NEUROENDOCRINOLOGY
LETTERS
including
Psychoneuroimmunology, Neuropsychopharmacology,
Reproductive Medicine, Chronobiology
and Human Ethology, ISSN 0172–780X
OBJECTIVE:
Diabetes Mellitus is associated with decreased insulin-like
growth factor-I (IGF-I) levels and also, poor growth in diabetes
is related with low circulating levels of IGF-I. Insulin acts
via an increase of IGF-I synthesis on growth. We studied the
effects of insulin and sulphonylureas on serum IGF-I levels
and aimed to evaluate the restoration of IGF-I in different
therapeutic strategies.
DESIGN
AND SETTING: Thirty male rats were used in the study and diabetes
was induced by a single intraperitoneal injection of streptozotocin
(35 mg/kg body weight). After confirmation of hyperglycemia,
rats were divided into three groups. The first group was treated
with insulin, and second group with glimepiride, third group
was not treated (control group). IGF-I levels were measured
at basal, after streptozotocin and at the end of the treatment
period.
RESULTS:
Serum IGF-I levels were found to decrease from 577.2 ng/ml
to 253.0 ng/ml after streptozotocin (p<0.005). After 1
month, IGF-1 levels were found 524.0 ng/ml in insulin group,
449.3 ng/ml in sulphonylurea group, and 313.1 ng/ml in control
group. The increase in IGF-I was statistically significant
in insulin group (p<0.005), and in sulphonylurea group
(p<0.05), but it was not significant in control group (p>0.05).
CONCLUSIONS:
Serum IGF-I levels decrease in diabetes and insulin treatment
restores IGF-I depletion significantly. And although less
effective, treatment with glimepiride restores IGF-I levels
significantly.
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Introduction
Diabetes
Mellitus is associated with decreased insulin-like growth factor-I
(IGF-I) levels [1,2] and poor growth in diabetes is related
with low circulating levels of IGF-I [3]. Also multiple factors
contribute to the growth retardation which is a characteristic
feature of uncontrolled diabetes, diminished IGF-I expression
and inhibition of available IGF-I may explain the impaired growth
in diabetics [4].
Studies in diabetic rodents and humans provide evidence that
IGF-I may alleviate the diabetic state and insulin resistance
to some degree [5]. More recent studies focused on the role
of IGF-I deficiency as a contributing factor to the metabolic
dysfunction in patients with diabetes [6]. Recombinant human
insulin-like growth factor-I (rhIGF-I) was found to improve
glycemic control and enhance insulin sensitivity in patients
with severe insulin resistance [7–9]. IGF-I has good metabolic
effects on glucose uptake and production in diabetic rats in
which insulin-stimulated glucose uptake was impaired [10]. Further,
IGF-I potently inhibits the secretion of insulin from pancreatic
beta-cells, which appear to possess IGF-I but not insulin receptors
[11–13].
It
was shown that growth arrest in the diabetic rats was corrected
by insulin infusion which also restored growth hormone secretion
[14–16]. Insulin-deficient growth-arrested diabetic animals
have reduced serum IGF-I levels which are restored towards normal
by insulin but not by growth-hormone treatment. Normal growth
of diabetic rat is restored by infusion of recombinant human
IGF-I without normalization of the blood sugar level and that
insulin acts via an increase of IGF-I synthesis on growth of
diabetic rats [17]. But, there is no sufficient data about the
effects of sulphonylureas on IGF-I levels in diabetics. In a
study, Heinze et al found that glibenclamide promotes the growth
of human chondrocytes in culture and concluded that this effect
is mediated by IGF-I dependent mechanisms [18]. We studied the
effects of insulin and sulphonylureas on serum IGF-I levels
and aimed to evaluate the restoration of IGF-I in different
therapeutic strategies.
