Literature summary for 3.4.24.56 extracted from

Maianti, J.P.; Tan, G.A.; Vetere, A.; Welsh, A.J.; Wagner, B.K.; Seeliger, M.A.; Liu, D.R.
Substrate-selective inhibitors that reprogram the activity of insulin-degrading enzyme (2019), Nat. Chem. Biol., 15, 565-574 .

Search for more literature for 3.4.24.56

Application

Application	Comment	Organism
medicine	the enzyme modulates blood glucose levels by cleaving insulin, a hormone that promotes glucose clearance. It also degrades glucagon, a hormone that elevates glucose levels and opposes the effect of insulin. Insulin-degrading enzyme inhibitors to treat diabetes, therefore, should prevent insulin-degrading enzyme-mediated insulin degradation, but not glucagon degradation. Using a high-throughput screen for non-active-site ligands, potent and highly specific small-molecule inhibitors are discovered that alter substrate selectivity of insulin-degrading enzyme. X-ray co-crystal structures, including an insulin-degrading enzyme-ligand-glucagon ternary complex, reveal substrate-dependent interactions that enable these inhibitors to potently block insulin binding while allowing glucagon cleavage, even at saturating inhibitor concentrations	Homo sapiens

Crystallization (Commentary)

Crystallization (Comment)	Organism
hanging drop vapor diffusion method, X-ray co-crystal structures, including an insulin-degrading enzyme-ligand-glucagon ternary complex, reveal substrate-dependent interactions that enable these inhibitors to potently block insulin binding while allowing glucagon cleavage, even at saturating inhibitor concentrations	Homo sapiens

Inhibitors

Inhibitors	Comment	Organism
(11R,12S,13S)-13-(hydroxymethyl)-12-(2'-methylbiphenyl-4-yl)-9-[[2-(trifluoromethyl)phenyl]sulfonyl]-1,9-diazabicyclo[9.2.0]tridecan-2-one	half-maximum effective concentration in fluorogenic decapeptide ([(7-methoxycoumarin-4-yl)acetyl]-RPPGFSAFK(Dnp)-OH) cleavage assay: 0.00006 mM	Homo sapiens
(3R,6S,9S,12E,16S)-9-(4-aminobutyl)-3-(4-benzoylbenzyl)-6-(cyclohexylmethyl)-2,5,8,11,14-pentaoxo-1,4,7,10,15-pentaazacycloicos-12-ene-16-carboxamide	half-maximum effective concentration in fluorogenic decapeptide ([(7-methoxycoumarin-4-yl)acetyl]-RPPGFSAFK(Dnp)-OH) cleavage assay: 0.00005 mM	Homo sapiens
(7R,8S,9S)-8-(2',3'-dimethylbiphenyl-4-yl)-9-(hydroxymethyl)-5-[[2-(trifluoromethyl)phenyl]sulfonyl]-1,5-diazabicyclo[5.2.0]nonan-2-one	half-maximum effective concentration in fluorogenic decapeptide ([(7-methoxycoumarin-4-yl)acetyl]-RPPGFSAFK(Dnp)-OH) cleavage assay: 0.00012 mM	Homo sapiens
(8R,9R,10S)-N-cyclopentyl-10-(hydroxymethyl)-9-(2'-methylbiphenyl-4-yl)-1,6-diazabicyclo[6.2.0]decane-6-carboxamide	the inhibitor fully blocks insulin degradation in a concentration-dependent manner, while only weakly and partially inhibiting glucagon degradation. It inhibits wild-type enzyme, but does not inhibit A479L exo-site variant. It displays decreased affinity	Homo sapiens
(8R,9S,10S)-9-(2',3'-dimethylbiphenyl-4-yl)-10-(fluoromethyl)-6-[[2-(trifluoromethyl)phenyl]sulfonyl]-1,6-diazabicyclo[6.2.0]decane	half-maximum effective concentration in fluorogenic decapeptide ([(7-methoxycoumarin-4-yl)acetyl]-RPPGFSAFK(Dnp)-OH) cleavage assay: 0.000024 mM	Homo sapiens
(8R,9S,10S)-9-(2',3'-dimethylbiphenyl-4-yl)-10-(hydroxymethyl)-6-[[2-(trifluoromethyl)phenyl]sulfonyl]-1,6-diazabicyclo[6.2.0]decan-2-one	half-maximum effective concentration in fluorogenic decapeptide ([(7-methoxycoumarin-4-yl)acetyl]-RPPGFSAFK(Dnp)-OH) cleavage assay: 0.00008 mM	Homo sapiens
(8R,9S,10S)-9-(2',3'-dimethylbiphenyl-4-yl)-10-(methoxymethyl)-6-[[2-(trifluoromethyl)phenyl]sulfonyl]-1,6-diazabicyclo[6.2.0]decane	half-maximum effective concentration in fluorogenic decapeptide ([(7-methoxycoumarin-4-yl)acetyl]-RPPGFSAFK(Dnp)-OH) cleavage assay: 0.000075 mM	Homo sapiens
(8R,9S,10S)-9-(2',3'-dimethylbiphenyl-4-yl)-6-[[2-(trifluoromethyl)phenyl]sulfonyl]-1,6-diazabicyclo[6.2.0]decane-10-carboxylic acid	half-maximum effective concentration in fluorogenic decapeptide ([(7-methoxycoumarin-4-yl)acetyl]-RPPGFSAFK(Dnp)-OH) cleavage assay: 0.0005 mM	Homo sapiens
(9R,10S,11S)-10-(2',3'-dimethylbiphenyl-4-yl)-11-(hydroxymethyl)-7-[[2-(trifluoromethyl)phenyl]sulfonyl]-1,7-diazabicyclo[7.2.0]undecan-2-one	half-maximum effective concentration in fluorogenic decapeptide ([(7-methoxycoumarin-4-yl)acetyl]-RPPGFSAFK(Dnp)-OH) cleavage assay: 0.0001 mM	Homo sapiens
1-[(8R,9R,10S)-9-(2',3'-dimethylbiphenyl-4-yl)-6-[[2-(trifluoromethyl)phenyl]sulfonyl]-1,6-diazabicyclo[6.2.0]dec-10-yl]-N,N-dimethylmethanamine	half-maximum effective concentration in fluorogenic decapeptide ([(7-methoxycoumarin-4-yl)acetyl]-RPPGFSAFK(Dnp)-OH) cleavage assay: 0.0001 mM	Homo sapiens
1-[(8R,9R,10S)-9-(2',3'-dimethylbiphenyl-4-yl)-6-[[2-(trifluoromethyl)phenyl]sulfonyl]-1,6-diazabicyclo[6.2.0]dec-10-yl]-N-methylmethanamine	half-maximum effective concentration in fluorogenic decapeptide ([(7-methoxycoumarin-4-yl)acetyl]-RPPGFSAFK(Dnp)-OH) cleavage assay: 0.000007 mM	Homo sapiens
4'-[(8R,9S,10S)-10-(hydroxymethyl)-6-[(2-methylphenyl)sulfonyl]-1,6-diazabicyclo[6.2.0]dec-9-yl]biphenyl-3-ol	half-maximum effective concentration in fluorogenic decapeptide ([(7-methoxycoumarin-4-yl)acetyl]-RPPGFSAFK(Dnp)-OH) cleavage assay: 0.0073 mM	Homo sapiens
methyl 5-[[(8R,9S,10S)-9-(2',3'-dimethylbiphenyl-4-yl)-10-(hydroxymethyl)-1,6-diazabicyclo[6.2.0]dec-6-yl]sulfonyl]-1-methyl-1H-pyrrole-2-carboxylate	half-maximum effective concentration in fluorogenic decapeptide ([(7-methoxycoumarin-4-yl)acetyl]-RPPGFSAFK(Dnp)-OH) cleavage assay: above 0.005 mM	Homo sapiens
N-(4-[[(8R,9S,10S)-9-(2',3'-dimethylbiphenyl-4-yl)-10-(hydroxymethyl)-1,6-diazabicyclo[6.2.0]dec-6-yl]sulfonyl]-3-methylphenyl)acetamide	half-maximum effective concentration in fluorogenic decapeptide ([(7-methoxycoumarin-4-yl)acetyl]-RPPGFSAFK(Dnp)-OH) cleavage assay: 0.0016 mM	Homo sapiens
N-[[(2R,3S,4S)-1-acetyl-3-(2',3'-dimethylbiphenyl-4-yl)-4-(hydroxymethyl)azetidin-2-yl]methyl]-2-(trifluoromethyl)benzenesulfonamide	half-maximum effective concentration in fluorogenic decapeptide ([(7-methoxycoumarin-4-yl)acetyl]-RPPGFSAFK(Dnp)-OH) cleavage assay: 0.000115 mM	Homo sapiens
N-[[(2R,3S,4S)-3-(2',3'-dimethylbiphenyl-4-yl)-4-(hydroxymethyl)-1-(prop-2-en-1-yl)azetidin-2-yl]methyl]-2-(trifluoromethyl)benzenesulfonamide	half-maximum effective concentration in fluorogenic decapeptide ([(7-methoxycoumarin-4-yl)acetyl]-RPPGFSAFK(Dnp)-OH) cleavage assay: 0.0001 mM	Homo sapiens
N-[[(2R,3S,4S)-3-(2',3'-dimethylbiphenyl-4-yl)-4-(hydroxymethyl)azetidin-2-yl]methyl]-2-(trifluoromethyl)benzenesulfonamide	half-maximum effective concentration in fluorogenic decapeptide ([(7-methoxycoumarin-4-yl)acetyl]-RPPGFSAFK(Dnp)-OH) cleavage assay: 0.0006 mM	Homo sapiens
N2-[(2S)-4-(hydroxyamino)-2-(naphthalen-2-ylmethyl)-4-oxobutanoyl]-L-arginyl-L-tryptophyl-L-glutamine	half-maximum effective concentration in fluorogenic decapeptide ([(7-methoxycoumarin-4-yl)acetyl]-RPPGFSAFK(Dnp)-OH) cleavage assay: 0.0000006 mM	Homo sapiens
[(3Z,8R,9S,10S)-9-(2',3'-dimethylbiphenyl-4-yl)-6-(6,7,8,9-tetrahydro-5H-imidazo[1,2-a]azepin-3-ylsulfonyl)-1,6-diazabicyclo[6.2.0]dec-3-en-10-yl]methanol	half-maximum effective concentration in fluorogenic decapeptide ([(7-methoxycoumarin-4-yl)acetyl]-RPPGFSAFK(Dnp)-OH) cleavage assay: 0.000042 mM	Homo sapiens
[(3Z,8R,9S,10S)-9-(2',3'-dimethylbiphenyl-4-yl)-6-[(1,2-dimethyl-1H-imidazol-5-yl)sulfonyl]-1,6-diazabicyclo[6.2.0]dec-3-en-10-yl]methanol	half-maximum effective concentration in fluorogenic decapeptide ([(7-methoxycoumarin-4-yl)acetyl]-RPPGFSAFK(Dnp)-OH) cleavage assay: 0.000001 mM	Homo sapiens
[(3Z,8R,9S,10S)-9-(2',3'-dimethylbiphenyl-4-yl)-6-[(1-ethyl-5-methyl-1H-pyrazol-4-yl)sulfonyl]-1,6-diazabicyclo[6.2.0]dec-3-en-10-yl]methanol	half-maximum effective concentration in fluorogenic decapeptide ([(7-methoxycoumarin-4-yl)acetyl]-RPPGFSAFK(Dnp)-OH) cleavage assay: 0.000016 mM	Homo sapiens
[(3Z,8R,9S,10S)-9-(2',3'-dimethylbiphenyl-4-yl)-6-[(1-propyl-1H-pyrazol-5-yl)sulfonyl]-1,6-diazabicyclo[6.2.0]dec-3-en-10-yl]methanol	half-maximum effective concentration in fluorogenic decapeptide ([(7-methoxycoumarin-4-yl)acetyl]-RPPGFSAFK(Dnp)-OH) cleavage assay: 0.000018 mM	Homo sapiens
[(3Z,8R,9S,10S)-9-(2',3'-dimethylbiphenyl-4-yl)-6-[(2-methylpyridin-3-yl)sulfonyl]-1,6-diazabicyclo[6.2.0]dec-3-en-10-yl]methanol	half-maximum effective concentration in fluorogenic decapeptide ([(7-methoxycoumarin-4-yl)acetyl]-RPPGFSAFK(Dnp)-OH) cleavage assay: 0.000022 mM	Homo sapiens
[(3Z,8R,9S,10S)-9-(2',3'-dimethylbiphenyl-4-yl)-6-[[1-methyl-3-(trifluoromethyl)-1H-pyrazol-4-yl]sulfonyl]-1,6-diazabicyclo[6.2.0]dec-3-en-10-yl]methanol	half-maximum effective concentration in fluorogenic decapeptide ([(7-methoxycoumarin-4-yl)acetyl]-RPPGFSAFK(Dnp)-OH) cleavage assay: 0.000065 mM	Homo sapiens
[(8R,9S,10S)-6-(cyclohexylsulfonyl)-9-(2',3'-dimethylbiphenyl-4-yl)-1,6-diazabicyclo[6.2.0]dec-10-yl]methanol	half-maximum effective concentration in fluorogenic decapeptide ([(7-methoxycoumarin-4-yl)acetyl]-RPPGFSAFK(Dnp)-OH) cleavage assay: 0.00046 mM	Homo sapiens
[(8R,9S,10S)-6-[(2-methylphenyl)sulfonyl]-9-[2'-methyl-3'-(trifluoromethyl)biphenyl-4-yl]-1,6-diazabicyclo[6.2.0]dec-10-yl]methanol	half-maximum effective concentration in fluorogenic decapeptide ([(7-methoxycoumarin-4-yl)acetyl]-RPPGFSAFK(Dnp)-OH) cleavage assay: 0.000095 mM	Homo sapiens
[(8R,9S,10S)-9-(2',3'-dichlorobiphenyl-4-yl)-6-[(2-methylphenyl)sulfonyl]-1,6-diazabicyclo[6.2.0]dec-10-yl]methanol	half-maximum effective concentration in fluorogenic decapeptide ([(7-methoxycoumarin-4-yl)acetyl]-RPPGFSAFK(Dnp)-OH) cleavage assay: 0.000009 mM	Homo sapiens
[(8R,9S,10S)-9-(2',3'-dimethylbiphenyl-4-yl)-6-[(1,3-dimethyl-1H-pyrazol-5-yl)sulfonyl]-1,6-diazabicyclo[6.2.0]dec-10-yl]methanol	half-maximum effective concentration in fluorogenic decapeptide ([(7-methoxycoumarin-4-yl)acetyl]-RPPGFSAFK(Dnp)-OH) cleavage assay: 0.000024 mM	Homo sapiens
[(8R,9S,10S)-9-(2',3'-dimethylbiphenyl-4-yl)-6-[(1-methyl-1H-imidazol-2-yl)sulfonyl]-1,6-diazabicyclo[6.2.0]dec-10-yl]methanol	half-maximum effective concentration in fluorogenic decapeptide ([(7-methoxycoumarin-4-yl)acetyl]-RPPGFSAFK(Dnp)-OH) cleavage assay: 0.0000005 mM	Homo sapiens
[(8R,9S,10S)-9-(2',3'-dimethylbiphenyl-4-yl)-6-[(1-methyl-1H-pyrazol-5-yl)sulfonyl]-1,6-diazabicyclo[6.2.0]dec-10-yl]methanol	half-maximum effective concentration in fluorogenic decapeptide ([(7-methoxycoumarin-4-yl)acetyl]-RPPGFSAFK(Dnp)-OH) cleavage assay: 0.00006 mM	Homo sapiens
[(8R,9S,10S)-9-(2',3'-dimethylbiphenyl-4-yl)-6-[(2-methylphenyl)sulfonyl]-1,6-diazabicyclo[6.2.0]dec-10-yl]methanol	half-maximum effective concentration in fluorogenic decapeptide ([(7-methoxycoumarin-4-yl)acetyl]-RPPGFSAFK(Dnp)-OH) cleavage assay: 0.0000015 mM	Homo sapiens
[(8R,9S,10S)-9-(2',3'-dimethylbiphenyl-4-yl)-6-[(4-methylpiperazin-1-yl)sulfonyl]-1,6-diazabicyclo[6.2.0]dec-10-yl]methanol	half-maximum effective concentration in fluorogenic decapeptide ([(7-methoxycoumarin-4-yl)acetyl]-RPPGFSAFK(Dnp)-OH) cleavage assay: 0.000032 mM	Homo sapiens
[(8R,9S,10S)-9-(2',3'-dimethylbiphenyl-4-yl)-6-[[1-(propan-2-yl)-1H-pyrazol-5-yl]sulfonyl]-1,6-diazabicyclo[6.2.0]dec-10-yl]methanol	half-maximum effective concentration in fluorogenic decapeptide ([(7-methoxycoumarin-4-yl)acetyl]-RPPGFSAFK(Dnp)-OH) cleavage assay: 0.000015 mM	Homo sapiens
[(8R,9S,10S)-9-(2',3'-dimethylbiphenyl-4-yl)-6-[[2-(trifluoromethyl)phenyl]sulfonyl]-1,6-diazabicyclo[6.2.0]dec-10-yl]methanol	half-maximum effective concentration in fluorogenic decapeptide ([(7-methoxycoumarin-4-yl)acetyl]-RPPGFSAFK(Dnp)-OH) cleavage assay: 0.000001 mM	Homo sapiens
[(8R,9S,10S)-9-(2',5'-dimethylbiphenyl-4-yl)-6-[(2-methylphenyl)sulfonyl]-1,6-diazabicyclo[6.2.0]dec-10-yl]methanol	half-maximum effective concentration in fluorogenic decapeptide ([(7-methoxycoumarin-4-yl)acetyl]-RPPGFSAFK(Dnp)-OH) cleavage assay: 0.000054 mM	Homo sapiens
[(8R,9S,10S)-9-(2'-methoxybiphenyl-4-yl)-6-[(2-methylphenyl)sulfonyl]-1,6-diazabicyclo[6.2.0]dec-10-yl]methanol	half-maximum effective concentration in fluorogenic decapeptide ([(7-methoxycoumarin-4-yl)acetyl]-RPPGFSAFK(Dnp)-OH) cleavage assay: 0.00025 mM	Homo sapiens
[(8R,9S,10S)-9-(2'-methylbiphenyl-4-yl)-6-[(2-methylphenyl)sulfonyl]-1,6-diazabicyclo[6.2.0]dec-10-yl]methanol	half-maximum effective concentration in fluorogenic decapeptide ([(7-methoxycoumarin-4-yl)acetyl]-RPPGFSAFK(Dnp)-OH) cleavage assay: 0.000032 mM	Homo sapiens
[(8R,9S,10S)-9-(3',4'-dimethylbiphenyl-4-yl)-6-[(2-methylphenyl)sulfonyl]-1,6-diazabicyclo[6.2.0]dec-10-yl]methanol	half-maximum effective concentration in fluorogenic decapeptide ([(7-methoxycoumarin-4-yl)acetyl]-RPPGFSAFK(Dnp)-OH) cleavage assay: 0.00014 mM	Homo sapiens
[(8R,9S,10S)-9-(3',5'-dimethylbiphenyl-4-yl)-6-[(2-methylphenyl)sulfonyl]-1,6-diazabicyclo[6.2.0]dec-10-yl]methanol	half-maximum effective concentration in fluorogenic decapeptide ([(7-methoxycoumarin-4-yl)acetyl]-RPPGFSAFK(Dnp)-OH) cleavage assay: 0.000061 mM	Homo sapiens
[(8R,9S,10S)-9-(3'-chloro-2'-methylbiphenyl-4-yl)-6-[(2-methylphenyl)sulfonyl]-1,6-diazabicyclo[6.2.0]dec-10-yl]methanol	half-maximum effective concentration in fluorogenic decapeptide ([(7-methoxycoumarin-4-yl)acetyl]-RPPGFSAFK(Dnp)-OH) cleavage assay: 0.000035 mM	Homo sapiens
[(8R,9S,10S)-9-(3'-fluoro-2'-methylbiphenyl-4-yl)-6-[(2-methylphenyl)sulfonyl]-1,6-diazabicyclo[6.2.0]dec-10-yl]methanol	half-maximum effective concentration in fluorogenic decapeptide ([(7-methoxycoumarin-4-yl)acetyl]-RPPGFSAFK(Dnp)-OH) cleavage assay: 0.00007 mM	Homo sapiens
[(8R,9S,10S)-9-(3'-fluorobiphenyl-4-yl)-6-[(2-methylphenyl)sulfonyl]-1,6-diazabicyclo[6.2.0]dec-10-yl]methanol	half-maximum effective concentration in fluorogenic decapeptide ([(7-methoxycoumarin-4-yl)acetyl]-RPPGFSAFK(Dnp)-OH) cleavage assay: 0.00007 mM	Homo sapiens
[(8R,9S,10S)-9-(3'-methoxybiphenyl-4-yl)-6-[(2-methylphenyl)sulfonyl]-1,6-diazabicyclo[6.2.0]dec-10-yl]methanol	half-maximum effective concentration in fluorogenic decapeptide ([(7-methoxycoumarin-4-yl)acetyl]-RPPGFSAFK(Dnp)-OH) cleavage assay: 0.0005 mM	Homo sapiens
[(8R,9S,10S)-9-(3'-methylbiphenyl-4-yl)-6-[(2-methylphenyl)sulfonyl]-1,6-diazabicyclo[6.2.0]dec-10-yl]methanol	the inhibitor fully blocks insulin degradation in a concentration-dependent manner, while only weakly and partially inhibiting glucagon degradation. It inhibits wild-type enzyme, but does not inhibit A479L exo-site variant. It displays decreased affinity	Homo sapiens
[(8R,9S,10S)-9-(biphenyl-4-yl)-6-[(2-methylphenyl)sulfonyl]-1,6-diazabicyclo[6.2.0]dec-10-yl]methanol	half-maximum effective concentration in fluorogenic decapeptide ([(7-methoxycoumarin-4-yl)acetyl]-RPPGFSAFK(Dnp)-OH) cleavage assay: 0.0004 mM	Homo sapiens
[(8R,9S,10S)-9-[3'-fluoro-2'-(trifluoromethyl)biphenyl-4-yl]-6-[(2-methylphenyl)sulfonyl]-1,6-diazabicyclo[6.2.0]dec-10-yl]methanol	half-maximum effective concentration in fluorogenic decapeptide ([(7-methoxycoumarin-4-yl)acetyl]-RPPGFSAFK(Dnp)-OH) cleavage assay: 0.00017 mM	Homo sapiens
[(8R,9S,10S)-9-[4-(1,3-benzodioxol-5-yl)phenyl]-6-[(2-methylphenyl)sulfonyl]-1,6-diazabicyclo[6.2.0]dec-10-yl]methanol	half-maximum effective concentration in fluorogenic decapeptide ([(7-methoxycoumarin-4-yl)acetyl]-RPPGFSAFK(Dnp)-OH) cleavage assay: 0.0029 mM	Homo sapiens

Natural Substrates/ Products (Substrates)

Natural Substrates	Organism	Comment (Nat. Sub.)	Natural Products	Comment (Nat. Pro.)	Rev.	Reac.
Glucagon + H2O	Homo sapiens	the enzyme modulates blood glucose levels by cleaving insulin, a hormone that promotes glucose clearance. It also degrades glucagon, a hormone that elevates glucose levels and opposes the effect of insulin	?	-	?
insulin + H2O	Homo sapiens	the enzyme modulates blood glucose levels by cleaving insulin, a hormone that promotes glucose clearance. It also degrades glucagon, a hormone that elevates glucose levels and opposes the effect of insulin	?	-	?

Organism

Organism	UniProt	Comment	Textmining
Homo sapiens	P14735	-	-

Substrates and Products (Substrate)

Substrates	Comment Substrates	Organism	Products	Comment (Products)	Rev.
Glucagon + H2O	-	Homo sapiens	?	-	?
Glucagon + H2O	the enzyme modulates blood glucose levels by cleaving insulin, a hormone that promotes glucose clearance. It also degrades glucagon, a hormone that elevates glucose levels and opposes the effect of insulin	Homo sapiens	?	-	?
insulin + H2O	-	Homo sapiens	?	-	?
insulin + H2O	the enzyme modulates blood glucose levels by cleaving insulin, a hormone that promotes glucose clearance. It also degrades glucagon, a hormone that elevates glucose levels and opposes the effect of insulin	Homo sapiens	?	-	?
[(7-methoxycoumarin-4-yl)acetyl]-RPPGFSAFK(Dnp)-OH + H2O	-	Homo sapiens	[(7-methoxycoumarin-4-yl)acetyl]-RPPGF + SAFK(Dnp)-OH	-	ir

Synonyms

Synonyms	Comment	Organism
IDE	-	Homo sapiens
Insulin-degrading enzyme	-	Homo sapiens

General Information

General Information	Comment	Organism
metabolism	the enzyme modulates blood glucose levels by cleaving insulin, a hormone that promotes glucose clearance. It also degrades glucagon, a hormone that elevates glucose levels and opposes the effect of insulin	Homo sapiens