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To model the type 1 DM that is characterized by absolute insulin deficit and strongly expressed

hyperglycemia, we have used the widely spread streptozotocin model that was induced by the single
injection to rats of a high dose of streptozotocin (60–75 mg/kg weight) [16, 17]. Duration of this
acute type 1 DM model amounted to from 7 to 30 days, as one month after its induction the death
of the significant part of diabetic animals is usually observed. Alongside with this, we have
developed and used successfully the milder, prolonged model of the type 1 DM induced by several
consecutive injections of the moderate streptozotocin injections (30–40 mg/kg weight) [18, 19].
Since hyperglycemia in the mild model is not as pronounced as in the acute model of the type 1 DM,
which is a consequence not of absolute, but of relative insulin deficit, the lifespan of animals with
the mild model amounted to 6 months and more after the first streptozotocin injection. Such
prolonged model allowed observing development of the type 1 DM complications from the
cardiovascular, reproductive, and nervous systems, which are developing no sooner than 2–3
months after induction of the disease. To model the type 2 DM characterized by tissue resistance to
insulin and moderate hyperglycemia, we used the neonatal caused by the single injection to
newborn rat pups of streptozotocin at a dose of 85 mg/kg weight [20–22].

As the main object for molecular-endocrinological studies, we have chosen the hormonesensitive
adenylyl cyclase signaling system (ACS), through which their regulatory action on the cell is produced
by hundreds of hormones differing by chemical structure and by numerous hormonelike substances.
ACS is involved in regulation of a wide spectrum of fundamental cellular processes, such as growth,
metabolism, apoptosis, differentiation, movement, and chemotaxis. The choice of ACS was also due
to that as early as in the 1980s– 1990s we obtained numerous data about that in the type 1 DM in
tissues of the cardiovascular system, in the adipose tissue, in muscle and liver the functional activity
of this system and its regulation by hormones strongly change [2, 25]. Also important is that at our
laboratory for more than 30 years, intensive studies of the structural-functional organization and
hormonal sensitivity of ACS have been carried out in animals of different phylogenetic level and
there were discovered novel mechanisms of action of insulin and its related peptides on intracellular
cAMP-d

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