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

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 o r lack of GLP-1 function. Exogenous GLP-1 is exquisitely effective in Type 2 diabetic patients, making receptor defects unlikely. GLP-1 responses afte r meals as detected by radioimmunoassay are not overtly reduced in Type 2 d iabetic patients. Therefore. a sequence analysis of exon 2 of the preproglu cagon gene coding for the GLP-1 protein was initiated in order to exclude p otential 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 muta tions of the GLP-1 sequence were identified, thus excluding mutations in th e GLP-1 sequence as a major contributor to the pathophysiological appearanc e of the Type 2 diabetic phenotype. Rare mutations, however, cannot be excl uded due to the small number of Type 2 diabetic patients examined.