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Mutant insulin syndromes.

A Vinik1, G Bell

  • 1Department of Medicine, University of Michigan, Ann Arbor.

Hormone and Metabolic Research = Hormon- Und Stoffwechselforschung = Hormones Et Metabolisme
|January 1, 1988
PubMed
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Abnormal insulin and proinsulin molecules can cause insulin resistance and diabetes. Identifying these molecular variants is crucial for understanding and managing these conditions.

Area of Science:

  • Endocrinology
  • Human Genetics
  • Molecular Biology

Background:

  • Recent advancements enable detailed characterization of circulating insulin species and human insulin gene isolation.
  • Abnormal insulin or proinsulin variants have been identified in several individuals.
  • These variants are linked to conditions like insulin resistance, diabetes, and autoimmune insulin syndrome.

Purpose of the Study:

  • To present a protocol for investigating subjects with potential mutant or abnormal insulin forms.
  • To highlight the clinical implications of abnormal insulin and proinsulin molecules.

Main Methods:

  • High-performance liquid chromatography (HPLC) for molecular characterization.
  • Recombinant DNA technology for gene isolation and analysis.

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Main Results:

  • Identified abnormal insulin variants such as [Leu B25], [Ser B24], and [Leu A3] insulin.
  • Observed clinical syndromes including endogenous insulin resistance with high insulin levels and high insulin/C-peptide ratio.
  • Found abnormal insulin forms in autoimmune insulin syndrome and reactive hypoglycemia, with potential autosomal dominant inheritance.

Conclusions:

  • Abnormal insulin and proinsulin molecules contribute to various clinical syndromes, including diabetes and hypoglycemia.
  • Investigating these molecular abnormalities is essential for diagnosis and understanding disease mechanisms.
  • Abnormal endogenous antigens may play a role in autoimmune responses, as suggested by autoimmune insulin syndrome.