhrenB:
Effects of amidated rat islet amyloid polypeptide on glucose-stimulated insulin secretion in vivo and in vitro in rats.
Eur J Pharmacol192:
443–445,
1991
4.
AsaiJNakazatoMKangawaKMatsukuraSMatsuoH:
Isolation and sequence determination of rat islet amyloid polypeptide.
Biochem Biophys Res Commun164:
400–405,
1989
5.
AsaiJNakazatoMMiyazatoMKangawaKMatsuoHMatsukuraS:
Regional distribution and molecular forms of rat islet amyloid polypeptide.
Biochem Biophys Res Commun169:
788–795,
1990
6.
BellET:
Hyalinization of the islets of Langerhans in diabetes mellitus.
Diabetes1:
341–344,
1952
7.
BellET:
Hyalinization of the islets of Langerhans in nondiabetic individuals.
Am J Pathol35:
801–805,
1959
8.
BendittEPEriksenN:
Amyloid protein SAA is associated with high density lipoprotein from human serum.
Proc Natl Acad Sci USA74:
4025–4028,
1977
9.
BetsholtzCChristmansonLEngstromURorsmanFJordanKO'BrienTDMurtaughMJohnsonKHWestermarkP:
Structure of cat islet amyloid polypeptide and identification of amino acid residues of potential significance for islet amyloid formation.
Diabetes39:
118–122,
1990
10.
BetsholtzCChristmansonLEngstromURorsmanFSvenssonVJohnsonKHWestermarkP:
Sequence divergence in a specific region of islet amyloid polypeptide (IAPP) explains differences in islet amyloid formation between species.
Fed Eur Biochem Soc Lett251:
261–264,
1989
11.
BetsholzCSvenssonVRorsmanFWestermarkGTWilanderEJohnsonKHWestermarkP:
Islet amyloid polypeptide (IAPP): cDNA cloning and identification of an amyloidogenic region associated with the species-specific occurrence of age-related diabetes mellitus.
Exp Cell Res183:
484–493,
1989
12.
BoyceJTDiBartolaSPChewDJGasperPW:
Familial renal amyloidosis in Abyssinian cats.
Vet Pathol21:
33–38,
1984
13.
BrainSDWimalawansaSMacIntyreIWilliamsTJ:
The demonstration of vasodilator activity of pancreatic amylin amide in the rabbit.
Am J Pathol136:
487–490,
1990
14.
Bretherton-WattDGhateiMABloomSRJamalHFerrierGJMGirgisSILegonS:
Altered islet amyloid polypeptide (amylin) gene expression in rat models of diabetes.
Diabetologia32:
881–883,
1989
15.
Bretherton-WattDGilbeySGGhateiMABeachamJBloomSR:
Failure to establish islet amyloid polypeptide (amylin) as a circulating beta cell inhibiting hormone in man.
Diabetologia33:
115–117,
1990
16.
BrimerLHMacIntyreIZaidiM:
Peptides from the calcitonin genes: molecular genetics, structure and function.
Biochem J255:
377–390,
1988
17.
BuckleVJMarslandAMMosselmanSHoppenerJWM:
Localization of the human islet amyloid polypeptide (IAPP) gene to 12p11.2–p12.3.
Cytogenet Cell Genet51:
972,
1989
18.
ButlerPCChouJCarterWBWangYBuBChangDChangJRizzaRA:
Effects of meal ingestion on plasma amylin concentration in NIDDM and nondiabetic humans.
Diabetes39:
752–756,
1990
19.
ButlerPCKryshakEJRizzaRA:
Mechanism of growth hormone-induced postprandial carbohydrate intolerance in humans.
Am J Physiol260:
E513–E520,
1991
20.
ChanceWTBalasubramaniamAZhangFSWimalawansaSJFischerJE:
Anorexia following the intrahypothalamic administration of amylin.
Brain Res539:
352–354,
1991
21.
ChristmansonLRorsmanFStenmanGWestermarkPBetsholtzC:
The human islet amyloid polypeptide (IAPP) gene: organization, chromosomal localization and functional identification of a promoter region.
Fed Eur Biochem Soc Lett267:
160–166,
1990
22.
ClarkADeKoningEHansenBBodkinNMorrisJF:
Islet amyloid in glucose intolerant and spontaneous diabetic Macaca mulatta monkeys.
In:
Frontiers in Diabetes Research. Lessons from Animal Diabetes III,
ed. ShafrirE,
pp. 502–506.
Smith-Gordon,
Jerusalem,
1990
23.
ClarkAEdwardsCAOstleLRSuttonRRothbardJBMorrisJFTurnerRC:
Localisation of islet amyloid peptide in lipofuscin bodies and secretory granules of human B-cells and in islets of type-2 diabetic subjects.
Cell Tissue Res257:
179–185,
1989
24.
CockburnDHoltSMRobertsANCooperGJSReidKBMBoydY:
Localization of the amylin locus to chromosome 12.
Cytogenet Cell Genet51:
977,
1989
25.
ConnJFajansS:
Symposium on diabetes: influence of adrenal corticosteroids on carbohydrate metabolism in man.
Metabolism5:
114–120,
1956
26.
CooperGJSLeightonBDimitriadisGDParry-BillingsMKowalchukJMGowlandKRothbardJBWillisADReidKBM:
Amylin found in amyloid deposits in human type 2 diabetes mellitus may be a hormone that regulated glycogen metabolism in skeletal muscle.
Proc Natl Acad Sci USA85:
7763–7766,
1988
27.
CooperGJSWillisACClarkATurnerRCSimRBReidKB:
Purification and characterization of a peptide from amyloid-rich pancreases of type 2 diabetic patients.
Proc Natl Acad Sci USA84:
8628–8632,
1987
28.
CornwellGGIIINatvigJBWestermarkPHusbyG:
Senile cardiac amyloid: demonstration of a unique fibril protein in tissue sections.
J Immunol120:
1385–1388,
1978
29.
DattaHKZaidiMWimalawansaSJGhateiMABeachamJLBloomSRMacIntyreI:
In vivo and in vitro effects of amylin and amylin-amide on calcium metabolism in the rat and rabbit.
Biochem Biophys Res Commun162:
876–881,
1989
30.
DefronzoRDeibartDHendlerRFeligPSomanV:
Insulin sensitivity and insulin binding to monocytes in maturity-onset diabetes.
J Clin Invest63:
939–946,
1979
31.
DischeFEWernstedtCWestermarkGTWestermarkPPepysMBRennieJAGilbeySGWatkinsPJ:
Insulin as an amyloid-fibril protein at sites of repeated insulin injections in a diabetic patient.
Diabetologia31:
158–161,
1988
32.
EhrlichJDRatnerJM:
Amyloidosis of the islets of Langerhans: a restudy of islet hyalin in diabetic and nondiabetic individuals.
Am J Pathol38:
49–59,
1961
33.
EisenbarthGS:
Type 1 diabetes mellitus: a chronic autoimmune disease.
N Engl J Med314:
1360–1368,
1986
34.
ErikssonJFranssila-KallunkiAEkstrandASalorantaCWidenESchalinCGroopL:
Early metabolic defects in persons at increased risk for non-insulin-dependent diabetes mellitus.
N Engl J Med321:
337–343,
1989
35.
FehmannHCWeberVGokeRGokeBArnoldR:
Cosecretion of amylin and insulin from isolated rat pancreas.
Fed Eur Biochem Soc Lett262:
279–281,
1990
36.
FelberJPGolayAJequierECurchadBTemlerEDeFronzoRAFerranniniE:
The metabolic consequences of long-term human obesity.
Int J Obes12:
377–389,
1988
37.
FerrierGJMPiersonAMJonesPMBloomSRGirgisSILegonS:
Expression of the rat amylin (IAPP/DAP) gene.
J Mol Endocrinol3:
R1–R4,
1989
38.
FitzgeraldMGMalinsJMO'SullivanDJWallM:
The effect of sex and parity on the incidence of diabetes mellitus.
Q J Med30:
57–70,
1961
39.
FrontoniSChoiSBBanduchDRossettiL:
In vivo insulin resistance induced by amylin primarily through inhibition of insulin-stimulated glycogen synthesis in skeletal muscle.
Diabetes40:
568–573,
1991
40.
GaleazzaMTO'BrienTDJohnsonKHSeyboldVS:
Islet amyloid polypeptide (IAPP) competes for two binding sites of CGRP.
Peptides12:
585–591,
1991
41.
GardinerSMComptonAMKempPABennettTBoseCFoulkesRHughesB:
Antagonistic effect of human α-calcitonin gene-related peptide (8–37) on regional hemodynamic actions of rat islet amyloid polypeptide in conscious Long-Evans rats.
Diabetes40:
948–951,
1991
42.
GhateiMADattaHKZaidiMBretherton-WattDWimalawansaSJMacIntyreIBloomSR:
Amylin and amylin-amide lack an effect on blood glucose and insulin.
J Endocrinol124:
R9–R11,
1990
43.
GilbeySGGhateiMBretherton-WattDZaidiMJonesPMPereraTBeachamJGirgisSBloomSR:
Islet amyloid polypeptide: production by an osteoblast cell line and possible role as a paracrine regulator of osteoclast function in man.
Clin Sci81:
803–808,
1991
44.
GlennerGG:
Amyloid deposits and amyloidosis. The β-fibrilloses.
N Engl J Med302:
1283–1292,
1333–1343,
1980
45.
GlennerGGEanesEDBladenHALinkeRPTermineJD:
Beta-pleated sheet fibrils. A comparison of native amyloid with synthetic protein fibrils.
J Histochem Cytochem22:
1141–1158,
1974
46.
HartterESvobodaTLudvikBSchullerMLellBKuenburgEBrunnbauerMWoloszczukWPragerR:
Basal and stimulated plasma levels of pancreatic amylin indicate its co-secretion with insulin in humans.
Diabetologia34:
52–54,
1991
47.
HellmanUWernstedtCWestermarkPO'BrienTDRathbunWBJohnsonKH:
Amino acid sequence from degu islet amyloid-derived insulin shows unique sequence characteristics.
Biochem Biophys Res Commun169:
571–577,
1990
48.
HothersallJSMuirheadRPWimalawansaS:
The effect of amylin and calcitonin gene-related peptide on insulin-stimulated glucose transport in the diaphragm.
Biochem Biophys Res Commun169:
451–454,
1990
49.
HowardCFJr:
Insular amyloidosis and diabetes mellitus in Macaca nigra.
Diabetes27:
357–364,
1978
50.
HowardCFJrFangT-YVan BuerenA:
Observations on the insular amyloidotic lesion in monkeys.
In:
Frontiers in Diabetes Research. Lessons from Animal Diabetes III,
ed. ShafrirE,
pp. 492–497.
Smith-Gordon,
Jerusalem,
1990
51.
HusbyGArakiSBendittEPBensonMDCohenASFrangioneBGlennerGGNatvigJBWestermarkP:
The 1990 guidelines for nomenclature and classification of amyloid and amyloidosis.
In:
Amyloid and Amyloidosis 1990,
ed. NatvigGBForreOHusbyGHusebekkASkogenBSlettenKWestermarkP,
pp. 7–11.
Kluwer Academic Publishers,
Dordrecht, The Netherlands,
1991
52.
InoueKHisatomiAUmedaFNawataH:
Amylin release from perfused rat pancreas in response to glucose and arginine.
Diabetes Res Clin Pract10:
189–192,
1990
53.
InoueKHisatomiAUmedaFNawataH:
Release of amylin from perfused rat pancreas in response to glucose, arginine, β-hydroxybutyrate, and gliclazide.
Diabetes40:
1005–1009,
1991
54.
JohnsonKHHaydenDWO'BrienTDWestermarkP:
Spontaneous diabetes mellitus-islet amyloid complex in adult cats.
Am J Pathol125:
416–419,
1986
55.
JohnsonKHO'BrienTD:
Amyloid and amyloidosis.
In:
Current Veterinary Therapy XI,
ed. KirkRW,
pp. 59–62.
WB Saunders,
Philadelphia, PA,
1992
56.
JohnsonKHO'BrienTDBetsholtzCWestermarkP:
Islet amyloid, islet-amyloid polypeptide, and diabetes mellitus.
New Engl J Med321:
513–518,
1989
57.
JohnsonKHO'BrienTDHaydenDWJordanKGhobrialHKGMahoneyWCWestermarkP:
Immunolocalization of islet amyloid polypeptide (IAPP) in pancreatic beta cells by means of peroxidase-antiperoxidase (PAP) and protein A-gold techniques.
Am J Pathol130:
1–8,
1988
58.
JohnsonKHO'BrienTDHaydenDWMahoneyWCWernstedtCWestermarkP:
Relationships of islet amyloid polypeptide (IAPP) to spontaneous diabetes in adult cats.
In:
Amyloid and Amyloidosis,
ed. IsobeTTsuburaE,
pp. 673–678.
Plenum,
New York, NY,
1988
59.
JohnsonKHO'BrienTDJordanKWestermarkP:
Impaired glucose tolerance is associated with increased islet amyloid polypeptide (IAPP) immunoreactivity in pancreatic beta cells.
Am J Pathol135:
245–250,
1989
60.
JohnsonKHStevensJB:
Light and electron microscopic studies of islet amyloid in diabetic cats.
Diabetes22:
81–90,
1973
61.
JohnsonKHWestermarkPNilssonGSlettenKO'BrienTDHaydenDW:
Feline insular amyloid: immunohistochemical and immunochemical evidence that the amyloid is insulin-related.
Vet Pathol22:
463–468,
1985
62.
JordanKMurtaughMPO'BrienTDWestermarkPBetsholtzCJohnsonKH:
Canine IAPP cDNA sequence provides important clues regarding diabetogenesis and amyloidogenesis in type 2 diabetes.
Biochem Biophys Res Commun169:
502–508,
1990
63.
KahnSED'AlessioDASchwartzWFujimotoWYEnsinckJWTaborskyGJPorteD:
Evidence of cosecretion of islet amyloid polypeptide and insulin by β-cells.
Diabetes39:
634–638,
1990
64.
KanatsukaAMakinoHOhsawaHTokuyamaYYamaguchiTYoshidaSAdachiM:
Secretion of islet amyloid polypeptide in response to glucose.
Fed Eur Biochem Soc Lett259:
199–201,
1989
65.
KassirAAUpadhyayAKLimTJMoossaAROlefskyJM:
Lack of effect of islet amyloid polypeptide in causing insulin resistance in conscious dogs during euglycemic clamp studies.
Diabetes40:
998–1004,
1991
66.
KiekensRIn'T VeldPMahlerTSchuitFVan de WinkelMPipeleersD:
Differences in glucose recognition by individual rat pancreatic B cells are associated with intercellular differences in glucose-induced biosynthetic activity.
J Clin Invest89:
117–125,
1992
67.
KoopmansSJvan MansfeldADMJanszHSKransHMJRadderJKFrolichMde BoerSKreutterDKAndrewsGCMaassenJA:
Amylin-induced in vivo insulin resistance in conscious rats: the liver is more sensitive to amylin than peripheral tissues.
Diabetologia34:
218–224,
1991
68.
LeffertJDNewgardCBOkamotoHMilburnJLLuskeyKL:
Rat amylin: cloning and tissue-specific expression in pancreatic islet.
Proc Natl Acad Sci USA86:
3127–3130,
1989
69.
LeightonBCooperGJS:
Pancreatic amylin and calcitonin gene-related peptide cause resistance to insulin in skeletal muscle in vitro.
Nature335:
632–635,
1988
70.
LeightonBFootE:
The effects of amylin on carbohydrate metabolism in skeletal muscle in vitro and in vivo.
Biochem J269:
19–23,
1990
71.
LukiniusAWilanderEStridsbergMErikssonBObergK:
Electron-microscopical immunocytochemical study of a pancreatic islet amyloid polypeptidoma.
Endocr Pathol2:
169–175,
1991
72.
LukiniusAWilanderEWestermarkGTEngstromUWestermarkP:
Co-localization of islet amyloid polypeptide and insulin in the B cell secretory granules of the human pancreatic islets.
Diabetologia32:
240–244,
1989
73.
MacIntyreI:
Amylinamide, bone conservation, and pancreatic β-cells.
Lancet2:
1026–1027,
1989
74.
MadsenODNielsenJHMichelsenBWestermarkPBetsholtzCNishiMSteinerDF:
Islet amyloid polypeptide and insulin expression are controlled differently in primary and transformed islet cells.
Mol Endocrinol5:
143–148,
1991
75.
MaloyALLongneckerDSGreenbergER:
The relation of islet amyloid to the clinical type of diabetes.
Hum Pathol12:
917–922,
1981
76.
MitsukawaTTakemuraJAsaiJNakazatoMKangawaKMatsuoHMatsukuraS:
Islet amyloid polypeptide response to glucose, insulin, and somatostatin analogue administration.
Diabetes39:
639–642,
1990
77.
MolinaJMCooperGJSLeightonBOlefskyJM:
Induction of insulin resistance in vivo by amylin and calcitonin gene-related peptide.
Diabetes39:
260–265,
1990
78.
MoriHMoriSSaitohYMoriwakiKIidaSMatsumotoK:
Growth hormone-producing pituitary adenoma with crystal-like amyloid immunohistochemically positive for growth hormone.
Cancer55:
96–102,
1985
79.
MorishitaTYamaguchiAFujitaTChibaT:
Activation of adenylate cyclase by islet amyloid polypeptide with COOH-terminal amide via calcitonin gene-related peptide receptors on rat liver plasma membranes.
Diabetes39:
875–877,
1990
80.
MosselmanSHoppenerJWMde WitLSoellerWLipsCJMJanszHS:
IAPP/amylin gene transcriptional control region: evidence for negative regulation.
Fed Eur Biochem Soc271:
33–36,
1990
81.
MosselmanSHoppenerJWMLipsCJMJanszHS:
The complete islet amyloid polypeptide precursor is encoded by two exons.
Fed Eur Biochem Soc247:
154–158,
1989
82.
MosselmanSHoppenerJWMZandbergJvan MansfeldADMGeurts van KesselAHMLipsCJMJanszHS:
Islet amyloid polypeptide: identification and chromosomal localization of the human gene.
Fed Eur Biochem Soc Lett239:
227–232,
1988
83.
MurphyJCCrowellTPHewesKMFoxJGShalevM:
Spontaneous lesions in the degu.
In:
Symposium of Comparative Pathology of Zoo Animals,
ed. MontaliRJMigakiG,
pp. 437–444.
Smithsonian Institute Press,
Washington, DC,
1979
84.
NagamatsuSCarrollRJGrodskyGMSteinerDF:
Lack of islet amyloid polypeptide regulation of insulin biosynthesis or secretion in normal rat islets.
Diabetes39:
871–874,
1990
85.
NakazatoMAsaiJKangawaKMatsukuraSMatsuoH:
Establishment of radioimmunoassay for human islet amyloid polypeptide and its tissue content and plasma concentration.
Biochem Biophys Res Commun164:
394–399,
1989
86.
NakazatoMAsaiJMiyazatoMMatsukuraSKangawaKMatsuoH:
Isolation and identification of islet amyloid polypeptide in normal human pancreas.
Regul Pep31:
179–186,
1990
87.
NakazatoMMiyazatoMAsaiJMitsukawaTKangawaKMatsuoHMatsukuraS:
Islet amyloid polypeptide, a novel pancreatic peptide, is a circulating hormone secreted under glucose stimulation.
Biochem Biophys Res Commun169:
713–718,
1990
88.
NishiMSankeTSeinoSEddyRLFanY-SByersMGShowsTBBellGISteinerDF:
Human islet amyloid polypeptide gene: complete nucleotide sequence, chromosomal localization, and evolutionary history.
Mol Endocrinol3:
1775–1781,
1989
89.
NishiMSteinerDF:
Cloning of complementary DNAs encoding islet amyloid polypeptide, insulin, and glucagon precursors from a New World rodent, the degu, Octodon degus.
Mol Endocrinol4:
1192–1198,
1990
90.
O'BrienTDHaydenDWJohnsonKHFletcherTF:
Immunohistochemical morphometry of pancreatic endocrine cells in diabetic, normoglycaemic glucose-intolerant and normal cats.
J Comp Pathol96:
357–359,
1986
91.
O'BrienTDHaydenDWJohnsonKHStevensJB:
High dose intravenous glucose tolerance test and serum insulin and glucagon levels in diabetic and non-diabetic cats: relationships to insular amyloidosis.
Vet Pathol22:
250–261,
1985
92.
O'BrienTDHaydenDWO'LearyTPCaywoodDDJohnsonKH:
Canine pancreatic endocrine tumors: immunohistochemical analysis of hormone content and amyloid.
Vet Pathol24:
308–314,
1987
93.
O'BrienTDHellmanUWestermarkPWernstedtCRathbunWBJohnsonKH:
Pancreatic islet amyloid in the degu is derived from insulin.
In:
Amyloid and Amyloidosis 1990,
ed. NatvigJBForreOHusbyGHusebekkASkogenBSlettenKWestermarkP,
pp. 462–465.
Kluwer Academic Publishers,
Dordrecht, The Netherlands,
1991
94.
O'BrienTDJohnsonKHHaydenDW:
Pancreatic ganglioneuronal amyloid. Occurrence in diabetic cats with islet amyloidosis.
Am J Pathol119:
430–435,
1985
95.
O'BrienTDWestermarkPJohnsonKH:
Islet amyloid polypeptide and calcitonin gene-related peptide immunoreactivity in amyloid and tumor cells of canine pancreatic endocrine tumors.
Vet Pathol27:
194–198,
1990
96.
O'BrienTDWestermarkPJohnsonKH:
Islet amyloid polypeptide (IAPP) does not inhibit glucose-stimulated insulin secretion from isolated perfused rat pancreas.
Biochem Biophys Res Commun170:
1223–1228,
1990
97.
O'BrienTDWestermarkPJohnsonKH:
Islet amyloid polypeptide (IAPP) and insulin secretion from isolated perfused pancreas of fed, fasted, glucose-treated and dexamethasone-treated rats.
Diabetes40:
1701–1706,
1991
98.
OgawaAHarrisVMcCorkleSKUngerRHLuskeyKL:
Amylin secretion from the rat pancreas and its selective loss after streptozotocin treatment.
J Clin Invest85:
973–976,
1990
99.
OhsawaHKanatsukeAYamaguchiTMakinoHYoshidaS:
Islet amyloid polypeptide inhibits glucose-stimulated insulin secretion in isolated rat pancreatic islets.
Biochem Biophys Res Commun160:
961–967,
1989
100.
OpieEL:
On the relation of chronic interstitial pancreatitis to the islands of Langerhans and to diabetes mellitus.
J Exp Med5:
397–428,
1900
101.
PalotayJLHowardCFJr:
Insular amyloidosis in spontaneously diabetic nonhuman primates.
Vet Pathol19:
181–192,
1982
102.
PerleyMKipnisDM:
Plasma insulin responses to glucose and tolbutamide of normal weight and obese diabetic and nondiabetic subjects.
Diabetes15:
867–874,
1966
103.
PetterssonMAhrenB:
Failure of islet amyloid polypeptide to inhibit basal and glucose-stimulated insulin secretion in model experiments in mice and rats.
Acta Physiol Scand138:
389–394,
1990
104.
PetterssonMAhrenBBottcherGSundlerF:
Calcitonin gene-related peptide: occurrence in pancreatic islets in the mouse and the rat and inhibition of insulin secretion in the mouse.
Endocrinology119:
865–869,
1986
105.
RahierJGoebbelsRMHenquinJC:
Cellular composition of the human diabetic pancreas.
Diabetologia24:
366–371,
1983
106.
RobertsANLeightonBToddJACockburnDSchofieldPNSuttonRHoltSBoydYDayAJFootEAWillisACReidKBMCooperGJS:
Molecular and functional characterization of amylin, a peptide associated with type 2 diabetes mellitus.
Proc Natl Acad Sci USA86:
9662–9666,
1989
107.
RobertsonRPPorteD:
The glucose receptor. A defective mechanism in diabetes mellitus distinct from the beta adrenergic receptor.
J Clin Invest52:
870–976,
1973
108.
SaadMFKnowlerWCPettittDJNelsonRGMottDMBennettPH:
The natural history of impaired glucose tolerance in the Pima Indians.
N Engl J Med319:
1500–1506,
1988
109.
SaitoKYaginumaNTakahashiT:
Differential volumetry of A, B, and D cells in the pancreatic islets of diabetic and non-diabetic subjects.
Tohoku J Exp Med129:
273–283,
1979
110.
SaitohKMoriHMatsumotoKUshioYHayakawaTMoriSAritaNMogamiH:
Accumulation of amyloid in pituitary adenomas.
Acta Neuropathol68:
87–92,
1985
111.
SankeTBellGISampleCRubensteinAHSteinerDF:
An islet amyloid peptide is derived from an 89-amino acid precursor by proteolytic processing.
J Biol Chem263:
17243–17246,
1988
112.
SankeTHanabusaTNakanoYOkiCOkaiKNishi-muraSKondoMNanjoK:
Plasma islet amyloid polypeptide (amylin) levels and their responses to oral glucose in type 2 (non-insulin-dependent) diabetic patients.
Diabetologia34:
129–132,
1991
113.
SchuitFCIn'T VeldPAPipeleersDG:
Glucose stimulates proinsulin biosynthesis by a dose-dependent recruitment of pancreatic beta cells.
Proc Natl Acad Sci USA85:
3865–3869,
1988
114.
SilvestreRAPeiroEDeganoPMirallesPMarcoJ:
Inhibitory effect of rat amylin on the insulin responses to glucose and arginine in the perfused rat pancreas.
Regul Pept31:
23–31,
1990
115.
SowaRSankeTHirayamaJTabataHFurutaHNishimuraSNanjoK:
Islet amyloid polypeptide amide causes peripheral insulin resistance in vivo in dogs.
Diabetologia33:
118–120,
1990
116.
StorkelSSchneiderH-MMunteferingHHashiwagiS:
Iatrogenic, insulin-dependent, local amyloidosis.
Lab Invest48:
108–111,
1983
117.
TedstoneARENezzerTHughesSJClarkAMatthewsDR:
The effect of islet amyloid polypeptide (amylin) and calcitonin gene-related peptide on glucose removal in the anaesthetized rat and on insulin secretion from rat pancreatic islets in vitro.
Biosci Rep10:
339–345,
1990
118.
ToshimoriHNaritaRNakazatoMAsaiJMitsukawaTKangawaKMatsuoHMatsukuraS:
Islet amyloid polypeptide (IAPP) in the gastrointestinal tract and pancreas of man and rat.
Cell Tissue Res262:
401–406,
1990
119.
ToshimoriHNaritaRNakazatoMAsaiJMitsukawaTKangawaKMatsuoHTakahashiKMatsukuraS:
Islet amyloid polypeptide in insulinoma and in the islets of the pancreas of non-diabetic and diabetic subjects.
Virchows Arch A Pathol Anat Histol418:
411–417,
1991
120.
van JaarsveldBHackengWHLNieuwenhuisMGErkelensDWGeerdinkRALipsCJM:
Islet-amyloid polypeptide in human plasma.
Lancet335:
60,
1990
121.
van MansfeldADMMosselmanSHoppenerJWMZandbergJvan TeeffelenHAAMBaasPDLipsCJMJanszHS:
Islet amyloid polypeptide: structure and upstream sequences of the IAPP gene in rat and man.
Biochim Biophys Acta1087:
235–240,
1990
122.
WajchenbergBLemeCLerarioAToledoTSouzeERodbardHRobardD:
Insulin resistance in Cushing's syndrome.
Diabetes33:
455–459,
1984
123.
WeichselbaumAStanglE:
Zur Kenntnis der feineren Veranderunger des Pankreas bei Diabetes mellitus.
Wien Klin Wochenschr14:
968–972,
1901
124.
WestermarkP:
Quantitative studies of amyloid in the islets of Langerhans.
Upsala J Med Sci77:
91–94,
1972
125.
WestermarkP:
Fine structure of islets of Langerhans in insular amyloidosis.
Virchows Arch A Pathol Pathol Anat359:
1–18,
1973
126.
WestermarkP:
On the nature of the amyloid in human islets of Langerhans.
Histochemistry38:
27–33,
1974
127.
WestermarkP:
Amyloid of human islets of Langerhans. 1. Isolation and some characteristics.
Acta Pathol Microbiol Scand C83:
439–446,
1975
128.
WestermarkP:
The nature of amyloid in islets of Langerhans in old age.
In:
Amyloidosis,
ed. WegeliusOPasternackA,
pp. 533–541.
Academic Press,
New York, NY,
1976
WestermarkPGrimeliusL:
The pancreatic islet cells in insular amyloidosis in human diabetic and non-diabetic adults.
Acta Pathol Microbiol Scand A Pathol81:
291–300,
1973
131.
WestermarkPWernstedtCO'BrienTDHaydenDWJohnsonKH:
Islet amyloid in type 2 human diabetes mellitus and adult diabetic cats is composed of a novel putative polypeptide hormone.
Am J Pathol127:
414–417,
1987
132.
WestermarkPWernstedtCWilanderEHaydenDWO'BrienTDJohnsonKH:
Amyloid fibrils in human insulinoma and islets of Langerhans of the diabetic cat are derived from a neuropeptide-like protein also present in normal islet cells.
Proc Natl Acad Sci USA84:
3881–3885,
1987
133.
WestermarkPWilanderE:
Islet amyloid in type 2 (non-insulin-dependent) diabetes is related to insulin.
Diabetologia24:
342–346,
1983
134.
WestermarkPWilanderEWestermarkGTJohnsonKH:
Islet amyloid polypeptide-like immunoreactivity in the islet B cells of type 2 (non-insulin-dependent) diabetic and non-diabetic individuals.
Diabetologia30:
887–892,
1987
135.
WrightADHillDMLowryCFraserTR:
Mortality in acromegaly.
Q J Med39:
1–13,
1970
136.
YalowRSBersonSA:
Plasma insulin concentrations in nondiabetic and early diabetic subjects. Determination by a new sensitive immuno-assay technic.
Diabetes9:
254–260,
1960
137.
YanoBLHaydenDWJohnsonKH:
Feline insular amyloid: association with diabetes mellitus.
Vet Pathol18:
621–627,
1981
138.
YanoBLHaydenDWJohnsonKH:
Feline insular amyloid: ultrastructural evidence for intracellular formation by nonendocrine cells.
Lab Invest45:
149–156,
1981
139.
YoungDADeemsRODeaconRWMcintoshRHFoleyJE:
Effects of amylin on glucose metabolism and glycogenolysis in vivo and in vitro.
Am J Physiol259:
E457–E461,
1990
140.
ZaidiMDattaHKBevisPJRWimalawansaSJMacIntyreI:
Amylin-amide a new bone-conserving peptide from the pancreas.
Exp Physiol75:
529–536,
1990
141.
ZierathJRAndreassonKGaluskaDEngströmUJohnsonKHBetsholtzCWestermarkPWallberg-HenrikssonH:
Rat islet amyloid polypeptide inhibits insulin-stimulated glucose transport in rat skeletal muscle.
Diabetologia35:
26–31,
1992
