[Various molecular mechanisms involved in the pathogenesis of type II diabetes and their potential therapeutic importance].
The pancreatic beta cell presents functional abnormalities in the early stages of development of non-insulin dependent diabetes mellitus (NIDDM). The disappearance of the first phase of insulin secretion induced by a glucose load is a early marker of NIDDM. This abnormality could be secondary to the low expression of the pancreatic glucose transporter GLUT2. Together with the glucokinase enzyme, GLUT2 is responsible for proper beta cell sensing of the extracellular glucose levels. In NIDDM, the GLUT2 mRNA levels are low, a fact which suggests a transcriptional defect of the GLUT2 gene. The first phase of glucose-induced insulin secretion by the beta pancreatic cell can be partly restored by the administration of a peptide discovered by a molecular approach, the glucagon-like peptide 1 (GLP-1). The gene encoding for the glucagon is expressed in a cell-specific manner in the A cells of the pancreatic islet and the L cells of the intestinal tract. The maturation process of the propeptide encoded by the glucagon gene is different in the two cells: the glucagon is the main hormone produced by the A cells whereas the glucagon-like peptide 1 (GLP-1) is the major peptide synthesized by the L cells of the intestine. GLP-1 is an incretin hormone and is at present the most potent insulinotropic peptide. The first results of the administration of GLP-1 to normal volunteers and diabetic patients are promising and may be a new therapeutic approach to treating diabetic patients.
Waeber
G
G
Département de médecine interne B, Centre hospitalier universitaire vaudois, Lausanne.
Nicod
P
P
D003924:Diabetes Mellitus, Type 2 / Q000235:genetics / Q000378:metabolism* / Q000628:therapy; D005934:Glucagon / Q000235:genetics / Q000627:therapeutic use; D052216:Glucagon-Like Peptide 1; D006801:Humans; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000378:metabolism; D009004:Monosaccharide Transport Proteins / Q000378:metabolism; D010446:Peptide Fragments / Q000235:genetics / Q000627:therapeutic use; D011498:Protein Precursors / Q000235:genetics / Q000627:therapeutic use; D012333:RNA, Messenger / Q000235:genetics; D014158:Transcription, Genetic
D007328:Insulin; D009004:Monosaccharide Transport Proteins; D010446:Peptide Fragments; D011498:Protein Precursors; D012333:RNA, Messenger; D052216:Glucagon-Like Peptide 1; D005934:Glucagon
Quelques mécanismes moléculaires impliqués dans la pathogenèse du diabète de type II et leur importance thérapeutique potentielle.