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Abstract:
In an attempt to determine whether the decreased number of insulin's receptors in obesity is a result of downregulation of the receptors, diazoxide (5 mg/kg/d) was given to 10 obese subjects. Insulin's suppression by diazoxide in these 10 subjects resulted in a mild glucose intolerance and an increase in insulin's receptors in seven of the 10 subjects. The subjects could be divided into three groups by analyzing the Scatchard plots of their insulin receptor studies before and after diazoxide. Four subjects exhibited an increase in both high affinity and low affinity receptors, three showed an increase only in high affinity receptors, and three failed to demonstrate any change in receptors in response to diazoxide. These studies support the concept that the decreased number of insulin's receptors observed in obesity is a result of the downregulation of the receptors and is not the primary, underlying cause of insulin resistance in obesity, although a contributory role cannot be ruled out.
Insights
Diazoxide treatment in obese individuals revealed that reduced insulin receptors are likely due to downregulation, not the primary cause of insulin resistance. Some subjects showed increased insulin receptor numbers after treatment.
Area of Science:
- Metabolism and Endocrinology
- Molecular Biology
Background:
- Obesity is often associated with insulin resistance and a decreased number of insulin receptors.
- The precise mechanism behind reduced insulin receptor numbers in obesity remains under investigation, with receptor downregulation being a key hypothesis.
Purpose of the Study:
- To investigate whether the diminished insulin receptor count in obese individuals is a consequence of receptor downregulation.
- To assess the impact of pharmacologically suppressing insulin levels on insulin receptor numbers and glucose tolerance.
Main Methods:
- Diazoxide was administered at 5 mg/kg/d to 10 obese subjects.
- Insulin receptor studies were conducted using Scatchard plot analysis before and after diazoxide treatment.
- Changes in both high-affinity and low-affinity insulin receptors were evaluated.
Main Results:
- Diazoxide administration led to mild glucose intolerance and an increase in insulin receptors in 7 out of 10 subjects.
- Subjects were categorized into three groups based on receptor response: increased high and low affinity receptors (4 subjects), increased high-affinity receptors only (3 subjects), and no change (3 subjects).
Conclusions:
- The findings support the hypothesis that reduced insulin receptor numbers in obesity result from receptor downregulation.
- Receptor downregulation is suggested to be a consequence rather than the primary cause of insulin resistance in obesity, though it may contribute.
- Individual variations in receptor response to insulin suppression were observed.