Lack of germline mutations in the preproglucagon gene region coding for glucagon-like peptide 1 in Type 2 diabetic (NIDDM) patients.

Abstract

Glucagon-like peptide 1 (GLP-1) has antidiabetic effects and many facets of Type 2 diabetes could theoretically be the consequence of a reduction in or lack of GLP-1 function. Exogenous GLP-1 is exquisitely effective in Type 2 diabetic patients, making receptor defects unlikely. GLP-1 responses after meals as detected by radioimmunoassay are not overtly reduced in Type 2 diabetic patients. Therefore, a sequence analysis of exon 2 of the preproglucagon gene coding for the GLP-1 protein was initiated in order to exclude potential germline mutations. 24 Type 2 diabetic patients and in 14 control subjects with normal oral glucose tolerance (WHO criteria) were studied. In all specimens of peripheral blood leukocyte DNA examined, no germline mutations of the GLP-1 sequence were identified, thus excluding mutations in the GLP-1 sequence as a major contributor to the pathophysiological appearance of the Type 2 diabetic phenotype. Rare mutations, however, cannot be excluded due to the small number of Type 2 diabetic patients examined.

• Authors: M Nauck, S Hahn, A Sauerwald, W Schmiegel
• Journal: Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association (Exp Clin Endocrinol Diabetes) Vol. 108 Issue 2 Pg. 72-5 ( 2000) ISSN: 0947-7349 [Print] Germany
• PMID: 10826511 (Publication Type: Journal Article)

Chemical References

• Insulin
• Peptide Fragments
• Protein Precursors
• Proglucagon
• Glucagon-Like Peptide 1
• Glucagon

Topics

• Aged
• Amino Acid Sequence
• Base Sequence
• Diabetes Mellitus, Type 2 (genetics, physiopathology)
• Female
• Glucagon (chemistry, genetics, pharmacology)
• Glucagon-Like Peptide 1
• Humans
• Insulin (metabolism)
• Insulin Secretion
• Male
• Middle Aged
• Molecular Sequence Data
• Mutation
• Peptide Fragments (chemistry, genetics, pharmacology)
• Proglucagon
• Protein Precursors (chemistry, genetics, pharmacology)
• Sequence Analysis, DNA