Insulin secretion, peripheral insulin sensitivity and insulin-receptor binding in subjects with different degrees of obesity.
OBJECTIVE
The aim of the present study was to investigate insulin secretion, insulin-receptor binding and peripheral insulin sensitivity in subjects with different degrees of obesity.


METHODS
36 obese subjects with normal glucose tolerance and different degrees of obesity and 40 healthy normal-weight subjects participated in the study. Peripheral insulin sensitivity was measured by using the euglycaemic hyperinsulinaemic clamp technique, and insulin-receptor binding-on circulating mononuclear blood cells. Insulin secretion was studied during intravenous tolbutamide test.


RESULTS
The subjects with I degree of obesity demonstrated a significant decrease in the number of total (p<0.0001) and high-affinity (p<0.01) insulin receptors per cell, as well as significantly higher insulin receptor affinity (p<0.01) as compared to the normal-weight subjects. The subjects with II degree of obesity also demonstrated a significant decrease in the number of total (p<0.0001) and high-affinity receptors (p<0.001) per cell as well as an increase (p<0.001) in insulin-receptor affinity as compared to the controls. The significantly decreased receptor number in the subjects with I and II degree of obesity was accompanied by an increase in insulin receptor affinity; thus their insulin-receptor binding being maintained similar to the controls. The subjects with III degree obesity presented a significant decrease (p<0.0001) in the number of both the total and high-affinity insulin receptors as well as a reduction in insulin receptor affinity as compared to the controls. Therefore the percentage of specifically bound insulin was significantly lower (p<0.01) as compared to that of the control group. Insulin resistance in the obese subjects is associated with secondary hyperinsulinaemia, which is present in subjects with I and II degree of obesity; while in severely obese subjects exhaustion of beta-cell secretory capacity is observed.


CONCLUSIONS
We consider that III degree of obesity appears to be a risk factor for type 2 diabetes mellitus as the alterations in insulin sensitivity, insulin-receptor binding and beta-cell secretion are quite similar to the reported in diabetic patients.
Borissova
A M
AM
Clinical Centre of Endocrinology, Medical University, Sofia, Bulgaria. blpo98@internet-bg.net
Tankova
T I
TI
Koev
D J
DJ
D019540:Area Under Curve; D001786:Blood Glucose / Q000378:metabolism*; D001835:Body Weight; D005951:Glucose Tolerance Test; D006801:Humans; D006946:Hyperinsulinism / Q000097:blood; D007328:Insulin / Q000097:blood / Q000378:metabolism* / Q000494:pharmacology; D007333:Insulin Resistance; D000078790:Insulin Secretion; D009765:Obesity / Q000097:blood / Q000145:classification / Q000503:physiopathology*; D011972:Receptor, Insulin / Q000378:metabolism*; D012016:Reference Values
D001786:Blood Glucose; D007328:Insulin; D011972:Receptor, Insulin