L16 endoc panc

Question 1

LO2: desc how ultrastruc of beta cell relates to synth and stor insulin.

Answer 1

• panc- large gl. devs emb as foreg outgrowth. exoc dig enzs sec to duod, maj of func, alk sec to duod by panc duct. endoc horm prod from islets, endoc cells within alv. iselts stain pale.
• endoc panc 5 pp horms- insul, glucag, somatostatin, panc pp, ghrelin. maj cell types in iselts st diff- beta insul, alpha glucag, delta somatotat (regul islet cell sec), F pp (GI func), new cell sec ghrelin.
• islets endoc. small spheric strucs cont 6000 cells scatt in exoc tiss. 1-2% panc weight. 75% beta, 20% alpha. both stor horms intracell in mem lim vesics bef sec, can cont 13000 stor vesics per cell. ultrastruc repres prot synth and export- lot rER, well defined golgi, lot mito, well defined sys microtubules and mfilams.
• insulin 51 aa- 2 chains- a and b. link cov 2 S-S=rigid. 3rd intra S-S in A chain. affs how synth as S-S have to connec corr cys. .
• insulin mRNA transl as 1 chain precurs preproinsulin 109aa. sig pep 23aa (ensures ent ER) rem dur insert to ER= proinsulin (folds to lign for corr bonds)- in golgi endopeptidases excise C pep 31aa and 4 basic aa from mid chain= mat insulin (2 new chains held by S-S) + C pep. both pack in golgi into sec grans accum in cytop. marginat- grans move to cell surf- exocyt on mem fus to rel conts to circ as good vac supp. daily sec 15% tot stored insulin ni panc. short life so no carr. C pep in plasma usef marker endog insulin rel. monit in pt receiving insulin
• insulin stored in beta cell grans as crystalline Zn insulin complex. when rel diss in plasma and circs as free horm.
• glucagon- 1 chain 29 aa. no S-S, flexib struc takes up active conf on bind R. synth by alpha cells as pre pro glucag that is post transl proc to prod active. no cleav req.
• both water sol. diss in plasma. t1/2 5 min to maint tight range quick. interac targ surf Rs. R with horm bound can be internalise- inactiv.

Question 2

LO3: expl roles insulin and glucag in contr metab

Answer 2

-contr insulin sec- keep BG norm range. contr by metabols eg gluc, aa, FA. GIT horm seg gastrin, secretin, CCK. neurots eg adren, na, ach. metab sigs and GIT horm sstim sec. adren and na inhib.
-glucag sec- incr by decr BG conc. inhib by insulni and incr BG.
synth in RER transp to golgi. pack in grans, held cell surf for rel. eff mainly li8v. grans to surf- margiantion is movem stor vesics to surf, exoc is fus vesic mem to PM, rel conts.
-DM- T1 absol defic as beta destr or reldefic- sec resp slow or small. T2 norm or incr sec but resis- defec R numb or affin, defec post recep events, or excess or inapp glucag sec.
diab insipidus kidn unab cons water.
-insulin resis- decr resp. 92% of T2. 25% pop. comb genet and env eg obes, sedent. resis bef 12yo onset hyperg and dev T2 overt. init beta compensate by incr insulin prod, event cant maint=imp tol. finally beat dysfunc= relat insulin defic.
-chronic hyperg- musc decr upt gluc and decr glycogen. adip decr upt gluc and decr lipogen and esterfi. liv decr glycogen adn glycolysis, incr gluconeo.
-LT complics- musc decr upt aa and prot synth. adip decr esterif. liv gluconeo fom musc aa, ketogen from FA. =musc waste, hyperg, ketosis.
-hyperg conseqs-
acute meatb- glycosuria, polyuria, polydip.
chronic microvasc dis- eye dis, nephrop, periph neurop.
macrovasc- CAD, stroke, poor periph circ.

Question 3

LO1: desc actions of insulin and gluc

Answer 3

INSULIN:
-targ tiss- maj liv, skel musc, adip. is req for norm growth and dev. interacs Rs of tyros kinase fam. insulin R dimer- 2 ident su span mem. su made of 1 alpha 1 beta chain. alpha ext mem, beta spans. chains connec by 1 S-S. when insulin binds a chains move togeth and fold arnd insulin (S-S). this moves beta togeth=active tyr kinase. init P casc= incr GLUT4 exp and isert to mem=targ cells upt more gluc.
lowers BG, brain etc not store so need const circ lev. regul narr range. brain uses gluc v fast, relies on blood, sensit to decr BG or incr osmolarity. norm 3.3-6mM. after meal 7-8mM. renal thresh 10mM, above= glucosuria. thresh decr in preg, incr in old. norm filt gluc reabs.
-actions- affs acrb, lip, aa metab. largely anab effs, clear abs nutr from blood. most effs in sec/hr in resp to incr insulin conc, prod by changes in activ pre exist en and transp molecs. has LT effs (hr/d) on cell growth and div related to abil to stim synth new prot and dna replic.
maj acts on metab:
incr gluc transp into adip and skel musc. insert GLUT4 chann.
incr glycogenesis and decr lysis in liv and musc.
decr gluconeogen in liv.
incr glycolysis in liv and adip.
decr lipolysis in adip.
incr lipogen and esterif of FA in liv and adip.
decr ketogen in liv.
incr LPL activ in capill bed of eg adip.
incr aa upt and prot synth in liv, musc, and adip.
decr proteolysis in liv, skel musc, heart musc.
GLUCAGON:
-targ- liver and adip. affs acrb and lip metab. catab.
- maj acts-
incr glycogenolysis and decr genesis in liv.
incr gluconeo in liv.
incr ketogen in liv.
incr lipolysis in adip.
-MOA- bind G prot coup recep= activ adenylate cyclase which incrs cAMP intracell. =activ PKA= P and activ imp enzs.
-RISE IN aa STIMS BOTH- insulin stim prot synth, decr breakd. glucag incr as catab. need both to maint bal.
- effs on lip metab are slower. gluc and aa upt effs v rap.