B-cell deterioration - prospects for reversal or prevention Diane T. Finegood and Brian G. Topp eyo ls. 2F IC model ogre “The kay cla that reall Anton plays In the pao seein af type 2 dlabses ie becoming incsingly ‘Spparnt Ice now wll entbished that impement of Beall fiction, which becomes most evidest during {nnn essence dt ntented mands for ali, fa ifr fcr Indencing the progesion om ‘ormel luce olen, tough impaled glacse folrance (GTI o funk type 2 diabetes (I Inced there ie sto carlton between the depres of lasing hypeiglyenmin andthe etat ofall dtane ‘don [apd snverl groupe have Kantied aly Avice in Beall fnclon tht are mised 10 the evelopment and progression of type 2 dabetr (34 ‘Thetfo,a greornowndg ofthe undeiying caer ‘of lll dshinction i wl to furharig cut unde. ‘andlag and managumeat oft disease procs. In this erp «nub of ques remain tobe anevered. Foreampl, what omc do ve moan by the tra fall finetin? Is the dyefnction tht leads to & ‘eduction nina seein ln ype 2 dab 0 ‘reall eduction In ol mas. ot progresie ‘ysunction of indigo lls ~ or baht Moreover, vba pact dee prevaing isin reanee have ot {he atnsment of al unto? ‘dually, maasre of Pell aneton should be bse onthe amount of tala leased fr the pences in response to ap appropiate stimulus. Tota isin fainee i « incon of the number of finetonl 8 fale and the args fvulis secretion pa call These factor, however czanot be determined diely in oman al as can oly bo messred rom cedar ance nd ievltng pasa aula nat eet eau of Inalin zecrtion, bcnuneepproxnatly 50% of soc inv cated by Bit pa nthe lve [eb Avs ut various ines a employed a rr serogae muers of Bell funclon in vo. Those Indices are bth epic sucha te asng pes. {nnlin or pasta lave, end physiology based sche the omwowtts mods atatament (HOMA} {nex ol ea function Ia. In th cpans four serch, wo have deed a sis mathemati models, which wo have nd anlyoe he to anal expaiments inorder to gain sight {nt events ozring st the level the panes. Those ‘ode povte importa nfermatin out he Bu of ‘hepeal popltion, which we now knows conaantiy hanging thrmughout Mf [al Signicenly, our teenth in eimal del as shows hat bth nai tent of Pcl function end ls of fall mass ean be prevented by sminisuaton af pacsiome proifontn: elated ector gunna (PPARY agit oor os nt of dnb Those guns ma ot det} 0 te Dore nd india. vis hie fet of improving {reli esi J9.0) The Sige my be bell when cosieing pretent-dyclinia nnd. ‘The rolationship between feel function and Insulin resistence feel fenton and nel resistance ao inextricably Tinks. Baring the erly devslopmont of ala resi tone, isla wleace by the eels ke inernsed 10 omponste for the reduction in inslin sone Wer thie reonship becomes darted rig he evelopnent ype 2 ete. nth ance 4880 longer comport for ineesn in nln rests B eel nein eateries 32.2 Bern and colleges ft developed the conopt hat incrser in Solin este must be me Proportional cretes in inlin sven for main: tenance ef somal ico tolerance, through the inodcton othe deporton de, When insula Fond Simon rua Unity. ea Xn Room KAR Burnaby. Bh Colmese ans ro Ta Fe, Thesnnip ben te ‘icinnlnrpneon eo ‘Seta nda sony {Shines ject ‘Shnlpared pose sence od Inches inp dae een edctnn Rg, Eel pucnetlomn ‘Saupe cv lean. sensitivity (S) multiple’ by an Sade of festphae Instn slete In reponce to glocose was above ferrin lvl abjoate ad oral locos tolerance ‘When 8 inslnrlae lloilo, abet ad nid lacne tolrance Kab oto: evtnded this concept by dtrmling ho relative prone of 5, the eat Snslin response te gucoe (AIR) fr @ Inge soup ofthe und bee, nara subject I. ‘These date elecly demoosvte thet normal glucose {olranoe can be oceved in subjcts wih wide range of inate ristnce Furthermore in studies where 5, thd Ae hve been mouse ebjers with pied {Dace tlerenc IGT and ype? diabetes, AIR Fedoced Fig 1} [5-29 studs performed in ‘bie wil GT the product of he mean vals oS tnd Ait was btren the iat nd the 28 eres ‘ eigiallydefoed by Kab ete. 4, Fr sabes ttn ype # abet SIR ws wll below the 5 recente Thean bese rom Fig 1 tat he dope of inalin essence in popltonswei rormal gluco warn. Wat cary dtnguebs tv groups however. the Jevel of Ball inton at = vee lve of fnelin Sensi. wwe, thar is considomble eveap io thelevel of aRgbebenn subjects with ermal poco tolerance, IT nd type 2 dabtes en, foro given vel tf Peal urtion, tbe dagen of sli esisunce tert 504 eum that dtemines gluons talarnee. Thus, ince of pee uncon, such tr AlRg, must be eushed in the content f the prvalling lee of ulin sensi ‘De changes ia Peal mass also compensa for Arenas in ivan sensi? fa std o Pal tress inhuman cadaver panera, Kloppl_ ta ound snducd Dll sce im people with pe 2 dibees WO), Thin uly also demonstrated at Cty por se was suocned with » poner ell ‘mac. When sited by weight the dat coved « o-oo reduction ia Heal mee in sje with ‘ype 2 diabetes, compared wit) soneabete nd ons Studie ashes tbvae mealys and in Pucker Faty (ZF) and Zacher Debtc Fatty (2DF] fas alio show an ssociaton baton absty and an fepended sll pol, while reall mass ix subtn Tilly lower in sbee atic animale an In chose non-diabetic animals [108142 Factor implicated in call dystunction Topestve Pell defunion hasten ober In ‘pomerous clink studies during the wensition of Patients fm nano! gicom leans. through IGT. fo oan type 2 diabetes 11883 To date tres atone hve Boer saily seocited with the lilly thneved nparment in all neon: lusty Upto ad it any. Dens ce tein 3 See 1 201.820527-|Cucotnity pains gic (OL Aa net two les leas Initaly Teds volcan inulin snctin by the foc f rere Homenttitlence a Hower, Cle ass hyperyemmia sca tele mee Hon, chon hyperiemmi as th ve let ‘Grone hypeycenia te an inden of pot sestle contol ands sgl eecited wi he lication in ype dnb Th dln ek of prolonged exporare of tans to ltd aod Sate lv hereon trad ‘eto cencariog the pence, «mer fennel sie ‘eve danonimte th ft of bypaemaie on he fenton of sls NSA7L Sxerent In mt wh Semosoned fof par an ron sed tured inplten of sont psn isla rapes {748 Sir rer ave Sn btined inno ‘as [whe Sducton of croc hyperemia {trough gluco asin aad nese Bewllmerey ryote 1980) Tos opps et Cheoss expntn of Pls to sbormalibgh ea of fives iran import pitopeie fr ia Beal Steen ah potency leaion of ciruting fee fey acids bas tron “dna isk acto othe development f ype 2 liber [5.5 and prevent nthe fry of ese tins, in adipocytes and eatin ther cl, ftp eid con itherb ada an energy outs (xan. or converted to pyerdes(pogenen. In tome Conditions, th ater pribeay ray reat in the ‘ncsriveaccamsltion of ft within thee call [5 hd nial experimen bav shown tat sacha aon can eeut tn substantial les rom the Beal Population, tug apoptani (25455 "The consqunec of st accumulation in Pel bas boas invited nm nial modal frp abies the obete ZDF et in which fe ty acid lvl se prgresaly prt, rin atscation wth the net of hypegesemis [10]. Ths rae i seated ith 3 srk nce in st ieee content. concn fant wth # deterantion In Bell function and the Alevelopme of iabets (S25. Thar bat bs Alomoneed that iste fom obeie 2OP ae have + ‘markedly Hncmased capscty for lipogenesis and Ahacresed capeciy for oxidation, and har been sgn th thi coll aco thigh ak Svsapent fd in th nim Ot wars have shown Unrated spoptosin tne othe (Boss Frat and vest ta let iene curslaon could nal corn ol dea Inrong the FPARY apo oglacoe ae on ‘own oredacthe tienen wltedite from otce ZOF say ove 0% and inprve Beal spon te gluco 2bld [6] This ter the Geshe a erty rapes attract ing for incresng nin sian, set ali aot amyloid post are abrved In p to 89% of paints with type 2 dab, during ptbolegia eaminaton of pancreatic scone Bom avtopey, But ‘a raely eocountred a individuals with poral tutes homes. Tho phosomanon epperst be harcore af ype 2 dla. and Isat ated ‘rth pec subsections of te popslto. I has bon ‘Suga thet Ist amyloid depertuon oes ecy ta ‘heen proces, progress using aedotion Ist mas,» eonsquent Impact in sli see on, and lta theveplacment of als by amyloid éoposts (571. Contiaed scumuation of lt finylold bas been asiciaed with propestive Peal Ayehncian, edction in nl serene la of ‘rll mars [37-50 but the zeal significance ofthe ‘ontrbton ofthis pheoomenon oth tly ype 2 abe east be seid. Beall turnover ‘The all population snot state, bate dtorined by ‘he talane of all proiftion and al! dst 5, a {his epoca tha aperses ought fe Cel mat few. ora rout of Inrses In Doth Bl numbne (hyperplasia and indus! fall sleme Chyprso- hy) Gall denth acct in paral, eulting kv ell tous tht under normal conditions, is eapale of Pell thx can be delied, qe simpy. atthe Aiferesce baoers the rae of new cll formation and ‘he tof call death, Call oration i govered by we [aces ~ the ate of plication of extng cls an the rae of regent of Bala rm pacunr sem cl uch ar ductal call ~ call death occur yaar across of apoptsis J]. Sone af the paraters Invored i eal trove eas be quanti nan ‘dls of pe dab, naling the nthe allC “Tn Poe Pe OO Fe. 2 Thea ni and Gc (BG fede, alpina end aha pede oe a gocorcresaen 0) Thm cinn seen Stab a Cand crs ‘ecenstan Th pss paced up ‘Spade onlod gre sad nan snot population be moniter. Wo have dvived sine ‘ton wit which we can ass nl aan ‘xprimens end deere whether the all pope tion sn sate of et meogenest' of et call death 10) and oe can use theve Bigs fo en agents "hat fe! balance, cell fnetion in insulin resistance and type 2 “Th Zucker abel faty (ZO rt mode! ‘The Z0F mt en enim of cbs and abe ‘which has ben ud extenively oad the develop ‘pent of te 2 dais 3) Decne of he muny ‘inure the bran dae intemal date Aevlops between 7 and 30 wesks of gu afer pro ‘hee nag nein recstanceand bey. The 20F ‘at model is beoeatly ged in compute tudes with ‘heneo-dbtc obs animal the 2 ose 2 model ‘with sper all ompenation and thf ter [Bye cnel and the ZDF loan canola ees zr ‘A recent ady, ueog thie animal mods (2) termined te factors goversing onl x 6] daring ‘howed thet botwean Sand 7 wks of pe. pir othe ‘nut fae, all mao te cb es (2 end {Flt similar bt ppm doublet of the lean oni ZDF]. By 12 week, the real me oubed foe ean cntel ouput Ince ld In the obo non-iabte wails However, the obese sas that deve oped dbs bad 80% er Bl ase ‘thos the sondlabtie state animals. Frberexpe Pos an ments. showed thatthe ma rate of all ection ‘wes sigue gener in ib ormale tani {he nondabte gouge. Th nds tht the rede tin in Pee mass war nu oa reduction ie ll rokeration ut 0 change inthe tlance betwoen ope ed call deh, Materia modelling Teo reve tao et ll death ‘The IG Moda Mathenatial modeling for dibs bas, 10. et primary focused on medeling with» singe variable fempooant panel the lod gluco eine level {1380-8}, een medals creping blood gcoes end fnaalia 1685], We have reanly developed a tre: ‘component mathematical modal tht incorporates ll ‘matin colunton with inulin nd blood glace ke iC mal Jt (Fg 2 me dl we sae he Tn the Beal replicon ‘at and the rte of Ball hath ae Gependes on te eatcetntion of bloed une. Invln sscrton J dependent on Bll eae {nd blood glicre and indi clearance i dependent fn the inane Silat othr mode of cose Ener, bulb glues prediction and upate In ot mode or dependent on Hood gvcoie snd inslis levels The BIG ide! alles ue to investiga the comple ntractone baw fall ms, inlined shure in oral annals wel oa sig nto {he dle. of dle, tha lt inthe development ypericanmi, Since teres vr lilt walled onthe let the bond plucowe love on al ase x (07,50), 8 Psulsed that incesing gucos stimulated Pell replicon and inhibied el dents win he nome Pllogial rnge (ig. 3) Hower a lod gncme love size ito the range we ually sesociae with cas testy, Seal mplialon ban olan fall death bie forse, Tau at low oncestrtins of ‘Docoe, eal veplcton (cave row, and peu fnerees 10 tsch + pe before fling a high onceneaons of glcore. In cont, sll death (carve bhi sigh ek gluco oncentetins, alsa huze eancenttins neon, x thigh Jinies comerinne ae teal hee abviets the cll rpiaton and doth crv cos so ein glocoea eve, diving the fel fox Int hee zone. The St niacin of heel deh ‘bd repletion cari conidered tobe noel ba coe. something, suchas at ncaa in nel Sensi, dives te gucose lee! lower (ne Zane Iypogyeom,he feall det rate becomes grater ‘han he Beall plication ra eligi a edton2a peatrptaton Nora Plasma glucose —> tattoos i. 2 Moding ft i of plana lea cecraon ‘nen apoio ad eth (ie sow soma ‘cert dh nt xd opin zoe tom rs ce eel penton ‘Soma gra ato Zane engl Sinem iegconilomam e ‘Moat Peal emacs rrpetan 3), ‘Senne msde caer Santee fn Beall mas, which dives the glucore Tool back towards norma If something, such as insulin rae {anc lesdeto a increase in plasm glucose abvetasal tate Zone 2; mild hyprgyeumiahe Ball open tion ate bucomas grater than the call dosh as ‘hsn th nll mas oincrae and dee the pcos eval back dws towed normal 1th te a which the psn lacove vel in fate tha th at at wick ‘he all mass can adap the gluco tee wil ‘cntin ore, posaly into Zon 3 (arene hype Hyena) fn Zope 3th ato of Pull danth I pn [Peter an the Bol repinton rate casing the ell, ‘ture fo dacreno acd diving the glease vol to incren ven ftir. ‘hls paadgm sugges 8 navel nerprttion af he cancgt of slacae ‘onc Rather Dan thisking of ‘Saco toss w snply the lfc ofglacae toad Deal death or psc esl plication, lacasetexiety fan be thought fa thew of glocore to eure an ‘mbslance teen el replation and Bel darth. tn igre 2. hoor oly would ocarif the gucooe lavl entered Zone 2. Eventhough, in pate of Zane 2 {incre plan poco ln to adorn ia Beal relition and an lneroue im Ball dasth the igh 1m ogi eats bee 2 te (© Fate ZF 1D rm ee 20 © vee anor i an be og in| os oO] eee 2 name inais® o-Ps ace sgl = SEND ig wr Stet wh onginoor nb = 04 sl aod eg oie mph ei 20 ‘Raed eprint DE cbc Sete Dart) Dood sucose may bn reversible, Uf eulelen te is salable for he el mass aap "Toe IG maclthrfore provider « mans to lst Inypathee oe Dall yafunction ad the patho ums ol ype? ditt, Thamodal can lzobe wed 2 ‘tol to nvrtiats th fico teepetcntervenion Ge thee tee, penmwers Beall Rictn, ple {tuuin and plane glcsee. tmporamlyy the BIC ‘nodal may provide ta bss or the edie! sessment fell mania we “The affect of PPARY agonist nfl Sroetal studios have invited the lle of PPAR) gaits om Pel fnction In animal models of type 2 ‘nite, Sith ea Rave reported the. the abs ‘Uke moare mol the PPARY agonist esigltarone fncrnsn puneretic islet arn ty 50-65% and lt Aheosity 20. The Increase in let denaty was hameterzed by the eppeerance of stall clusters of fall ssning inersely for iguln,ndiative of fehenen oaegeert 60). These eserves suggest ‘hat rrigltaace hus Bell sparing or protective fcton, In aion, chor worar have ablicbd, ka the DF thet elton prevent the detention in ilet morphology ded by salad byperneal- ula [70.7 I oe sad, seinen of rshne Peps mee zone oF rasa 8 weeks get ifr the fonst of hsporlyaonia)prevenod the tension Yo enten and sera Bel ultastctre 7 "perl, or awn stadar in the ZDF rat have ented that not ely devs rosiglazone prove the net of hyperlyeaemie that normaly oscre A710 Weeks of ae ut W als prevents the ecesie Bell Investigated the llc of igtzane onthe hang Sell mare and epiation rte In ZDF Vas nd bse] ommencing at 6 weske of age (OL While ‘noted, obese animals developed sigaicant hype (Dyce at 12 weeks of age, the rerigiazone rete ‘poup remained normelyesmic iy 4 As eps B- ell death thar wa litle change he wea ond rovgarone-veted len rt ding he experianal rad In contrac Bell dosh increased sobetatnly {nthe cbeeunreted animale during th course of tbe study. colacient with the isn Im licone loves. bose rae owever,raigarone reduced set Pall otha hi tc ans to preservation a bef allman fac, ell mae the eal sted with rosiglitazone was lnost twice that of the unectod otal group 16 weak of ee. ‘hsm sumunary ta tho ZDF ania modal of type 2 lsieta, 2 reductlon Bll mass eccursafter tbe easel of ites, due predate an nose ‘herate fll denth, Rosiglitazone however, as bon shown fo mainten Bll mass by decesing Bll font in the ZF rt. Our rstch bar these ihe the potential of ronghtazone to alc 0 undaying causes of type 2 lbetes,nslin reste ‘nd eal dytunetion, and to prevent or poaily reves dese progres, 1 gratefully acknowledge the Bnapcal support of an a rigitne in Zacher disbaic aty rat and al ‘hank te Mathemsts for Inferation, Technology ene CConples Syste Netwatk Cente of Excllens, fo sippring tho work on wathematal modeling References Pathogens of pe 2 date mele Am | oo, S08 Supt 25-6, 1 Mathews DR Ell CA Sra IM, Hn RR, Tre FC. UX Praspactive Dake Study (UKPDS) Croup pe sateanon 3 Pon Df Norns for pula the mee Se syndrine Theale af ea yet, 4 yer Birds Cat DM, Prey RE, The nau rosie the pabopean of tye 2 doer Salts jin nv toe 304 787-70 1 Flt Ese es ofl by lw: Anno Rov Me hithews DR Hovkne J Radaals AS al Iwecll hncion fem fotng plasma locse nd ‘tele canantatins i man: Diba 100: 28 7 Bonners. Perpecive: Ponape cl tponth,Endnsoy 200; 4: 135-020, dl Mol Eoderin! 00m 2297-902 Saal AR, Olly Thisldineione in the Dea 106 a: 1081688 10 Pega Dr McArthur MD. Kovang Deo Beta oe peas thee not el dah Dts 201 2 troninnsedepran) distr ain In ce facdacnnee ce Delage 19; 36-48-40, Progen of DDN. A blanco oar Diao, 3 Baran A Plipe 5, Cabal Paalpl tla on of hts convoling paces tase i man ‘netsrmen fila seat aed Bal pore ati frm the reponse ntwreous luce. J (Queena ef in rstonhip tenses inn rst and sll ftom in bumen moe Evdenes fora ypale funtion Dahl 10935 4 16 Ae SL Foot WY, rns Kaba SE cof ears on eu lar ntact aur the inal moll technique. epenons fr profuc we Bwiowite [Por B Kor Sk ol Bec of ‘togiaroe on nin witty abd pancrtl 17 Brn F Bovis 0. Moana FF to tacos sli {tl reve hypogtvanmie Ala Dal 1956 33 18 Dyene NOM, Ste J. Oa MOA Polanaky KS te Ste18 DAlle DA, Kabs SE Lave CR, Eniock 1. Clcagniike pepe 1 eahoene gc tales beth y imate fea lens by nrg Inninindopndet glocae Sapont | lin vet Uienessi aoonel and orem hyp wes 21 Hebe Cones RE Pyate SR. Nandan, a 28 aetontroem antaoe lolnicdepandnt acess "pan eomal men ln dese Mt 198 6, ‘eta wet of sutton af compan ctchy- Aves fran ts lau wih any a 1 Jason © Raphe F, MeCulcs DK eta, atl Fancton and sli sas to nn-abte HA ‘deme nbloge of foslit-dopendet dibs 1 Kah SE. Bord JC Seer MW oa. ncroidbe celsoroy apa a mechani fr lt adaption 1 let seinen Iai rates, at 2 Kain SE_ Began RN, Sehwas MW, ebay one D. Short bypergieonla and iene fain inptve iar acon but da tthe gucase ‘clos tn noma! uma Am J Phyo 100 26, sues, 26 Kat SE Laea VG, Sehwats RS t,o ting dls thw inpcencs of Beall yao tothe ghcow inisnnce of human ging 7 Cha 27 Kraryeia YT Hay D5, Degman RN, Melton Inula seat. oman scetn nd con aie trons in dete nd aaah ote pats Diabla 196: 312028 2 Keopll M Sins. Wital D, Dron P. tui farina on compen nein rt i mi aged parsons wth hyperemia Ana NY ‘nod Sei ton e250 on ln com branes, Cyt uppreion of Ieain ‘Sen an innate secon ie arma weight ut Bt ‘hs, boc, la Son 742-70, 0 Mekianes Rupes | Pleo DT. Clann Ayan EA A comparace ah efi 9 ft ade fom lined ol td Sei in wasntoied pe labo, Dib Cae 88 1: 2-07 31 Monow UA, hoqunah 3 Haroun WH Bergman RN ater J. ec of enone eo lnlintceon 232 Ou Called, Scheer OF Paths ban ‘sa mp noe tno ype tes ‘a Alcar-Amercans. Tw sense offline ton, isin sms end slurs eBocioere of lucene oeabee Inn Renta Athens Bogurdus C. Deterirsin in exshydrve metabolism ‘nd poprotin changer lon by mate, gh ft eta Pie nn nd Casale, | ln Eoin 235 Tangs A, Nala, Fakusina Mot of Patogae lotr repose fer paces nlc fn patent ‘sd ODOR lan ah 180-1. In wo bggos wibinimpaed pce llr. A ‘isin! mode snl Ds Ye 100-80, 1 Tange A. Natal ¥,Fakubiow Metal ali eosin satan, ed gue tectose Ss ajo wth imped coe trace a cal ‘ol anal Mattie on 3 3-78 38 Ward WK. Jobson Cl, Gard tain rence sd inpaced lala ttn nutes wih bees of anutonal dake malts Caer 888,38 38 Wain, Cb 55, Barun RN Pipe. Mina ‘mol ants of intavenae gc lean ft Side ey dee | Cn 40 Kopel Lae Heh K Obie Mts PU llc pthlogy andthe patogenis ot ype and pe? she mite lS Sth atl Ra 8 41 Konig E- Bodin NL Hansen BE, Cla A. Disha elitr in aces multe mony inch y lt mid and seduction n bt popeluon, 42 Dik A Cat fab Cao Roof poo in Seetanc and btecll delat the mle Zaher 45 UK Propecia Date Str (URPOS) Coup. UK prorpecive bts study 18 Cronin of 8 ar shop oe dite « pps Swe (4 Unger Candy 5 Ropero ander swellaraconmqonscf paid al conse te. alo 8, 8043, 45 Sato IM, Adler AL, Na Ao ol. Aan ofPlone of ype 2 able (UKPDS 81 posecve ‘teat sed Br Md 2000 28 20-41 46 Yrvinn Ht Cloee tly. Eads Re 18: 1 48 Rona [Shulman Gl, Zale W, Deon RA fhe of Gvonie hyperemia en in to Inala section npr pancatatmiaed te Pn 0 Lnhy Tl Coaper HE, Weir OC. Impure isi fecmton wenchted with att normogiemit Sy i poral ie with 38 in bo glace Inne 1 Pantin. Tolan! PA, Foley JE at aA high cscneaton farting pions no-trd ay cds {e's ak her for the derlopment of NIDDM 2 Ln. Hime Obed M fal Btscl lpn Se 5 eaten of sonar de flaonge, Pro el Acad Sel USA 1068 53 Unger RH. How bes cuss dates in Zier Disc Fay rt Tw Endosie Miah 1007: 7. CGpeciy ofthe lls of sate a: tle ine ‘uhopcmsis of MDDS Ditto 207 4848-43. ss Shimabhuro Zhou YT, Lani Unger ety Indeed bs el papi nk baton ses ad nes Prec Ral fend 8 USA So 95 208-02 ‘Troglitazone lowers falta and rates but call funn of Zach dete fey ste J Bil Chom 19 Kabn SE Anropcle 8 Varchre CB. ay Tong rnopnieed tat underpprecid paolo fare of pe 2 dab ite $00; 48 20-283 ss hot A, Wale CA. Bury ID so Mt nyo ‘Staite change ine ance ny 2 abe. iain too: 31208 ‘0 Wesemar P, Winner E. The sfuane of amid eps ha ht hue in matty oat See ae, Dae 178 8; 97-2, os aaron Pingo DI, Seagie L Sonnereir 8 Dynamics of 1 Senge L. Cobill Cl Fingood OT, Bonner 5. ‘Appts parcptr in the rodling ofthe edo fae panei the ona a EBdesaley 087 2 agen RN, ier Quite etimaton of vn sn. 2 Tule Digna Rs Tngod DF, Bowden Cote © Quentiatve timation of total se 1 Stale. lnfnce of aco foul ad fined Invalin'on hepatic pat utp Aan NY Aen Se ‘insula seasitvy in vv. Eador Rev 1985 8: 45-28 66 Topp Polio K, Devs G. Mire HM, Fwgnod DE A moda af bute! mut, inal, and gheoee inw Pahwaye date Thor Bil 200 206° 67 Bleor Zar SV. 2hvtovety Beta Claas end toinenia inden pepo in pancetta A roo dapat on ear Ca” encatton. leh ane 29353-33507. a Hag Sk White MF. Rhode Cnet growth factor 0G) tilted pancreatic bea owe tHocuedependent Syoupte ection of Iain Facpar sae mde gpl naan pa srge by peace snd IGF in IS ele Bal Chen 6 Sri aa D,Breberan Wat Dea Resgtacee Ince penne st rm desi and isin Sm: (Supp 3 72 20 Bucingha RE, Al Bazan! KA, Tenn CD. Peroxtome,prlfirteracvatd rexpar gei ‘ovglitaone. rote spun Pepopty and pa ‘Sat sori Zakari 7 Sm Sa, Liter CA, Toland C, Being RE Rogan proves the one of ypepiyenemi ad fri the Dah Sn tyr. Dbl ‘bey aol 2on 8 93-272 Ya, Rowen GR cabal € Am | ite, tei ad Mai, 3S 120%, S527