Introduction Insulin is synthesi,ed in the rioso*es o the rough endo.las*ic reticulu* as a larger .recursor .e.tide called .roinsulin( It is then later on converted into a s*aller .e.tide! insulin in the golgi a..aratus( In .resence o increased glucose concentration in the lood! insulin is secreted y the eta cells o the .ancreas to lo'er the lood glucose level y increasing the .er*eaility o the cell *e*rane to glucose s.eciically y all *uscle cells and adi.ocytes( /his occurs y inding o insulin to the rece.tors on the cell *e*rane 'hich 'ill then trigger the auto.hos.horylation o tyrosine )inase resulting in the ex.ression o *etaolic eects o insulin( hen this ha..ens! the cell *e*rane o *ycocytes and adi.ocytes! eco*es highly .er*eale to glucose y translocation o glucose trans.orter .rotein-4 2+/-4 ro* the cytosol to the cell *e*rane( /he increase in 2+/-4 then increases the trans.ort o glucose into the cell(
5igure 1( $echanis* o action o insulin *yocytes and adi.ocytes
Chhara! 6016 Insulin is also degraded in the liver once it enters the .ortal venous syste* 'hile unextracted insulin enters the syste*ic circulation 'here it inds to rece.tors in target sites( /hat is! the *yocytes and adi.ocytes Chhara! 6016( In the liver! insulin inhiits glucose .roduction! this then! together 'ith the increase in glucose u.ta)e o *yocytes and adi.octyes 'ould lead to decrease in the concentration o .las*a glucose concentration(
5igure 6( 2lucose ho*eostasis *ediated y insulin Chhara! 6016 Ho'ever! in asted state! there is a lo' insulin level( /his then causes decreased glucose u.ta)e y *yocytes and adi.ocytes! *oili,ation o a*ino acids and ree atty acids and increased glucose .roduction o the liver y gluconeogenesis and glycogenolysis( /hese t'o .rocesses are sti*ulated y glucagon! a secretion o the al.ha
.ancreatic cells( 7n the other hand! .ost.randially! there 'ould e an increased glucose concentration 'hich 'ould cause insulin levels to rise and glucagon levels to all( In this ex.eri*ent! the eect o iatrogenic hy.erinsulinis* 'as de*onstrated as 'ell as the co*.arison o the eectiveness o glucose and e.ine.hrine in the treat*ent o insulin-induced hy.oglyce*ia 'as done(
Methods $ice 'ere laeled as #! :! C! and &( /'o *ice should have een asted 64 hours eore the ex.eri*ent( :lood glucose level 'ill e initially *easured using lood collected ro* the tail vein( /he ehavior and res.iratory rate 'ill e oserved( #ter oservation! our units o insulin 'ill e in;ected intra.eritoneally IP into each *ouse( Changes in res.iratory rate and ehavior 'ill e oserved again( /he ti*e o the onset o tre*ors and convulsions 'ill e docu*ented y ta)ing .ictures and
videos( #s soon as the tre*ors and convulsions are oserved! lood glucose level 'ould e *easured( #ter the :2+ *easure*ent! either 0(8*+ 809 glucose solution y gavage or 0(1 *+ e.ine.hrine intravenous IV should e ad*inistered( 5urther oservations on the ti*e 'hen tre*ors and convulsions ceased ater the ad*inistration o glucose or e.ine.hrine(
# B : %on-asted ani*alsD C B & 5asted ani*als %ote /he nor*al res.iratory rate o *ice is ?4-1>3 reaths .er *inute(
#ll asted and non-asted ani*als have u..er range and high res.iratory rate eore insulin in;ection( /hen ater insulin 'as in;ected! all ani*al su;ects have lo'er than the or*er recorded res.iratory rate exce.t or non-asted ani*al : 'hich has a higher ut 'ithin the nor*al range res.iratory rate(
G death ;ust eore lood glucose level 'as aout to e tested and ad*in o 2lu or E %7<$#+ :2+ 75 $ICE >0-130 *gFdl 3(33 A(66 **olF+ # B : %on-asted ani*als # 0(1 *l E.ine.hrine : 0(8 *l glucose C B & 5asted ani*als C 0(1 *l E.ine.hrine & 0(8 *l glucose %on asted ani*als have u..er range lood glucose level 'hile asted ani*als have *iddle range lood glucose level( #ter tre*ors and convulsions 'ere oserved! the lood glucose levels dro..ed less than the nor*al range( Ho'ever! lood glucose level asted ani*al & 'as not recorded ecause o i**ediate death( #ter the tre*ors and convulsions ceased in non-asted ani*al # e.ine.hrine induced! lood glucose elevated ut still lo'er than the nor*al range 'hile non-asted ani*al : glucose induced! and the lood glucose level slightly all y 0(1 **olF+( lood glucose levels o asted ani*als C and & 'ere not recorded ecause o sudden death(
/ale 3( /i*e 'hen tre*ors and convulsions oserved and ti*e 'hen tre*ors and convulsions ceased ater ad*inistration o glucose or e.ine.hrine #ni*al
/i*e 'hen tre*ors B /i*e 'hen tre*ors B convulsions oserved
convulsions ceased ater ad*in
o
glucose
or
e.ine.hrine #
#ter 3> *in
#ter 18 *in
:
#ter 38 *in
#ter 10 *in
C
#ter 8? *in
#ter 60 *in
&
#ter 88 *in
G
G death ;ust eore lood glucose level 'as aout to e tested and ad*in o 2lu or E # B : %on-asted ani*als # 0(1 *l E.ine.hrine : 0(8 *l glucose C B & 5asted ani*als C 0(1 *l E.ine.hrine & 0(8 *l glucose %on-asted ani*als # and : convulsed a..roxi*ately hal an hour ater insulin 'as induced 'hile non-asted ani*als C and & too) al*ost an hour eore tre*ors and convulsions 'ere oserved( /he earliest ti*e or cessation o convulsions 'as 10 *inutes and 'as oserved in non-asted ani*al : treated 'ith glucose then next 'as non-asted ani*al # treated 'ith e.ine.hrine and last 'as asted ani*al C treated 'ith e.ine.hrine( Ho'ever! duration eore cessation o convulsions 'as not oserved in asted ani*al & treated 'ith glucose due to sudden death(
Discussion Insulin .roduced y the eta cells o the .ancreas unctions *ainly in acilitating cellular u.ta)e o a*ino acids! .otassiu*! .hos.hate and *agnesiu* and y increasing the .er*eaility o cells to glucose(
5or asted ani*als since the lood glucose level is lo'! li.olysis occur( In this case! the *uscle tissue de.ends on atty acids as source o energy( /hus! there 'ould e increased consu*.tion o oxygen since it is an i*.ortant co*.onent o oxidation or #/P .roduction during cataolis*( Ideally! asted ani*als 'ould have high res.iratory rate u..er range or higher eore insulin is induced since the ody is trying to co*.ensate or the oxygen needed( /he nor*al res.iratory rate o *ice is ?4-1>3 reaths .er *inute( 5or non-asted ani*als! the .ancreas is secreting large a*ount o insulin since the lood glucose level is high( =uicient a*ount o insulin is needed to .rovide the ody 'ith its energy reuire*ent 'hile the extra insulin causes ra.id trans.ort o glucose to *uscle cells or glycogenesis( In this case! glucose is .reerred over atty acids
as source o energy( Ideally! non-asted ani*als 'ould have high res.iratory rate u..er range eore insulin is induced( #ter insulin is ad*inistered! there 'ould e interru.tion in the li.olysis through the inhiition o hor*one-sensitive li.ase 'hich is the en,y*e that causes hydrolysis o the triglycerides already stored in the at cells( #lso! there 'ould e an increased cellular u.ta)e and utili,ation o glucose( In return! these anaolic .rocesses 'ould nor*ali,e the oxygen reuire*ent o the cells( /hus! there 'ould e lo'er res.iratory rate co*.ared to the .revious res.iratory rate eore induce*ent o insulin(
5igure 4( /he role o insulin on insulin-de.endent and insulin-inde.endent cells source Pineda! $(H( 6003( $cdonalds Veterinary Endocrinology B
/he nervous syste* controls the ody organ syste*s coordination 'ith close coo.eration 'ith the endocrine syste*( 2lucose is the only energy sustrate o the rain s.eciically synthesi,ed y the *itochondria o the neuronal cell odies( :rain cells are .er*eale to glucose and do not reuire insulin as inter*ediate( /hereore! it is i*.ortant to *aintain the lood glucose level aove the critical level ecause 'hen it
alls do'n in cases o hy.oglyce*ia! central nervous syste* disorders such as sei,ures! 'ea)ness! lethargy! ataxia and strange ehaviours can occur(
In cases o *ild
hy.oglyce*ia! tre*ors and 'ea)ness are oserved 'hen the lood glucose level alls do'n to 3(3 3(@ **olF+( 7n the other hand! convulsions and shoc) can e oserved in cases o severe hy.oglyce*ia 'hen the lood glucose level dro.s to 0(@3 6(A0 **olF+( Cunningha* and JleinD 600A this is true or the otained lood glucose levels o ani*als : and C ater convulsions 'ere de*onstrated 'here in the levels are 'ithin the 0(@3 6(A0 **olF+(
5igure 8( =odiu*-.otassiu* .u*. source online(science(.su(edu 2enerally 'hen there is suicient a*ount o glucose in the rain! there 'ould e nor*al ion inlux %aKFJ K .u*.! os*olarity and *aintained hy.er.olari,ation o neurons( /he #/P driven sodiu*-.otassiu* .u*. *aintains an artiicially lo' concentration o sodiu* and high concentration o .otassiu* in the intracellular s.ace!
'hich generates a resting .otential dierence on the order o -A8 *V(
Ho'ever! 'hen there is hy.oglyce*ia or de.letion in glucose levels! the ioninlux is i*.aired resulting to sodiu* lea)age that in return 'ould cause incontrollale de.olari,ation in the neurons( /his leads to alteration in the *otor control! sensory .erce.tion! ehavior! and autono*ic unction and even da*age in the neurons( It is 'hen tre*ors! convulsions and shoc) occur( 2uyton and Hall! 600>
5igure 8( Insulin released ater induction o glucose
5igure >( 5actors aecting insulin secretion
source Pineda! $(H( 6003( $cdonalds Veterinary Endocrinology B #d*inistration o 0(8 *l 809 glucose solution triggered the eedac) *echanis* o insulin to nor*ali,e the lood glucose level and .roceed 'ith glycogenesis and li.ogenesis( /here 'ould e a direct res.onse due to the .resence o incretin in the gastrointestinal tract( 7n the other hand! ad*inistration o 0(1 *l e.ine.hrine has an antagoni,ing eect on insulin( It is a .otent inducer o glycogenolysis in the liver thus increasing the glucose levels in the lood( #s a result! there 'ould e staili,ation o the lood glucose level( /he net result o these events 'ould e staili,ation o the os*olarity and ion-inlux in the rain and thereore lead to cessation o convulsions( Ho'ever! cases o death occurred due to severe hy.oglyce*ia that led to shoc)(
References L Cunningha*! =" B :(2( Jlein( 600A( /extoo) o Veterinary Physiology( 4th ed( = Elsevier =aunders( P.( >>! >@! A6-A3 L 2uyton #C B Hall E( 600>( /extoo) o $edical Physiology(11th ed( = Elsevier =aunders Inc( .. 816! ?>6-?A3( L Pineda! $(H( 6003( $cdonalds Veterinary Endocrinology B L 8A->8?( L /he Endocrine Pancreas! &aniel E( Peavy Ph(& $edical Physiology 6nd ed( .( 8?8-8?>( L $auricio Pineda and $ichael &ooley( 6003 $c&onalds Veterinary Endocrinology and
