Whey proteins and their hydrolysates showed to affect blood glucose control and
insulinotropic response positively in humans when administrated orally, and
therefore, can be useful in type 2 diabetes control and therapy [93]. Although not
fully understood, the effects of whey proteins and their hydrolysates on glycemia
seem to be mediated, in vivo, by stimulating the secretion of intestinal hormones,
acting also as inhibitors of the enzymes, dipeptidyl peptidase IV (DPP IV) and
a-glucosidase.
Kehinde and Sharma [94] recently reviewed the antidiabetic properties of
hydrolysates and peptides from multiple food sources.
5.2.1 Inhibition of the DPP IV Enzyme
Several proteins are considered as precursors of peptide inhibitors of the enzyme
DPP IV and thus able to regulate plasma levels of hormones, the glucagon-like
peptide 1 (GLP1), and the glucose-dependent insulinotropic polypeptide (GIP),
both substrates of DPP IV enzyme [95]. In fact, in silico approaches revealed
several encrypted peptides within the amino acid sequences of dietary proteins that
could act as DPP IV inhibitors. Peptides identified as DPP IV inhibitors from those
protein hydrolysates usually have molecular weights below 2 kDa. Most of them
contain Proline amino acid residues and or hydrophobic ones within their sequence,
which play a more significant role [96, 97]. Additionally, the inhibitory abilities of
peptide seem to result from competitive, un-competitive, or non-competitive modes
of inhibition of DPP IV enzyme.
The in vitro evaluation of the synthesized peptide IPA, identified after the
digestion of b-LG protein with proteinase K, demonstrated its ability to inhibit the
DPP IV enzyme competitively [98]. Similarly, the peptide IPAVFKIDAL released
from a-LA was also reported to exhibit competitive inhibition of DPP IV enzyme,
which can result from its structural similarity to the enzyme–substrate. Peptides
LAHKALCSEKsL and ILDKVGINY released from a-LA also inhibited DPP IV
by direct interaction with the active sites of the enzyme. On the contrary, Lacroix
and Li-Chan [99] observed that the peptides LKPTPEGDL and LKPTPEGDLEIL
released from b-LG showed to be among others, the most potent DPP IV inhibitors
identified from whey protein hydrolysates. These peptides seem to act according to
the mode of un-competitive inhibition on DPP IV, that is, they probably bind to the
enzyme–substrate complex when formed, but outside the active site and thus
decreasing the catalytic activity of the DPP IV enzyme.
Additionally, the peptide WLAHKALCSEKLDQ released from a-LA exhibited
an un-competitive inhibitory behavior. Besides, peptides WLAHKAL and
LCSEKLDQWL were reported as non-competitive inhibitors, binding outside the
catalytic center of DPP IV enzyme or to the enzyme–substrate complex. The
structure–activity relationships and the exact mechanisms by which whey-derived
peptides inhibit the DPP IV enzyme are not yet fully elucidated [95].
Conventional synthetic drugs such as Diprotin A (IPI), Diprotin B (VPL), and
Sitagliptin are the most potent inhibitors of DPP IV enzyme. They are more potent
than individual peptides present in whey protein hydrolysates. Thus, the above
example of bioactive peptides from whey protein hydrolysates cannot replace the
Enzymatic Production of Bioactive Peptides from Whey Proteins …
493
insulinotropic response positively in humans when administrated orally, and
therefore, can be useful in type 2 diabetes control and therapy [93]. Although not
fully understood, the effects of whey proteins and their hydrolysates on glycemia
seem to be mediated, in vivo, by stimulating the secretion of intestinal hormones,
acting also as inhibitors of the enzymes, dipeptidyl peptidase IV (DPP IV) and
a-glucosidase.
Kehinde and Sharma [94] recently reviewed the antidiabetic properties of
hydrolysates and peptides from multiple food sources.
5.2.1 Inhibition of the DPP IV Enzyme
Several proteins are considered as precursors of peptide inhibitors of the enzyme
DPP IV and thus able to regulate plasma levels of hormones, the glucagon-like
peptide 1 (GLP1), and the glucose-dependent insulinotropic polypeptide (GIP),
both substrates of DPP IV enzyme [95]. In fact, in silico approaches revealed
several encrypted peptides within the amino acid sequences of dietary proteins that
could act as DPP IV inhibitors. Peptides identified as DPP IV inhibitors from those
protein hydrolysates usually have molecular weights below 2 kDa. Most of them
contain Proline amino acid residues and or hydrophobic ones within their sequence,
which play a more significant role [96, 97]. Additionally, the inhibitory abilities of
peptide seem to result from competitive, un-competitive, or non-competitive modes
of inhibition of DPP IV enzyme.
The in vitro evaluation of the synthesized peptide IPA, identified after the
digestion of b-LG protein with proteinase K, demonstrated its ability to inhibit the
DPP IV enzyme competitively [98]. Similarly, the peptide IPAVFKIDAL released
from a-LA was also reported to exhibit competitive inhibition of DPP IV enzyme,
which can result from its structural similarity to the enzyme–substrate. Peptides
LAHKALCSEKsL and ILDKVGINY released from a-LA also inhibited DPP IV
by direct interaction with the active sites of the enzyme. On the contrary, Lacroix
and Li-Chan [99] observed that the peptides LKPTPEGDL and LKPTPEGDLEIL
released from b-LG showed to be among others, the most potent DPP IV inhibitors
identified from whey protein hydrolysates. These peptides seem to act according to
the mode of un-competitive inhibition on DPP IV, that is, they probably bind to the
enzyme–substrate complex when formed, but outside the active site and thus
decreasing the catalytic activity of the DPP IV enzyme.
Additionally, the peptide WLAHKALCSEKLDQ released from a-LA exhibited
an un-competitive inhibitory behavior. Besides, peptides WLAHKAL and
LCSEKLDQWL were reported as non-competitive inhibitors, binding outside the
catalytic center of DPP IV enzyme or to the enzyme–substrate complex. The
structure–activity relationships and the exact mechanisms by which whey-derived
peptides inhibit the DPP IV enzyme are not yet fully elucidated [95].
Conventional synthetic drugs such as Diprotin A (IPI), Diprotin B (VPL), and
Sitagliptin are the most potent inhibitors of DPP IV enzyme. They are more potent
than individual peptides present in whey protein hydrolysates. Thus, the above
example of bioactive peptides from whey protein hydrolysates cannot replace the
Enzymatic Production of Bioactive Peptides from Whey Proteins …
493