300
8 Peptide Hormones
immunologically in Neurospora and Streptococcus [50], and insulin-like peptides have been
sequenced via their cDNA in the snail Lymnaea
stagnalis and the insects Bombyx mori and
Locusta migratoria (p.307). Only in the case of
the insects have sufficient quantities of insulinlike peptides been isolated with which to study
activity. In the honey bee, reinjection of the peptide brings about a reduction in the concentrations of trehalose, glucose, diacylglycerols and
phospholipids, and an increase in free fatty acids
and triacylglycerols in the haemolymph. As in the
vertebrates, these typical insulin effects are inhibited by the simultaneous injection of vertebrate
somatostatin [22]. Drosophila melanogaster possesses not only a typical insulin receptor but also
a specific insulin protease like those known in
mammals; this suggests specific functions for
insulin in the fly [56, 63].
Insulin belongs to the same super-family as the
ovarian hormone relaxin, the insulin-like growth
factors IGF-I and IGF-II (somatome dins) , and
probably also the B chain of the nerve growth factor (NFG) and the lens growth factor lentropin
[8]. Relaxins synthesized in the ovary and also in
the uterus and placenta are made up of an
A chain of 22-24 and a B chain of 25-35 amino
acids, and are considered to be homologous to
the insulins, especially because of the positions of
the disulphide bridges. In mammals, relaxin is
responsible for adaptation of the uterus musculature to the foetus and for expansion of the pubic
bone symphysis prior to birth [197]. The two
human relaxins have only 77 % sequence agreement. Relaxins are already found in the cartilaginous fish, the relaxins of the shark species
Squalus acanthias and Odontaspis taurus being
45-46 % similar to human relaxin; the relaxins of
the pig and rat show an equivalent degree of similarity. The relaxin of the skate Raja erinacea,
which has 48 % amino acids in common with that
of Squalus and 31 % with human relaxin, has only
1 % of the activity of mammalian relaxin when
tested on mammals [28]. Relaxin-like substances
are even found in the ciliate Tetrahymena pyriformis. It also appears from this that the substance is
much older than its present function in the mammals. The observation that the insulin activity of
organ extracts is often not completely abolished
by anti-insulin antibodies led to the discovery of
the insulin-like growth factors (IGFs). There are
two IGFs (IGF-I and IGF-II) and corresponding
specific receptors. Both IGFs bind to the insulin
receptor, but insulin itself binds only to the IGF-I
receptor and not to that of IGF-II. IGF-I (with
70 amino acids) shows more than 60 % sequence
similarity with IGF-II (67 amino acids). The three
regions B, C and A are distinguishable in the IGF
precursors, as in pro-insulins, but they are
extended at the C-terminus by a short D region
and an E region, which consists of about 35
amino acids in pro-IGF-I and of 85-90 amino
acids in pro-IGF-II. Region E is removed during
IGF processing, but sections C and D remain in
the mature molecule. The IGFs are bound to specific proteins in the blood plasma, possibly in
order to prevent interaction with receptors, e.g.
the IGF concentration of 100 nmoUl in human
plasma is lOOO-fold higher than that of insulin and
would have a 50-fold higher insulin activity
[85, 119]. IGFs are known from vertebrates of all
classes down to the Atlantic hagfish Myxine glutinosa [150]. The acranian Branchiostoma californiensis has an insulin-like peptide (ILP) which
has approximately the same sequence similarity
to insulin in both IGFs, and arises from a precursor with the regions B-C-A-D-E; thus, it is
apparently very closely related to the ancestral
gene of the insulin family [32].
8.4.3 The Glucagon-Secretin Family
Glucagon, glicentin and secretin, together with
the vasoactive intestinal peptide (VIP), the
gastric inhibitory peptide (GIP) , the growthhormone releasing factor (GRF) and the helospectins in the poison of the venomous lizard
Heloderma suspectum (p. 324), make up a family
of peptides with 9-15 of their 27-43 amino acids
in common (Fig. 8.2 k) but with widely varying
activities. Glucagon and glicentin stimulate gluconeogenesis and glycogenolysis, whereas secretin, VIP and the helospectins promote secretion
from the pancreas. In addition, VIP brings about
relaxation of the vascular and other smooth
muscles; GIP inhibits acid and pepsin formation
in the stomach. The glucagon secreted by the
A cells of the islets tissue and the glicentin produced by the L cells of the gut mucosa arise from
the same precursor by differential proteolytic
cleavage. The human precursor and that of various mammals has a length of 180 amino acids and
consists of a signal sequence, glicentin with 69 amino acids, including the glucagon sequence in
positions 33-61, and two glucagon-like sequences
GLP-1 and GLP-2. The angler fish Lophius americanus possesses two glucagon genes which, however, lack the GLP-2 region [3, 161]. The teleosts
Ictalurus punctata, Oncorhynchus kisutch and
8 Peptide Hormones
immunologically in Neurospora and Streptococcus [50], and insulin-like peptides have been
sequenced via their cDNA in the snail Lymnaea
stagnalis and the insects Bombyx mori and
Locusta migratoria (p.307). Only in the case of
the insects have sufficient quantities of insulinlike peptides been isolated with which to study
activity. In the honey bee, reinjection of the peptide brings about a reduction in the concentrations of trehalose, glucose, diacylglycerols and
phospholipids, and an increase in free fatty acids
and triacylglycerols in the haemolymph. As in the
vertebrates, these typical insulin effects are inhibited by the simultaneous injection of vertebrate
somatostatin [22]. Drosophila melanogaster possesses not only a typical insulin receptor but also
a specific insulin protease like those known in
mammals; this suggests specific functions for
insulin in the fly [56, 63].
Insulin belongs to the same super-family as the
ovarian hormone relaxin, the insulin-like growth
factors IGF-I and IGF-II (somatome dins) , and
probably also the B chain of the nerve growth factor (NFG) and the lens growth factor lentropin
[8]. Relaxins synthesized in the ovary and also in
the uterus and placenta are made up of an
A chain of 22-24 and a B chain of 25-35 amino
acids, and are considered to be homologous to
the insulins, especially because of the positions of
the disulphide bridges. In mammals, relaxin is
responsible for adaptation of the uterus musculature to the foetus and for expansion of the pubic
bone symphysis prior to birth [197]. The two
human relaxins have only 77 % sequence agreement. Relaxins are already found in the cartilaginous fish, the relaxins of the shark species
Squalus acanthias and Odontaspis taurus being
45-46 % similar to human relaxin; the relaxins of
the pig and rat show an equivalent degree of similarity. The relaxin of the skate Raja erinacea,
which has 48 % amino acids in common with that
of Squalus and 31 % with human relaxin, has only
1 % of the activity of mammalian relaxin when
tested on mammals [28]. Relaxin-like substances
are even found in the ciliate Tetrahymena pyriformis. It also appears from this that the substance is
much older than its present function in the mammals. The observation that the insulin activity of
organ extracts is often not completely abolished
by anti-insulin antibodies led to the discovery of
the insulin-like growth factors (IGFs). There are
two IGFs (IGF-I and IGF-II) and corresponding
specific receptors. Both IGFs bind to the insulin
receptor, but insulin itself binds only to the IGF-I
receptor and not to that of IGF-II. IGF-I (with
70 amino acids) shows more than 60 % sequence
similarity with IGF-II (67 amino acids). The three
regions B, C and A are distinguishable in the IGF
precursors, as in pro-insulins, but they are
extended at the C-terminus by a short D region
and an E region, which consists of about 35
amino acids in pro-IGF-I and of 85-90 amino
acids in pro-IGF-II. Region E is removed during
IGF processing, but sections C and D remain in
the mature molecule. The IGFs are bound to specific proteins in the blood plasma, possibly in
order to prevent interaction with receptors, e.g.
the IGF concentration of 100 nmoUl in human
plasma is lOOO-fold higher than that of insulin and
would have a 50-fold higher insulin activity
[85, 119]. IGFs are known from vertebrates of all
classes down to the Atlantic hagfish Myxine glutinosa [150]. The acranian Branchiostoma californiensis has an insulin-like peptide (ILP) which
has approximately the same sequence similarity
to insulin in both IGFs, and arises from a precursor with the regions B-C-A-D-E; thus, it is
apparently very closely related to the ancestral
gene of the insulin family [32].
8.4.3 The Glucagon-Secretin Family
Glucagon, glicentin and secretin, together with
the vasoactive intestinal peptide (VIP), the
gastric inhibitory peptide (GIP) , the growthhormone releasing factor (GRF) and the helospectins in the poison of the venomous lizard
Heloderma suspectum (p. 324), make up a family
of peptides with 9-15 of their 27-43 amino acids
in common (Fig. 8.2 k) but with widely varying
activities. Glucagon and glicentin stimulate gluconeogenesis and glycogenolysis, whereas secretin, VIP and the helospectins promote secretion
from the pancreas. In addition, VIP brings about
relaxation of the vascular and other smooth
muscles; GIP inhibits acid and pepsin formation
in the stomach. The glucagon secreted by the
A cells of the islets tissue and the glicentin produced by the L cells of the gut mucosa arise from
the same precursor by differential proteolytic
cleavage. The human precursor and that of various mammals has a length of 180 amino acids and
consists of a signal sequence, glicentin with 69 amino acids, including the glucagon sequence in
positions 33-61, and two glucagon-like sequences
GLP-1 and GLP-2. The angler fish Lophius americanus possesses two glucagon genes which, however, lack the GLP-2 region [3, 161]. The teleosts
Ictalurus punctata, Oncorhynchus kisutch and